Genetic Diversity Based on LipL32, 16S rRNA and ColA Expression in Leptospira spp. Isolated From Rodent Hosts in Samarahan and Gedong Districts in Sarawak

Genetic Diversity Based on LipL32, 16S rRNA and ColA Expression in Leptospira spp. Isolated From Rodent Hosts in Samarahan and Gedong Districts in Sarawak

Leptospirosis is a major zoonotic disease in the world that is caused by Leptospira spp., that may cause acute febrile illness in mammals with varied pathogenicity and clinical disease. Among factors that have been associated with pathogenicity of Leptopsira are LipL32 and ColA gene. LipL32 has been...

Full description

Saved in:
Bibliographic Details
Main Author: Mohamed Nur Azim, Mazlan
Format: Thesis
Language:English
Published: 2022
Subjects:
QR Microbiology
R Medicine (General)
Online Access:http://ir.unimas.my/id/eprint/40246/6/Thesis%20PhD_Mohamed%20Nur%20Azim%20bin%20Mazlan-%20fulltext.pdf
Tags: Add Tag
No Tags, Be the first to tag this record!
id my-unimas-ir.40246
record_format uketd_dc
institution Universiti Malaysia Sarawak
collection UNIMAS Institutional Repository
language English
topic QR Microbiology
R Medicine (General)
QR Microbiology
spellingShingle QR Microbiology
R Medicine (General)
QR Microbiology
Mohamed Nur Azim, Mazlan
Genetic Diversity Based on LipL32, 16S rRNA and ColA Expression in Leptospira spp. Isolated From Rodent Hosts in Samarahan and Gedong Districts in Sarawak
description Leptospirosis is a major zoonotic disease in the world that is caused by Leptospira spp., that may cause acute febrile illness in mammals with varied pathogenicity and clinical disease. Among factors that have been associated with pathogenicity of Leptopsira are LipL32 and ColA gene. LipL32 has been identified to play an important role in TLR-dependent pathway and inducing erythrocytes. ColA (LA0872), a gene coding for bacterial collagenase, a common invasive enzyme which facilitates the leptospires to quickly invade and spread into internal organs. Gene or protein that had been expressed by leptospires during infection or within specific host may provide glimpses into leptospiral pathogenic strategies. The study was conducted in Samarahan Division, Sarawak involving two locations; Kota Samarahan and Gedong. Traps were set at the study sites and 31 rodents were caught with 96.7% of them are from Rattus rattus species. The kidneys and blood samples were cultured into Ellinghausen-McCullough-Johnson-Harris (EMJH) media added with 5-fluorouracil. DNA and protein isolates from positive cultures were extracted and analysed. From the 31 kidney samples of rodents caught, 28 kidney tissue samples (90.3%) showed presence of leptospire-like organism in cultures. PCR analyses utilizing 16S gene primers confirmed the presence of leptospires, in 90.3% of rodents caught in the study area. Almost half of the leptospires detected were saprophytic (45.2%) and pathogenic Leptospira spp. (38.7%). The highest number of species detected was pathogenic Leptospira, Leptospira kmetyi strain SS-S7 with 38.7%, from the whole isolates sequenced when compared to GenBank, followed by, intermediate Leptospira, Leptospira wolfii strain SS-S17 detected (12.9%), and saprophytic Leptospira, Leptospira biflexa strain Patoc_DB58 (19.4%), Leptospira wolbachii serovar Codice strain and Leptospira idonii strain Eri-1 16S ribosomal RNA (6.5% respectively) and Leptospira terpestrae serovar Hualin strain LT 11-33 (16.1%). There were no related DNA sequences retrieved from LipL32 primers after multiple passages of cultures. The DNA sequence degree of homology was varied from 80% to 99% which were clustered into 3 clusters (A1, A2 and A3). Most of the isolates were delineated into cluster A2 with 15 isolates (48.4%) which is close to NR.043043.1 sequence retrieved from NCBI database, followed by A1 cluster with 11 isolates (35.5%) (KY411405.1), and A3 cluster with 4 isolates (12.9%) (KY411411.1). All samples that shown presence of collagenase was belong to cluster A2. Interestingly, ColA protein was not detected in all intermediate and saphrophytic isolates and only detected in eight of the samples (25.8%) which only infected with pathogenic strain, Leptospira kmetyi. The findings indicated that a high proportion of rodents in the study area were infected with Leptospira spp. and about a third of them were harboured with pathogenic strain, Leptospira kmetyi. It is found that ColA gene was expressed only in pathogenic leptospires, and might indicate its importance in the pathogenesis of pathogenic Leptospira spp. in rodent hosts.
format Thesis
qualification_name Doctor of Philosophy (PhD.)
qualification_level Doctorate
author Mohamed Nur Azim, Mazlan
author_facet Mohamed Nur Azim, Mazlan
author_sort Mohamed Nur Azim, Mazlan
title Genetic Diversity Based on LipL32, 16S rRNA and ColA Expression in Leptospira spp. Isolated From Rodent Hosts in Samarahan and Gedong Districts in Sarawak
title_short Genetic Diversity Based on LipL32, 16S rRNA and ColA Expression in Leptospira spp. Isolated From Rodent Hosts in Samarahan and Gedong Districts in Sarawak
title_full Genetic Diversity Based on LipL32, 16S rRNA and ColA Expression in Leptospira spp. Isolated From Rodent Hosts in Samarahan and Gedong Districts in Sarawak
title_fullStr Genetic Diversity Based on LipL32, 16S rRNA and ColA Expression in Leptospira spp. Isolated From Rodent Hosts in Samarahan and Gedong Districts in Sarawak
title_full_unstemmed Genetic Diversity Based on LipL32, 16S rRNA and ColA Expression in Leptospira spp. Isolated From Rodent Hosts in Samarahan and Gedong Districts in Sarawak
title_sort genetic diversity based on lipl32, 16s rrna and cola expression in leptospira spp. isolated from rodent hosts in samarahan and gedong districts in sarawak
granting_institution Universiti Malaysia Sarawak
granting_department Fakulti Perubatan Dan Sains Kesihatan
publishDate 2022
url http://ir.unimas.my/id/eprint/40246/6/Thesis%20PhD_Mohamed%20Nur%20Azim%20bin%20Mazlan-%20fulltext.pdf
_version_ 1783728521572515840
spelling my-unimas-ir.402462023-03-17T03:28:21Z Genetic Diversity Based on LipL32, 16S rRNA and ColA Expression in Leptospira spp. Isolated From Rodent Hosts in Samarahan and Gedong Districts in Sarawak 2022 Mohamed Nur Azim, Mazlan QR Microbiology R Medicine (General) RA0421 Public health. Hygiene. Preventive Medicine Leptospirosis is a major zoonotic disease in the world that is caused by Leptospira spp., that may cause acute febrile illness in mammals with varied pathogenicity and clinical disease. Among factors that have been associated with pathogenicity of Leptopsira are LipL32 and ColA gene. LipL32 has been identified to play an important role in TLR-dependent pathway and inducing erythrocytes. ColA (LA0872), a gene coding for bacterial collagenase, a common invasive enzyme which facilitates the leptospires to quickly invade and spread into internal organs. Gene or protein that had been expressed by leptospires during infection or within specific host may provide glimpses into leptospiral pathogenic strategies. The study was conducted in Samarahan Division, Sarawak involving two locations; Kota Samarahan and Gedong. Traps were set at the study sites and 31 rodents were caught with 96.7% of them are from Rattus rattus species. The kidneys and blood samples were cultured into Ellinghausen-McCullough-Johnson-Harris (EMJH) media added with 5-fluorouracil. DNA and protein isolates from positive cultures were extracted and analysed. From the 31 kidney samples of rodents caught, 28 kidney tissue samples (90.3%) showed presence of leptospire-like organism in cultures. PCR analyses utilizing 16S gene primers confirmed the presence of leptospires, in 90.3% of rodents caught in the study area. Almost half of the leptospires detected were saprophytic (45.2%) and pathogenic Leptospira spp. (38.7%). The highest number of species detected was pathogenic Leptospira, Leptospira kmetyi strain SS-S7 with 38.7%, from the whole isolates sequenced when compared to GenBank, followed by, intermediate Leptospira, Leptospira wolfii strain SS-S17 detected (12.9%), and saprophytic Leptospira, Leptospira biflexa strain Patoc_DB58 (19.4%), Leptospira wolbachii serovar Codice strain and Leptospira idonii strain Eri-1 16S ribosomal RNA (6.5% respectively) and Leptospira terpestrae serovar Hualin strain LT 11-33 (16.1%). There were no related DNA sequences retrieved from LipL32 primers after multiple passages of cultures. The DNA sequence degree of homology was varied from 80% to 99% which were clustered into 3 clusters (A1, A2 and A3). Most of the isolates were delineated into cluster A2 with 15 isolates (48.4%) which is close to NR.043043.1 sequence retrieved from NCBI database, followed by A1 cluster with 11 isolates (35.5%) (KY411405.1), and A3 cluster with 4 isolates (12.9%) (KY411411.1). All samples that shown presence of collagenase was belong to cluster A2. Interestingly, ColA protein was not detected in all intermediate and saphrophytic isolates and only detected in eight of the samples (25.8%) which only infected with pathogenic strain, Leptospira kmetyi. The findings indicated that a high proportion of rodents in the study area were infected with Leptospira spp. and about a third of them were harboured with pathogenic strain, Leptospira kmetyi. It is found that ColA gene was expressed only in pathogenic leptospires, and might indicate its importance in the pathogenesis of pathogenic Leptospira spp. in rodent hosts. Universiti Malaysia Sarawak 2022 Thesis http://ir.unimas.my/id/eprint/40246/ http://ir.unimas.my/id/eprint/40246/6/Thesis%20PhD_Mohamed%20Nur%20Azim%20bin%20Mazlan-%20fulltext.pdf text en validuser phd doctoral Universiti Malaysia Sarawak Fakulti Perubatan Dan Sains Kesihatan Adler, B. (2015). Leptospira and Leptospirosis (1 ed.). Springer-Verlag Berlin Heidelberg. https://doi.org/10.1007/978-3-662-45059-8. Adler, B., & de la Pena Moctezuma, A. (2010). Leptospira and leptospirosis. Veterinary Microbiology, 140(3-4), 287-296. https://doi.org/10.1016/j.vetmic.2009.03.012. Adler, B., & Faine, S. (1977). Host immunological mechanisms in the resistance of mice to leptospiral infections. Infection and Immunity, 17(1), 67-72. Adler, B., Lo, M., Seemann, T., & Murray, G. L. (2011). Pathogenesis of leptospirosis: the influence of genomics. Veterinary Microbiology, 153(1-2), 73-81. https://doi.org/10.1016/j.vetmic.2011.02.055. Agudelo-Florez, P., Londono, A. F., Quiroz, V. H., Angel, J. C., Moreno, N., Loaiza, E. T., Munoz, L. F., & Rodas, J. D. (2009). Prevalence of Leptospira spp. in urban rodents from a groceries trade center of Medellin, Colombia. American Journal of Tropical Medicine and Hygiene, 81(5), 906-910. https://doi.org/81/5/906 [pii] 10.4269/ajtmh.2009.09-0195. Alexander, A., Baer, A., Fair, J. R., Gochenour, W. S., Jr., King, J. H., Jr., & Yager, R. H. (1952). Leptospiral uveitis; report of a bacteriologically verified case. AMA Archieve of Ophthalmology, 48(3), 292-297. Alexander, A. D. (1986). Serological diagnosis of leptospirosis . In N. R. Rose, H. Friedman, & J. L. Fahey (Eds.), Manual of Clinical Laboratory Immunology (3 ed.). American Society for Microbiology. Alston, J. M., & Broom, J. C. (1958). Leptospirosis: In Man and Animals. Livingstone. Amutha, R., Chaudhury, P., Garg, A. P., Vasan, P., Cheema, P. S., & Srivastava, S. K. (2007). Cloning and sequence analysis of the gene encoding LipL32 of Leptospira interrogans serovar Sejroe. Veterinary Research Communication, 31(5), 513-519. https://doi.org/10.1007/s11259-007-3533-3. Anderson, D. C., Folland, D. S., Fox, M. D., Patton, C. M., & Kaufmann, A. F. (1978). Leptospirosis: a common-source outbreak due to leptospires of the grippotyphosa serogroup. American Journal of Epidemiology, 107(6), 538-544. Anderson, J. F., Miller, D. A., Post, J. E., Johnson, R. C., Magnarelli, L. A., & Andreadis, T. G. (1993). Isolation of Leptospira interrogans serovar grippotyphosa from the skin of a dog. American Veterinary Medical Association, 203(11), 1550-1551. Andrade, L., Rodrigues, A. C., Jr., Sanches, T. R., Souza, R. B., & Seguro, A. C. (2007). Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung. American Journal of Physiology-Renal Physiology, 292(2), F586-592. https://doi.org/10.1152/ajprenal.00102.2006. Arean, V. M. (1962). The pathologic anatomy and pathogenesis of fatal human leptospirosis (Weil's disease). American Journal of Pathology, 40, 393-423. Artiushin, S. C., Timoney, J. F., Balasuriya, U. B., Erol, E., & Sells, S. F. (2012). Real-time PCR for detection of Leptospira interrogans serovar Pomona type kennewicki in equine clinical specimens. Journal of Equine Veterinary Science, 32(10, Supplement), S53. https://doi.org/https://doi.org/10.1016/j.jevs.2012.08.117. Athanazio, D. A., Silva, E. F., Santos, C. S., Rocha, G. M., Vannier-Santos, M. A., McBride, A. J., Ko, A. I., & Reis, M. G. (2008). Rattus norvegicus as a model for persistent renal colonization by pathogenic Leptospira interrogans. Acta Tropica, 105(2), 176-180. https://doi.org/10.1016/j.actatropica.2007.10.012. Au - Beeton, C., Au - Garcia, A., & Au - Chandy, K. G. (2007). Drawing blood from rats through the saphenous vein and by cardiac puncture. JoVE(7), e266. https://doi.org/doi:10.3791/266. Australia Wildlife Conservancy. (2013). An otographing guidelines. Retrieved 31 August 2017 from https://www.environment.gov.au/system/files/pages/a8cac765-28ca-4da4-9195-9069626f04a1/files/e2016-0120-application-attachment-handling-guidelines.pdf. Awad, M. M., Ellemor, D. M., Bryant, A. E., Matsushita, O., Boyd, R. L., Stevens, D. L., Emmins, J. J., & Rood, J. I. (2000). Construction and virulence testing of a collagenase mutant of Clostridium perfringens. Microbial Pathogenesis, 28(2), 107-117. https://doi.org/10.1006/mpat.1999.0328. Bahaman, A. R., Ibrahim, A. L., & Adam, H. (1987). Serological prevalence of leptospiral infection in domestic animals in West Malaysia. Epidemiology and Infection, 99(2), 379-392. Balamurugan, V., Gangadhar, N. L., Mohandoss, N., Thirumalesh, S. R., Dhar, M., Shome, R., Krishnamoorthy, P., Prabhudas, K., & Rahman, H. (2013). Characterization of Leptospira isolates from animals and humans: phylogenetic analysis identifies the prevalence of intermediate species in India. Springerplus, 2, 362. https://doi.org/10.1186/2193-1801-2-362. Bao, L., & Dai, B. (1990). [Detection of the microquantity DNA of Leptospira interrogans by polymerase chain reaction]. Hua Xi Yi Ke Da Xue Xue Bao, 21(3), 225-229. Barcellos, C., & Sabroza, P. C. (2001). The place behind the case: leptospirosis risks and associated environmental conditions in a flood-related outbreak in Rio de Janeiro. Cadernos de Saude Publica, 17, S59-S67 Baskerville, A., Conlan, J. W., Ashworth, L. A., & Dowsett, A. B. (1986). Pulmonary damage caused by a protease from Legionella pneumophila. British Journal of Experimental Pathology, 67, 527-536. Battey, Y. M., Smith, D. J., & Barrow, G. J. (1964). The Epidemiology of Leptospirosis in North Queensland. Ii. Further Observations on the Hosts in the Mossman District. Journal of Hygiene (Lond), 62, 485-494. Benacer, D., Mohd Zain, S. N., Amran, F., Galloway, R. L., & Thong, K. L. (2013). Isolation and molecular characterization of Leptospira interrogans and Leptospira borgpetersenii isolates from the urban rat populations of Kuala Lumpur, Malaysia. American Journal of Tropical Medicine and Hygiene, 88(4), 704-709. https://doi.org/ajtmh.12-0662 [pii]10.4269/ajtmh.12-0662. Benacer, D., Mohd Zain, S. N., Sim, S. Z., Mohd Khalid, M. K., Galloway, R. L., Souris, M., & Thong, K. L. (2016). Determination of Leptospira borgpetersenii serovar Javanica and Leptospira interrogans serovar Bataviae as the persistent Leptospira serovars circulating in the urban rat populations in Peninsular Malaysia. Parasite Vectors, 9, 117. https://doi.org/10.1186/s13071-016-1400-1. Benacer, D., Thong, K. L., Verasahib, K. B., Galloway, R. L., Hartskeerl, R. A., Lewis, J. W., & Mohd Zain, S. N. (2016). Human leptospirosis in malaysia: reviewing the challenges after 8 decades (1925-2012). Asia Pacific Journal of Public Health, 28(4), 290-302. https://doi.org/10.1177/1010539516640350. Benacer, D., Woh, P. Y., Mohd Zain, S. N., Amran, F., & Thong, K. L. (2013). Pathogenic and saprophytic Leptospira species in water and soils from selected urban sites in peninsular Malaysia. Microbes and Environments, 28(1), 135-140. https://doi.org/DN/JST.JSTAGE/jsme2/ME12154. Berg, H. C., Bromley, D. B., & Charon, N. W. (1978). Leptospiral motility. In R. Y. Stanier, H. J. Rogers, & J. B. Ward (Eds.), Relations between structure and function in the prokaryotic cell. 28th Symposium of the Society for General Microbiology. (28 ed., pp. 285-294). Cambridge University Press. Bharti, A.R., Nally, J.E., Ricaldi, J.N., Matthias, M.A., Diaz, M.M. (2003). Leptospirosis: a zoonotic disease of global importance. Lancet Infectious Disease, 3, 757–771. Birnbaum, S., Shenberg, E., & Torten, M. (1972). The influence of maternal antibodies on the epidemiology of leptospiral carrier state in mice. American Journal of Epidemiology, 96(4), 313-317. Birnbaum, S., Torten, M., & Shenberg, E. (1974). Experimental evidence for a cyclic occurrence of leptospirosis in vector mice. American Journal of Epidemiology, 99(3), 225-229. Blasdell, K. R., Morand, S., Perera, D., & Firth, C. (2019). Association of rodent-borne Leptospira spp. with urban environments in Malaysian Borneo. PLoS Neglected Tropical Diseases, 13(2), e0007141. https://doi.org/10.1371/journal.pntd.0007141. Bolin, C. A., Zuerner, R. L., & Trueba, G. (1989). Comparison of three techniques to detect Leptospira interrogans serovar hardjo type hardjo-bovis in bovine urine. American Journal of Veterinary Research, 50(7), 1001-1003. Bond, M. D., & Van Wart, H. E. (1984a). Characterization of the individual collagenases from Clostridium histolyticum. Biochemistry, 23(13), 3085-3091. Bond, M. D., & Van Wart, H. E. (1984b). Purification and separation of individual collagenases of Clostridium histolyticum using red dye ligand chromatography. Biochemistry, 23(13), 3077-3085. Bond, M. D., & Van Wart, H. E. (1984c). Relationship between the individual collagenases of Clostridium histolyticum: evidence for evolution by gene duplication. Biochemistry, 23(13), 3092-3099. Boonyod, D., Poovorawan, Y., Bhattarakosol, P., & Chirathaworn, C. (2005). LipL32, an outer membrane protein of Leptospira, as an antigen in a dipstick assay for diagnosis of leptospirosis. Asian Pacific Journal of Allergy and Immunology, 23(2-3), 133-141. Boonsilp, S., Thaipadungpanit, J., Amornchai, P., Wuthiekanun, V., Chierakul, W., Limmathurotsakul, D., Day, N.P. and Peacock, S.J. (2011). Molecular detection and speciation of pathogenic Leptospira spp. in blood from patients with culture-negative leptospirosis. BMC Infectious Diseases, 11(1), 1-9. Bosman, F. T., & Stamenkovic, I. (2003). Functional structure and composition of the extracellular matrix. Journal of Pathology, 200(4), 423-428. https://doi.org/10.1002/path.1437. Bourhy, P., Herrmann Storck, C., Theodose, R., Olive, C., Nicolas, M., Hochedez, P., Lamaury, I., Zinini, F., Bremont, S., Landier, A., Cassadou, S., Rosine, J., & Picardeau, M. (2013). Serovar diversity of pathogenic Leptospira circulating in the French West Indies. PLoS Neglected Tropical Diseases, 7(3), e2114. https://doi.org/10.1371/journal.pntd.0002114. Brenner, D. J., Kaufmann, A. F., Sulzer, K. R., Steigerwalt, A. G., Rogers, F. C., & Weyant, R. S. (1999). Further determination of DNA relatedness between serogroups and serovars in the family Leptospiraceae with a proposal for Leptospira alexanderi sp. nov. and four new Leptospira genomospecies. International Journal of Systematic and Evolutionary Microbiology, 49 Pt 2, 839-858. https://doi.org/10.1099/00207713-49-2-839. Bruggemann, H., Baumer, S., Fricke, W. F., Wiezer, A., Liesegang, H., Decker, I., Herzberg, C., Martinez-Arias, R., Merkl, R., Henne, A., & Gottschalk, G. (2003). The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Proceedings of the National Academy of Science of the United States of America, 100(3), 1316-1321. https://doi.org/10.1073/pnas.0335853100. Budihal, S. V., & Perwez, K. (2014). Leptospirosis diagnosis: competancy of various laboratory tests. Journal of clinical and diagnostic research: JCDR, 8(1), 199. Bulach, D. M., Zuerner, R. L., Wilson, P., Seemann, T., McGrath, A., Cullen, P. A., Davis, J., Johnson, M., Kuczek, E., Alt, D. P., Peterson-Burch, B., Coppel, R. L., Rood, J. I., Davies, J. K., & Adler, B. (2006). Genome reduction in Leptospira borgpetersenii reflects limited transmission potential. Proceedings of the National Academy of Science of the United States of America, 103(39), 14560-14565. https://doi.org/10.1073/pnas.0603979103. Caldas, E. M., Sampaio, M. B., Costa, E., & Tishcenko, L. M. (1978). Patoc 1 and Rufino strains of Leptospira biflexa, as screening antigens in the diagnosis of leptospirosis. International Journal of Zoonoses, 5(2), 91-96. Carleton, O., Charon, N. W., Allender, P., & O'Brien, S. (1979). Helix handedness of Leptospira interrogans as determined by scanning electron microscopy. Journal of Bacteriology, 137(3), 1413-1416. Carter, M. E., & Cordes, D. O. (1980). Leptospirosis and other infections of Rattus rattus and Rattus norvegicus. New Zealand Veterinary Journal, 28(3), 45-50. https://doi.org/10.1080/00480169.1980.34688. CDC (2018, January 30). Leptospirosis: Fact sheet for clinicians. https://www.cdc.gov/leptospirosis/ Centers for Disease Control and Prevention. (1998). Outbreak of acute febrile illness among athletes participating in triathlons-Wisconsin and Illinois, 1998. Morbidity and Mortality Weekly Report, 47, 816-817. Cetinkaya, B., Ertas, H., Ongor, H., & Muz, A. (2000). Detection of Leptospira Species by Polymerase Chain Reaction (PCR) in Urine of Cattle (Vol. 24). Chakraborty, A., Miyahara, S., Villanueva, S. Y., Saito, M., Gloriani, N. G., & Yoshida, S. (2011). A novel combination of selective agents for isolation of Leptospira species. Microbiology and Immunology, 55(7), 494-501. https://doi.org/10.1111/j.1348-0421.2011.00347. Chang, M. Y., Cheng, Y. C., Hsu, S. H., Ma, T. L., Chou, L. F., Hsu, H. H., Tian, Y. C., Chen, Y. C., Sun, Y. J., Hung, C. C., Pan, R. L., & Yang, C. W. (2016). Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae. Scientific Reports, 6, 27838. https://doi.org/10.1038/srep27838. Chassin, C., Picardeau, M., Goujon, J. M., Bourhy, P., Quellard, N., Darche, S., Badell, E., d'Andon, M. F., Winter, N., Lacroix-Lamande, S., Buzoni-Gatel, D., Vandewalle, A., & Werts, C. (2009). TLR4- and TLR2-mediated B cell responses control the clearance of the bacterial pathogen, Leptospira interrogans. Journal of Immunology, 183(4), 2669-2677. https://doi.org/10.4049/jimmunol.0900506. Choi, J. S., Ha, Y. M., Joo, C. U., Cho, K. K., Kim, S. J., & Choi, I. S. (2012). Inhibition of oral pathogens and collagenase activity by seaweed extracts. Journal of Environment Biology, 33(1), 115-121. Chou, T. Y., & Prabhu, S. P. (2011). Clinical course and management of postoperative methicillin-resistant Staphylococcus aureus keratitis in immunocompromised patients: two case reports. Clinical Ophthalmology, 5, 1789-1793. https://doi.org/10.2147/OPTH.S23201. Choy, H. A., Kelley, M. M., Chen, T. L., Moller, A. K., Matsunaga, J., & Haake, D. A. (2007). Physiological osmotic induction of Leptospira interrogans adhesion: LigA and LigB bind extracellular matrix proteins and fibrinogen. Infection and Immunity, 75(5), 2441-2450. https://doi.org/10.1128/IAI.01635-06. Cole, J. R., Jr., Sulzer, C. R., & Pursell, A. R. (1973). Improved microtechnique for the leptospiral microscopic agglutination test. Applied Microbiology, 25(6), 976-980. Collares-Pereira, M., Korver, H., Cao Thi, B. V., Santos-Reis, M., Bellenger, E., Baranton, G., & Terpstra, W. J. (2000). Analysis of Leptospira isolates from mainland Portugal and the Azores islands. FEMS Microbiology Letters, 185(2), 181-187. Collares-Pereira, M., Mathias, M. L., Santos-Reis, M., Ramalhinho, M. G., & Duarte-Rodrigues, P. (2000). Rodents and Leptospira transmission risk in Terceira island (Azores). European Jounal of Epidemiology, 16(12), 1151-1157. Cook, D. N., Pisetsky, D. S., & Schwartz, D. A. (2004). Toll-like receptors in the pathogenesis of human disease. Nature Immunology, 5(10), 975-979. Corwin, A., Ryan, A., Bloys, W., Thomas, R., Deniega, B., & Watts, D. (1990). A waterborne outbreak of leptospirosis among United States military personnel in Okinawa, Japan. International Journal of Epidemiology, 19(3), 743-748. Cosson, J. F., Picardeau, M., Mielcarek, M., Tatard, C., Chaval, Y., Suputtamongkol, Y., Buchy, P., Jittapalapong, S., Herbreteau, V., & Morand, S. (2014). Epidemiology of Leptospira transmitted by rodents in southeast Asia. PLoS Neglected Tropical Diseases, 8(6), e2902. https://doi.org/10.1371/journal.pntd.0002902. Costa, F., Hagan, J. E., Calcagno, J., Kane, M., Torgerson, P., Martinez-Silveira, M. S., Stein, C., Abela-Ridder, B., & Ko, A. I. (2015). Global morbidity and mortality of leptospirosis: a systematic review. PLoS Neglected Tropical Diseases, 9(9), e0003898. Costa, F., Wunder Jr, E. A., De Oliveira, D., Bisht, V., Rodrigues, G., Reis, M. G., ... & Childs, J. E. (2015). Patterns in Leptospira shedding in Norway rats (Rattus norvegicus) from Brazilian slum communities at high risk of disease transmission. PLoS Neglected Tropical Diseases, 9(6), e0003819. Croda, J., Figueira, C. P., Wunder, E. A., Jr., Santos, C. S., Reis, M. G., Ko, A. I., & Picardeau, M. (2008). Targeted mutagenesis in pathogenic Leptospira species: disruption of the LigB gene does not affect virulence in animal models of leptospirosis. Infection and Immunity, 76(12), 5826-5833. https://doi.org/10.1128/IAI.00989-08. Crump, J.A., Morrissey, A.B., Nicholson, W.L., Massung, R.F., Stoddard, R.A., Galloway, R.L., Ooi, E.E., Maro, V.P., Saganda, W., Kinabo, G.D. and Muiruri, C. (2013). Etiology of severe non-malaria febrile illness in Northern Tanzania: a prospective cohort study. PLoS neglected tropical diseases, 7(7), e2324. Cullen, P., Xu, X., Matsunaga, J., Sanchez, Y., Ko, A., Haake, D., & Adler, B. (2005). Surfaceome of Leptospira spp. Infection and Immunity, 73(8), 4853-4863. Cullen, P. A., Haake, D. A., Bulach, D. M., Zuerner, R. L., & Adler, B. (2003). LipL21 is a novel surface-exposed lipoprotein of pathogenic Leptospira species. Infection and Immunity, 71(5), 2414-2421. Cvetnic, Z., Margaletić, J., Toncic, J., Turk, N., Milas, Z., Spicic, S., Lojkic, M., Terzic, S., Jemersic, L., Humski, A., Mitak, M., Habrun, B., & Krt, B. (2003). A serological survey and isolation of leptospires from small rodents and wild boars in the Republic of Croatia (Vol. 48). Veterinary Medicine, https://doi.org/10.17221/5786. De Paepe, A., & Malfait, F. (2004). Bleeding and bruising in patients with Ehlers-Danlos syndrome and other collagen vascular disorders. British Journal of Haematology, 127(5), 491-500. https://doi.org/10.1111/j.1365-2141.2004.05220. Department of Statistics Malaysia. (2011). Population Distribution by Local Authority Areas and Mukims 2010. Department of Statistics Malaysia. Desvars, A., Jégo, S., Chiroleu, F., Bourhy, P., Cardinale, E., & Michault, A. (2011). Seasonality of human leptospirosis in Reunion Island (Indian Ocean) and its association with meteorological data. PloS one, 6(5), e20377. Diener, B., Carrick, J. L., & Berk, R. S. (1973). In vivo studies with collagenase from Pseudomonas aeruginosa. Infection and Immunity, 7, 212-217. Dikken, H., Kmety, E., de Geus, A., Adinarayanan, N., & Timmer, V. E. (1978). Two new Leptospira serovars belonging to the Hebdomadis serogroup. Tropical and Geographical Medicine, 30(4), 537-542. Doxey, A. C., Lynch, M. D. J., Müller, K. M., Meiering, E. M., & McConkey, B. J. (2008). Insights into the evolutionary origins of clostridial neurotoxins from analysis of the Clostridium botulinum strain A neurotoxin gene cluster. BMC Evolutionary Biology, 8(1), 316. https://doi.org/10.1186/1471-2148-8-316. Duarte, A. S., Correia, A., & Esteves, A. C. (2016). Bacterial collagenases - A review. Critical Reviews in Microbiology, 42(1), 106-126. https://doi.org/10.3109/1040841X.2014.904270. Dunn, M.J. (1993). Gel electrophoresis of proteins. Abingdon Oxford, United Kingdom. BIOS Scientific Publishers Ltd. Eckhard, U., Schonauer, E., Ducka, P., Briza, P., Nuss, D., & Brandstetter, H. (2009). Biochemical characterization of the catalytic domains of three different Clostridial collagenases. Biological Chemistry, 390(1), 11-18. https://doi.org/10.1515/BC.2009.004. Eckhard, U., Schonauer, E., Nuss, D., & Brandstetter, H. (2011). Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis. Nature Structural and Molecular Biology, 18(10), 1109-1114. https://doi.org/10.1038/nsmb.2127. El Jalii, I. M., & Bahaman, A. R. (2004). A review of human leptospirosis in Malaysia. Tropical Biomedicine, 21(2), 113-119. Elian, M., & Nicoara, I. (1964). The use of Leptospira biflexa patoc antigen in field investigations of leptospirosis. Bulletin World Health Organization, 31, 359-363. Ellinghausen, H. C., & McCullough, W. G. (1965). Nutrition of Leptospira pomona and growth of 13 other serotypes: A serumfree medium employing oleic acid albumin complex. American Journal of Veterinary Research, 26, 39-44. Ellis, W. A., Hovind-Hougen, K., Moller, S., & Birch-Andresen, A. (1983). Morphological changes upon subculturing of freshly isolated strains of Leptospira interrogans serovar hardjo. Zentralblatt für Bakteriologie, Mikrobiologie, und Hygiene, 255(2-3), 323-335. Ellis, W. A., McParland, P. J., Bryson, D. G., Thiermann, A. B., & Montgomery, J. (1986). Isolation of leptospires from the genital tract and kidneys of aborted sows. Veterinary Record, 118(11), 294-295. Ellis, W. A., Montgomery, J., & Cassells, J. A. (1985). Dihydrostreptomycin treatment of bovine carriers of Leptospira interrogans serovar hardjo. Research in Veterinary Science, 39(3), 292-295. Ellis, W. A., O'Brien, J. J., Neill, S. D., Ferguson, H. W., & Hanna, J. (1982). Bovine leptospirosis: microbiological and serological findings in aborted fetuses. Veterinary Record, 110(7), 147-150. Ellis, W. A., & Thiermann, A. B. (1986). Isolation of Leptospira interrogans serovar bratislava from sows in Iowa. American Journal of Veterinary Research, 47(7), 1458-1460. Ellis, W. A. (2015). Animal leptospirosis. Leptospira and leptospirosis, 99-137. Emanuel, M. L., Mackerras, I. M., & Smith, D. J. (1964). The Epidemiology of Leptospirosis in North Queensland. I. General Surgery of Animal Hosts. Journal of Hygiene (Lond), 62, 451-484. Erni, R., Rossell, M. D., Kisielowski, C., & Dahmen, U. (2009). Atomic-Resolution Imaging with a sub-50-pm eectron probe. Physical Review Letters, 102(9), 096101. https://doi.org/10.1103/PhysRevLett.102.096101. Escandón-Vargas, K., Osorio, L., & Astudillo-Hernández, M. (2017). Seroprevalence and factors associated with Leptospira infection in an urban district of Cali, Colombia. Cadernos de saude publica, 33, e00039216. Evangelista, K. V., & Coburn, J. (2010). Leptospira as an emerging pathogen: a review of its biology, pathogenesis and host immune responses. Future Microbiology, 5(9), 1413-1425. https://doi.org/10.2217/fmb.10.102. Faine, S. (1964). Reticuloendothelial phagocytosis of virulent leptospires. American Journal of Veterinary Research, 25, 830-835. Faine, S. (1982). Guidelines for the control of leptospirosis. World Health Organization; Obtainable from WHO Publication Centre USA. Faine, S. (1988). Leptospirosis. In A. Balows, W. J. Hausler, M. Ohashi, & A. Turano (Eds.), Laboratory diagnosis of infectious diseases: principles and practice (Vol. 1, pp. 344-352). Springer-Verlag. Faine, S. (1994). Leptospira and leptospirosis. CRC Press. Faine, S. (1999). Leptospira Species. In V. Yu, T. Merigan, & S. Barriere (Eds.), Antimicrobial Therapy and Vaccines, (Vol. 1). Williams & Wilkins. Faine, S., Adler, B., Bolin, C., & Perolat, P. (1999). Leptospire and Leptospirosis (2nd ed.). Medical Sciences, Melbourne, Australia. Fasciglione, G. F., Marini, S., D'Alessio, S., Politi, V., & Coletta, M. (2000). pH- and temperature-dependence of functional modulation in metalloproteinases. A comparison between neutrophil collagenase and gelatinases A and B. Biophysical Journal, 79(4), 2138-2149. https://doi.org/10.1016/S0006-3495(00)76461-7. Fennestad, K. L., & Borg-Petersen, C. (1962). Antibody formation in bovine foetuses infected with Leptospira saxkoebing. Acta Pathologica et Microbiologica Scandinavia Supplementum, 154, 307-308. Fletcher, W. (1928). Recent work on leptospirosis, tustsugamushi disease and tropical typhus in the Federal Malay States. Transaction of the Royal Society of Tropical Medicine and Hygiene, 21, 265-288. Fouts, D. E., Matthias, M. A., Adhikarla, H., Adler, B., Amorim-Santos, L., Berg, D. E., Bulach, D., Buschiazzo, A., Chang, Y. F., Galloway, R. L., Haake, D. A., Haft, D. H., Hartskeerl, R., Ko, A. I., Levett, P. N., Matsunaga, J., Mechaly, A. E., Monk, J. M., Nascimento, A. L., Nelson, K. E., Palsson, B., Peacock, S. J., Picardeau, M., Ricaldi, J. N., Thaipandungpanit, J., Wunder, E. A., Jr., Yang, X. F., Zhang, J. J., & Vinetz, J. M. (2016). What makes a bacterial species pathogenic?: comparative genomic analysis of the genus Leptospira. PLoS Neglected Tropical Diseases, 10(2), e0004403. https://doi.org/10.1371/journal.pntd.0004403. Galton, M. M., Menges, R. W., Shotts, E. B., Jr., Nahmias, A. J., & Heath, C. W., Jr. (1962). Leptospirosis-epidemiology, clinical manifestations in man and animals, and methods in laboratory diagnosis. Public Health Service Report, 951, 320-329. Garba, B., Bahaman, A. R., Khairani-Bejo, S., Zakaria, Z., & Mutalib, A. R. (2017). Retrospective study of leptospirosis in Malaysia. Ecohealth, 14(2), 389-398. https://doi.org/10.1007/s10393-017-1234-0 Garcia-Monco, J. C., & Benach, J. L. (2013). A disconnect between the neurospirochetoses in humans and rodent models of disease. PLoS Pathogens, 9(4), e1003288. https://doi.org/10.1371/journal.ppat.1003288. Garfin, D.E. (1990). One dimensional gel electrophoresis. Methods Enzymology, 182, 425-441. Gentilini, F., Zanoni, R. G., Zambon, E., & Turba, M. E. (2015). A comparison of two real-time polymerase chain reaction assays using hybridization probes targeting either 16S ribosomal RNA or a subsurface lipoprotein gene for detecting leptospires in canine urine. Journal of Veterinary Diagnostic Investigation, 27(6), 696-703. Glasel, J. A. (1995). Validity of nucleic acid purities monitored by 260nm/280nm absorbance ratios. Biotechniques, 18(1), 62-63. Goarant, C., Girault, D., Thibeaux, R. & Soupé-Gilbert, M-E. (2020). Isolation and culture of Leptospira from clinical and environmental samples. Methods of Molecular Biology, 2134, 1-9. Golding, C.G., Lamboo, L.L.,Beniac, D.R. & Booth, T.F. (2016). The scanning electron microscope in microbiology and diagnosis of infectious disease. Scientific Reports, Nature, 6: 265516. DOI: 10.1038/srep26516 Goldstein, S. F., & Charon, N. W. (1988). Motility of the spirochete Leptospira. Cell Motility and the Cytoskeleton, 9(2), 101-110. https://doi.org/10.1002/cm.970090202. Gomes, D. O., Ramos, G. B., Alves, V. B., Ciuffa, A. Z., Cuccato, L. P., Dos Reis, T. F., Lima, A. M., Goncalves, M. C., Tolesano, G. V., Rodrigues, V. S., & Szabo, M. P. (2017). Occurrence of anti-Leptospira spp. antibodies in Rhipidomys spp. from a forest fragment of the Brazilian Cerrado. Tropical Animal Health and Production, 49(3), 555-559. https://doi.org/10.1007/s11250-017-1227-6. Gouveia, E.L., Metcalfe, J., De Carvalho, A.L.F., Aires, T.S., Villasboas-Bisneto, J.C., Queirroz, A., Santos, A.C., Salgado, K., Reis, M.G. and Ko, A.I., 2008. Leptospirosis-associated severe pulmonary hemorrhagic syndrome, Salvador, Brazil. Emerging Infectious Diseases, 14(3), p.505. Gravekamp, C., Van de Kemp, H., Franzen, M., Carrington, D., Schoone, G. J., Van Eys, G. J., Everard, C. O., Hartskeerl, R. A., & Terpstra, W. J. (1993). Detection of seven species of pathogenic leptospires by PCR using two sets of primers. Journal of General Microbiology, 139(8), 1691-1700. https://doi.org/10.1099/00221287-139-8-1691. Grenier, D., & La, V. D. (2011). Proteases of Porphyromonas gingivalis as important virulence factors in periodontal disease and potential targets for plant-derived compounds: a review article. Current Drug Targets, 12(3), 322-331. Gross, J., Harper, E., Harris, E. D., McCroskery, P. A., Highberger, J. H., Corbett, C., & Kang, A. H. (1974). Animal collagenases: specificity of action, and structures of the substrate cleavage site. Biochemical and Biophysical Research Communications, 61(2), 605-612. Gross, J., & Nagai, Y. (1965). Specific degradation of the collagen molecule by tadpole collagenolytic enzyme. Proceedings of the National Academy of Science of the United States of America, 54(4), 1197-1204. Guerreiro, H., Croda, J., Flannery, B., Mazel, M., Matsunaga, J., Galvao Reis, M., Levett, P. N., Ko, A. I., & Haake, D. A. (2001). Leptospiral proteins recognized during the humoral immune response to leptospirosis in humans. Infection and Immunity, 69(8), 4958-4968. https://doi.org/10.1128/IAI.69.8.4958-4968.2001. Haake, D. A. (2006). Hamster model of leptospirosis. Current Protocol of Microbiology, 12(12),12. https://doi.org/10.1002/9780471729259.mc12e02s02. Haake, D. A., Chao, G., Zuerner, R. L., Barnett, J. K., Barnett, D., Mazel, M., Matsunaga, J., Levett, P. N., & Bolin, C. A. (2000). The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection. Infection and Immunity, 68(4), 2276-2285. Haake, D. A., Suchard, M. A., Kelley, M. M., Dundoo, M., Alt, D. P., & Zuerner, R. L. (2004). Molecular evolution and mosaicism of leptospiral outer membrane proteins involves horizontal DNA transfer. Journal of Bacteriology, 186(9), 2818-2828. Hagan, J. E., Moraga, P., Costa, F., Capian, N., Ribeiro, G. S., Wunder Jr, E. A., ... & Ko, A. I. (2016). Spatiotemporal determinants of urban leptospirosis transmission: four-year prospective cohort study of slum residents in Brazil. PLoS neglected tropical diseases, 10(1), e0004275. Hakim, L. (2011). Guidelines for the diagnosis, management, prevention and control of the Leptospirosis in Malaysia. Ministry of Health Malaysia, 3-14. Han, H. J., Taki, T., Kondo, H., Hirono, I., & Aoki, T. (2008). Pathogenic potential of a collagenase gene from Aeromonas veronii. Canadian Journal of Microbiology, 54(1), 1-10. https://doi.org/10.1139/w07-109. Hara-Kudo, Y., Yamakawa, Y., & Kumagai, S. (2008). Purification and some properties of Clostridium sporogenes hemorrhagic toxin. Biochemical and Biophysical Research Communications, 227, 413-418. Hartskeerl, R., Collares-Pereira, M., & Ellis, W. (2011). Emergence, control and re-emerging leptospirosis: dynamics of infection in the changing world. Clinical microbiology and infection, 17(4), 494-501 Harrington, D. J. (1996). Bacterial collagenases and collagen-degrading enzymes and their potential role in human disease. Infection and Immunity, 64(6), 1885-1891. Hathaway, S. C., & Blackmore, D. K. (1981). Ecological aspects of the epidemiology of infection with leptospires of the Ballum serogroup in the black rat (Rattus rattus) and the brown rat (Rattus norvegicus) in New Zealand. Journal of Hygiene (Lond), 87(3), 427-436. Hauk, P., Negrotto, S., Romero, E. C., Vasconcellos, S. A., Genovez, M. E., Ward, R. J., Schattner, M., Gomez, R. M., & Ho, P. L. (2005). Expression and characterization of HlyX hemolysin from Leptospira interrogans serovar Copenhageni: potentiation of hemolytic activity by LipL32. Biochemical and Biophysical Research Communications, 333(4), 1341-1347. https://doi.org/10.1016/j.bbrc.2005.06.045. Henry, R. A., Johnson, R. C., Bohlool, B. B. and Schmidt, E. L. (1971). Detection of Leptospira in soil and water by immunofluorescence staining. Applied Microbiology, 21, 953–956. Herrmann, J. L. (1993). Genomic techniques for identification of Leptospira strains. Pathologie Biologie (Paris), 41(10), 943-950. Hodges, R. T. and Ekdahl, M. O. (1973). Use of a fluorescent antibody technique for the serological differentiation of leptospiral serotypes in cultures and in bovine urine. New Zealand Veterinary Journal, 21, 109–115. Hoke, D. E., Egan, S., Cullen, P. A., & Adler, B. (2008). LipL32 is an extracellular matrix-interacting protein of Leptospira spp. and Pseudoalteromonas tunicata. Infection and Immunity, 76(5), 2063-2069. https://doi.org/10.1128/IAI.01643-07. Hovind Hougen, K. (1979). Leptopspiraceae, a new family to include Leptospira noguchi 1917 and Leptonema gen. nov. International Journal of Systematic and Evolutionary Microbiology, 29, 245-251. Hulin, M. S., & Quinn, R. (2006). Chapter 30 - Wild and Black Rats. In M. A. Suckow, S. H. Weisbroth, & C. L. Franklin (Eds.), The Laboratory Rat (Second Edition) (pp. 865-882). Academic Press. https://doi.org/https://doi.org/10.1016/B978-012074903-4/50033-9. Hyde, F. W., & Johnson, R. C. (1984). Genetic relationship of lyme disease spirochetes to Borrelia, Treponema, and Leptospira spp. Journal of Clinical Microbiology, 20(2), 151-154. Ido, Y., Hoki, R., Ito, H., & Wani, H. (1917). The rat as a carrier of Spirochaeta icterohaemorrhagiae, the causative agent of Weil's disease (spirochaetosis icterohaemorrhagica). The Journal of experimental medicine, 26(3), 341. Israel-Roming, F., Luta, G., Balan, D., Gherghina, E., Cornea, C. P., & Matei, F. (2015). Time and temperature stability of collagenase produced by Bacillus licheniformis. Agriculture and Agricultural Science Procedia, 6, 579-584. Ivanova, S., Herbreteau, V., Blasdell, K., Chaval, Y., Buchy, P., Guillard, B., & Morand, S. (2012). Leptospira and rodents in Cambodia: environmental determinants of infection. American Journal of Tropical Medicine and Hygiene, 86(6), 1032-1038. https://doi.org/10.4269/ajtmh.2012.11-0349. Jafari Dehkordi, A., Shahbazkia, H., & Ronagh, N. (2011). Evaluation of pathogenic serovars of Leptospira interrogans in dairy cattle herds of Shahrekord by PCR. Iran Journal of Microbiology, 3(3), 135-139. Joshi, Y. P., Kim, E. H., & Cheong, H. K. (2017). The influence of climatic factors on the development of hemorrhagic fever with renal syndrome and leptospirosis during the peak season in Korea: an ecologic study. BMC infectious diseases, 17(1), 1-11. Janwitthayanan, W., Keelawat, S., Payungporn, S., Lowanitchapat, A., Suwancharoen, D., Poovorawan, Y., & Chirathaworn, C. (2013). In vivo gene expression and immunoreactivity of Leptospira collagenase. Microbiological Research, 168(5), 268-272. https://doi.org/10.1016/j.micres.2012.12.005. Jittimanee, J., & Wongbutdee, J. (2014). Survey of pathogenic Leptospira in rats by polymerase chain reaction in Sisaket Province. Journal of Medical Association Thai, 97(4)20-24. Johnson, M. A., Smith, H., Joeph, P., Gilman, R. H., Bautista, C. T., Campos, K. J., Cespedes, M., Klatsky, P., Vidal, C., Terry, H., Calderon, M. M., Coral, C., Cabrera, L., Parmar, P. S., & Vinetz, J. M. (2004). Environmental exposure and leptospirosis, Peru. Emerging Infectious Diseases, 10(6), 1016-1022. https://doi.org/10.3201/eid1006.030660. Johnson, R. C. (1977). The spirochetes. Annual review of microbiology, 31(1), 89-106. Johnson, R. C., & Faine, S. (1984). Leptospira. In N. R. Krieg & J. G. Holt (Eds.), Bergey's manual of systematic bacteriology. Williams & Wilkins. Johnson, R. C., & Gary, N. D. (1962). Nutrition of "Leptospira pomona". I. Studies on a chemically defined substitute for the rabbit serum ultrafiltrate. Journal of Bacteriology, 83, 668-672. Johnson, R. C., & Gary, N. D. (1963). Nutrition of "Leptospira pomona". II. Fatty acid requirements. Journal of Bacteriology, 85, 976-982. Johnson, R. C., & Rogers, P. (1964). 5-fluorouracil as a selective agent for growth of Leptospirae. Journal of Bacteriology, 87, 422-426. Johnson, R. C., Walby, J., Henry, R. A., & Auran, N. E. (1973). Cultivation of parasitic leptospires: effect of pyruvate. Applied Microbiology, 26(1), 118-119. Jost, B. H., Adler, B., Vinh, T., & Faine, S. (1986). A monoclonal antibody reacting with a determinant on leptospiral lipopolysaccharide protects guinea pigs against leptospirosis. Journal of Medical Microbiology, 22(3), 269-275. https://doi.org/10.1099/00222615-22-3-269. Kadler, K. E., Holmes, D. F., Trotter, J. A., & Chapman, J. A. (1996). Collagen fibril formation. Biochemical Journal, 316 ( Pt 1), 1-11. Kassegne, K., Hu, W., Ojcius, D. M., Sun, D., Ge, Y., Zhao, J., Yang, X. F., Li, L., & Yan, J. (2014). Identification of collagenase as a critical virulence factor for invasiveness and transmission of pathogenic Leptospira species. Journal of Infectious Diseases, 209(7), 1105-1115. https://doi.org/10.1093/infdis/jit659. Kato, T., Takahashi, N., & Kuramitsu, H. K. (1992). Sequence analysis and characterization of the Porphyromonas gingivalis prtC gene, which expresses a novel collagenase activity. Journal of Bacteriology, 174(12), 3889-3895. Katz, A. R., Manea, S. J., & Sasaki, D. M. (1991). Leptospirosis on Kauai: investigation of a common source waterborne outbreak. American Journal of Public Health, 81(10), 1310-1312. Katz, A. R., Ansdell, V. E., Effler, P. V., Middleton, C. R., & Sasaki, D. M. (2002). Leptospirosis in Hawaii, 1974-1998: epidemiologic analysis of 353 laboratory-confirmed cases. The American journal of tropical medicine and hygiene, 66(1), 61-70. Khairani, B., Bahaman, A. R., Zamri-Saad, M., & Mutalib, A. R. (2004). The survival of Leptospira interrogans serovar hardjo in the Malaysian Environment. Journal of Animal and Veterinary Advances, 3(3), 123-129. Khaki, P. (2016). Clinical laboratory diagnosis of human leptospirosis. Int J Enteric Pathog, 4(1), 17 Khodaverdi Darian, E., Forghanifard, M. M., Moradi Bidhendi, S., Chang, Y.-F., Yahaghi, E., Esmaelizad, M., Khaleghizadeh, M., & Khaki, P. (2013). Cloning and sequence analysis of Lipl32, a surface-exposed lipoprotein of pathogenic Leptospira spp. Iranian Red Crescent Medical Journal, 15(11), e8793-e8793. https://doi.org/10.5812/ircmj.8793 Kim, S. K., Yang, J. Y., & Cha, J. (2002). Cloning and sequence analysis of a novel metalloprotease gene from Vibrio parahaemolyticus 04. Gene, 283(1-2), 277-286. King, A. M., Bartpho, T., Sermswan, R. W., Bulach, D. M., Eshghi, A., Picardeau, M., Adler, B., & Murray, G. L. (2013). Leptospiral outer membrane protein LipL41 is not essential for acute leptospirosis but requires a small chaperone protein, lep, for stable expression. Infection and Immunity, 81(8), 2768-2776. https://doi.org/10.1128/IAI.00531-13. Kitamura, H., & Hara, H. (1918). Ueber den Erreger von "Akiyami". Tokyo Medical Journal, 2056-2057. Kmety, E., & Dikken, H. (1993). Classification of the species Leptospira interrogans and history of its serovars. University Press Groningen. Ko, A. I., Galvao Reis, M., Ribeiro Dourado, C. M., Johnson, W. D., Jr., & Riley, L. W. (1999). Urban epidemic of severe leptospirosis in Brazil. Salvador Leptospirosis Study Group. Lancet, 354(9181), 820-825. Ko, A. I., Goarant, C., & Picardeau, M. (2009). Leptospira: the dawn of the molecular genetics era for an emerging zoonotic pathogen. Nature Review Microbiology, 7(10), 736-747. https://doi.org/10.1038/nrmicro2208. Krepel, C. J., Gohr, C. M., Walker, A. P., Farmer, S. G., & Edmiston, C. E. (1992). Enzymatically active Peptostreptococcus magnus: association with site of infection. Journal of Clinical Microbiology (30), 2330-2334. Kudo, Y., Vansith, K., Rin, E., Uchida, K., Kodama, S., Fukui, T., Masuda, S., & Masuzawa, T. (2018). Molecular epidemiological survey of Leptospira infection of wild rodents in the urban settlement of Cambodia. Vector Borne Zoonotic Diseases, 18(3), 144-150. https://doi.org/10.1089/vbz.2017.2198. Kuhn, K. (1995). Basement membrane (type IV) collagen. Matrix Biology, 14(6), 439-445. Kuriakose, M., Eapen, C. K., & Paul, R. (1997). Leptospirosis in Kolenchery, Kerala, India: epidemiology, prevalent local serogroups and serovars and a new serovar. European Journal of Epidemiology, 13(6), 691-697. Lacerda, H.G., Monteiro, G.R., Oliveira, C.C., Suassuna, F.B., Queiroz, J.W., Barbosa, J.D., Martins, D.R., Reis, M.G., Ko, A.I. and Jeronimo, S.M. (2008). Leptospirosis in a subsistence farming community in Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene, 102(12), 1233-1238. Lane, G. K., & Faine, S. (1963). Urinary antibody during renal damage due to leptospiral infection in mice. Journal of Infectious Diseases, 113, 110-112. Lagadec, E., Gomard, Y., Le Minter, G., Cordonin, C., Cardinale, E., Ramasindrazana, B., Dietrich, M., Goodman, S. M., Tortosa, P., & Dellagi, K. (2016). Identification of Tenrec ecaudatus, a wild mammal introduced to Mayotte island, as a reservoir of the newly identified human pathogenic Leptospira mayottensis. PLoS Neglected Tropical Diseases, 10(8), e0004933. https://doi.org/10.1371/journal.pntd.0004933 Latifah, I., Rahmat, M. S., Hayarti, K. B., Paramasvaran, S., Azizah, M. R., Imran, F., & Normaznah, Y. (2012). Prevalence of leptospiral DNA among wild rodents from a selected area in Beguk Dam Labis, Segamat, Johor, Malaysia. Malaysian Journal of Pathology , 34(2), 157-159. Lee, J. H., Kim, G. T., Lee, J. Y., Jun, H. K., Yu, J. H., & Kong, I. S. (1998). Isolation and sequence analysis of metalloprotease gene from Vibrio mimicus. Biochima et Biophysica Acta, 1384(1), 1-6. Lee, L. T. (2017). Declare all-out war on rats. The Star Online. Retrieved 21 June from http://www.thestar.com.my/opinion/letters/2017/02/18/declare-allout-war-on-rats/ Lee, S. H., Kim, K. A., Park, Y. G., Seong, I. W., Kim, M. J., & Lee, Y. J. (2000). Identification and partial characterization of a novel hemolysin from Leptospira interrogans serovar lai. Gene, 254(1-2), 19-28. Lee, S. H., Kim, S., Park, S. C., & Kim, M. J. (2002). Cytotoxic activities of Leptospira interrogans hemolysin SphH as a pore-forming protein on mammalian cells. Infection and Immunity, 70(1), 315-322. Leon, A., Pronost, S., Tapprest, J., Foucher, N., Blanchard, B., Andre-Fontaine, G., Laugier, C., Fortier, G., & Leclercq, R. (2006). Identification of pathogenic Leptospira strains in tissues of a premature foal by use of polymerase chain reaction analysis. Malaysian Journal of Pathology, 18(2), 218-221. https://doi.org/10.1177/104063870601800216. Levett, P. N., & Whittington, C. U. (1998). Evaluation of the indirect hemagglutination assay for diagnosis of acute leptospirosis. Journal of Clinical Microbiology, 36(1), 11-14. Levett, P. N. (2001). Leptospirosis. Clinical Microbiology Reviews, 14(2), 296-326. https://doi.org/10.1128/CMR.14.2.296-326.2001. Levett, P. N., Morey, R. E., Galloway, R., Steigerwalt, A. G., & Ellis, W. A. (2005). Reclassification of Leptospira parva Hovind-Hougen et al. 1982 as Turneriella parva gen. nov., comb. nov. International Journal of Systematic and Evolutionary Microbiology, 55 (Pt 4), 1497-1499. https://doi.org/10.1099/ijs.0.63088-0. Leys, S. P., & Riesgo, A. (2012). Epithelia, an evolutionary novelty of metazoans. Journal of Experimental Zoology Part B. Molecular and Developmental Evolution, 318(6), 438-447. https://doi.org/10.1002/jez.b.21442. Li, D. K., Bao, L., Zhang, Y., & Sun, Z. (2010b). Construction and expression of recombinant Mycobacterium bovis BCG with the ompA-like membrane protein gene Loa22 of Leptospira interrogans serovar. Sichuan Da Xue Xue Bao Yi Xue Ban, 41(2), 189-193. Li, S., Ojcius, D. M., Liao, S., Li, L., Xue, F., Dong, H., & Yan, J. (2010a). Replication or death: distinct fates of pathogenic Leptospira strain Lai within macrophages of human or mouse origin. Innate Immunity, 16(2), 80-92. https://doi.org/10.1177/1753425909105580. Li, S., Wang, D., Zhang, C., Wei, X., Tian, K., Li, X., Nie, Y., Liu, Y., Yao, G., Zhou, J., Tang, G., Jiang, X., & Yan, J. (2013). Source tracking of human leptospirosis: serotyping and genotyping of Leptospira isolated from rodents in the epidemic area of Guizhou province, China. BMC Microbiology, 13, 75. https://doi.org/10.1186/1471-2180-13-75. Lim, V. K. (2011). Leptospirosis: a re-emerging infection. Malaysian Journal of Pathology, 33(1), 1-5. Lingappa, J., Kuffner, T., Tappero, J., Whitworth, W., Mize, A., Kaiser, R., & McNicholl, J. (2004). HLA-DQ6 and ingestion of contaminated water: possible gene-environment interaction in an outbreak of Leptospirosis. Genes and Immunity, 5(3), 197-202. https://doi.org/10.1038/sj.gene.6364058. Litvin, V., & Golubev, M. V. (1982). Analysis of the forrmation and dynamics of the "outside the body" portion of a population of the causative agent in a natural focus of leptospirosis. Žurnal mikrobiologii, ėpidemiologii immunobiologii (3), 32-35. Liverpool, J., Francis, S., Liverpool, C. E., Dean, G. T., & Mendez, D. D. (2008). Leptospirosis: case reports of an outbreak in Guyana. Annals of Tropical Medicine & Parasitology, 102(3), 239-245. Loan, H. K., Van Cuong, N., Takhampunya, R., Kiet, B. T., Campbell, J., Them, L. N., Bryant, J. E., Tippayachai, B., Van Hoang, N., Morand, S., Hien, V. B., & Carrique-Mas, J. J. (2015). How important are rats as vectors of leptospirosis in the Mekong Delta of Vietnam? Vector Borne Zoonotic Discovery, 15(1), 56-64. https://doi.org/10.1089/vbz.2014.1613. Lodish, H., Berk, A., Zipursky, S., Matsudaira, P., Baltimore, D., & Darnell, J. (2000). Molecular Cell Biology 4th edition. W. H. Freeman. McBride, A. J., Athanazio, D. A., Reis, M. G., & Ko, A. I. (2005). Leptospirosis. Current opinion in infectious diseases, 18(5), 376-386 Maclennan, J. D., Mandl, I., & Howes, E. L. (1953). Bacterial digestion of collagen. Journal of Clinical Invesigation, 32(12), 1317-1322. https://doi.org/10.1172/JCI102860. Maeda, H., & Yamamoto, T. (1996). Pathogenic mechanisms induced by microbial proteases in microbial infections. Biological Chemistry Hoppe-Seyler, 377(4), 217-226. Makinen, K. K., & Makinen, P. L. (1987). Purification and properties of an extracellular collagenolytic protease produced by the human oral bacterium Bacillus cereus (strain Soc 67). Journal of Biological Chemistry, 262(26), 12488-12495. Martinez-Lopez, D. G., Fahey, M., & Coburn, J. (2010). Responses of human endothelial cells to pathogenic and non-pathogenic Leptospira species. PLoS Neglected Tropical Diseases, 4(12), e918. https://doi.org/10.1371/journal.pntd.0000918. Maschmann, E. (1937). Uber Bakterienproteasen II. Biochemische Zeitschrift, 295, 1-10. Matsushita, O., Jung, C. M., Katayama, S., Minami, J., Takahashi, Y., & Okabe, A. (1999). Gene duplication and multiplicity of collagenases in Clostridium histolyticum. Journal of Bacteriology, 181(3), 923-933. Matsushita, O., Jung, C. M., Minami, J., Katayama, S., Nishi, N., & Okabe, A. (1998). A study of the collagen-binding domain of a 116-kDa Clostridium histolyticum collagenase. Journal of Biological Chemistry, 273(6), 3643-3648. Matsushita, O., Koide, T., Kobayashi, R., Nagata, K., & Okabe, A. (2001). Substrate recognition by the collagen-binding domain of Clostridium histolyticum class I collagenase. Journal of Biological Chemistry, 276(12), 8761-8770. https://doi.org/10.1074/jbc.M003450200. Matsushita, O., Yoshihara, K., Katayama, S., Minami, J., & Okabe, A. (1994a). Purification and characterization of Clostridium perfringens 120-kilodalton collagenase and nucleotide sequence of the corresponding gene. Journal of Bacteriology, 176(1), 149-156. Matsushita, O., Yoshihara, K., Katayama, S., Minami, J., & Okabe, A. (1994b). Purification and characterization of Clostridium perfringens 120-kilodalton collagenase and nucleotide sequence of the corresponding gene. Journal of Bacteriology, 176(1), 149. https://doi.org/10.1128/jb.176.1.149-156.1994. Matthias, M. A., & Levett, P. N. (2002). Leptospiral carriage by mice and mongooses on the island of Barbados. West Indian Medical Journal, 51(1), 10-13. Mayer-Scholl, A., Teifke, J. P., Huber, N., Luge, E., Bier, N. S., Nockler, K., & Ulrich, R. G. (2019). Leptospira spp. inrodents and shrews from Afghanistan. Journal of Wildlife Diseases, 55(2), 477-481. https://doi.org/10.7589/2018-05-122. Meerburg, B. G., Singleton, G. R., & Kijlstra, A. (2009). Rodent-borne diseases and their risks for public health. Critical Reviews in Microbiology, 35, 221-270. Merien, F., Amouriaux, P., Perolat, P., Baranton, G., & Saint Girons, I. (1992). Polymerase chain reaction for detection of Leptospira spp. in clinical samples. Journal of Clinical Microbiology, 30(9), 2219-2224. Merien, F., Baranton, G., & Perolat, P. (1995). Comparison of polymerase chain reaction with microagglutination test and culture for diagnosis of leptospirosis. Journal of Infectious Diseases, 172(1), 281-285. Miller, E. J., & Gay, S. (1987). The collagens: an overview and update. Methods Enzymology, 144, 3-41. MOH (2011). Guidelines for the diagnosis, management, prevention and control of leptospirosis in Malaysia. Disease Control Division, Department of Public Health, Ministry of Health Malaysia. Mohamad Ikbal, N., Bhassu, S., Simarani, K., Uni, S., Chan, C., & Omar, H. (2019). Prevalence and genetic divergence of Leptospira interrogans and Leptospira borgpetersenii in house rats (Rattus rattus) from Peninsular Malaysia. Asian Pacific Journal of Tropical Medicine, 12(10), 463-471. https://doi.org/10.4103/1995-7645.269906. Mohamad Safiee, A. W., Mohd Ali, M. R., Fauzi, M. H., Muhd Besari, A., Yean Yean, C., Neela, V. K., & Ismail, N. (2020). Leptospiral Culture without 5’-Fluorouracil Revealed Improved Leptospira Isolation from Febrile Patients in North-Eastern Malaysia. International journal of environmental research and public health, 17(4), 1307. Mohamed-Hassan, S. N., Bahaman, A. R., Mutalib, A. R., & Khairani-Bejo, S. (2010). Serological prevalence of leptospiral infection in wild rats at the National Service Training Centres in Kelantan and Terengganu. Tropical Biomedicine, 27(1), 30-32. Mohd Ali, M. R., Mohamad Safiee, A. W., Yusof, N. Y., Fauzi, M. H., Yean Yean, C., & Ismail, N. (2018). Isolation of Leptospira kmetyi from residential areas of patients with leptospirosis in Kelantan, Malaysia. Journal of Infection Public Health, 11(4), 578-580. https://doi.org/10.1016/j.jiph.2017.12.008. Mookhtiar, K. A., & Van Wart, H. E. (1992). Clostridium histolyticum collagenases: a new look at some old enzymes. Matrix Supplement, 1, 116-126. Morey, R. E., Galloway, R. L., Bragg, S. L., Steigerwalt, A. G., Mayer, L. W., & Levett, P. N. (2006). Species-specific identification of Leptospiraceae by 16S rRNA gene sequencing. Journal of clinical microbiology, 44(10), 3510-3516. Morton, H. E. (1942). Susceptibility of syrian hamsters to leptospirosis. Proceedings of the Society for Experimental Biology and Medicine, 49(4), 566-568. https://doi.org/10.3181/00379727-49-13630. Murgia, R., Riquelme, N., Baranton, G., & Cinco, M. (1997). Oligonucleotides specific for pathogenic and saprophytic Leptospira occurring in water. FEMS Microbiology Letters, 148(1), 27-34. Murray, G. L. (2015). The molecular basis of leptospiral pathogenesis. Leptospira and Leptospirosis, 139-185. Murray, G. L., Srikram, A., Henry, R., Hartskeerl, R. A., Sermswan, R. W., & Adler, B. (2010). Mutations affecting Leptospira interrogans lipopolysaccharide attenuate virulence. Molecular Microbiology, 78(3), 701-709. https://doi.org/10.1111/j.1365-2958.2010.07360. Murray, G. L., Srikram, A., Hoke, D. E., Wunder, E. A., Jr., Henry, R., Lo, M., Zhang, K., Sermswan, R. W., Ko, A. I., & Adler, B. (2009). Major surface protein LipL32 is not required for either acute or chronic infection with Leptospira interrogans. Infection and Immunity, 77(3), 952-958. https://doi.org/10.1128/IAI.01370-08. Myers, D. M. (1976). Serological studies and isolations of serotype hardjo and Leptospira biflexa strains from horses of Argentina. Journal of Clinical Microbiology, 3(6), 548-555. Nahori, M. A., Fournie-Amazouz, E., Que-Gewirth, N. S., Balloy, V., Chignard, M., Raetz, C. R., Saint Girons, I., & Werts, C. (2005). Differential TLR recognition of leptospiral lipid A and lipopolysaccharide in murine and human cells. Journal of Immunology, 175(9), 6022-6031. Nally, J. E., Chow, E., Fishbein, M. C., Blanco, D. R., & Lovett, M. A. (2005). Changes in lipopolysaccharide O antigen distinguish acute versus chronic Leptospira interrogans infections. Infection and Immunity, 73(6), 3251-3260. https://doi.org/10.1128/IAI.73.6.3251-3260.2005. Nguyen, T. X., Alegre, E. R., & Kelley, S. T. (2006). Phylogenetic analysis of general bacterial porins: a phylogenomic case study. Journal of Molecular Microbiology and Biotechnology, 11(6), 291-301. Noguchi, H. (1918a). A comparative study of experimental prophylactic inoculation against Leptospira icterohaemorrhagiae. Journal of Experimental Medicine, 28(5), 561-570. Noguchi, H. (1918b). Morphological characteristics and nomenclature of Leptospira (Spirochaeta) Icterohaemorrhagiae (Inada and Ido). Journal of Experimental Medicine, 27(5), 575-592. Oie, S., Koshiro, A., Konishi, H., & Yoshii, Z. (1986). In vitro evaluation of combined usage of fosfomycin and 5-fluorouracil for selective isolation of Leptospira species. Journal of Clinical Microbiology, 23(6), 1084-1087. Oyama, V. I., Steinman, H. G., & Eagle, H. (1953). The nutritional requirements of treponemata. V. A detoxified lipide as the essential growth factor supplied by crystalline serum albumin. Journal of Bacteriology, 65, 609-616. Packchanian, A. (1940). Susceptibility and resistance of certain species of American deer mice, genus Peromyscus, and other rodents to Leptospira icterohaemorrhagiae. Public Health Report, 55, 1389-1402. Palaniappan, R. U., Ramanujam, S., & Chang, Y. F. (2007). Leptospirosis: pathogenesis, immunity, and diagnosis. Current Opinion in Infectious Diseases, 20(3), 284-292. https://doi.org/10.1097/QCO.0b013e32814a5729. Pappas, G., Papadimitriou, P., Siozopoulou, V., Christou, L., & Akritidis, N. (2008). The globalization of leptospirosis: worldwide incidence trends. International journal of infectious diseases, 12(4), 351-357. Pereira, M. M., & Andrade, J. (1988). Epidemiological aspects of leptospirosis in a slum area in the city of Rio de Janeiro, Brazil. Search for leptospires and specific antibodies in rodents. Transactions of the Royal Society of Tropical Medicine and Hygiene, 82(5), 768-770. Perez, J., Brescia, F., Becam, J., Mauron, C., & Goarant, C. (2011). Rodent abundance dynamics and leptospirosis carriage in an area of hyper-endemicity in New Caledonia. PLoS neglected tropical diseases, 5(10), e1361. Perolat, P., Chappel, R. J., Adler, B., Baranton, G., Bulach, D. M., Billinghurst, M. L., Letocart, M., Merien, F., & Serrano, M. S. (1998). Leptospira fainei sp. nov., isolated from pigs in Australia. International Journal of Systematic and Evolutionary Microbiology, 48 Pt 3, 851-858. https://doi.org/10.1099/00207713-48-3-851. Picardeau, M. (2017). Virulence of the zoonotic agent of leptospirosis: still terra incognita? Nature Review Microbiology, 15(5), 297-307. https://doi.org/10.1038/nrmicro.2017.5. Pinne, M., & Haake, D. A. (2009). A comprehensive approach to identification of surface-exposed, outer membrane-spanning proteins of Leptospira interrogans. PLoS One, 4(6), e6071. https://doi.org/10.1371/journal.pone.0006071. Pinne, M., & Haake, D. A. (2013). LipL32 is a subsurface lipoprotein of Leptospira interrogans: presentation of new data and reevaluation of previous studies. PLoS One, 8(1), e51025. https://doi.org/10.1371/journal.pone.0051025. Poilane, I., Karjalainen, T., Barc, M. C., Bourlioux, P., & Collignon, A. (1998). Protease activity of Clostridium difficile strains. Canadian Journal of Microbiology, 44(2), 157-161. Popoff, M. R., & Bouvet, P. (2009). Clostridial toxins. Future Microbiology, 4(8), 1021-1064. https://doi.org/10.2217/fmb.09.72. Pruteanu, M., Hyland, N. P., Clarke, D. J., Kiely, B., & Shanahan, F. (2011). Degradation of the extracellular matrix components by bacterial-derived metalloproteases: implications for inflammatory bowel diseases. Inflammatory Bowel Diseases, 17(5), 1189-1200. https://doi.org/10.1002/ibd.21475. Pui, C. F., Bilung, L. M., Apun, K., & Su'ut, L. (2017). Diversity of Leptospira spp. in rats and environment from urban areas of Sarawak, Malaysia. Journal of Tropical Medicine, 2017, 3760674. https://doi.org/10.1155/2017/3760674. Radi, M.F.M., Hashim, J.H., Jaafar, M.H., Hod, R., Ahmad, N., Nawi, A.M., Baloch, G.M., Ismail, R. and Ayub, N.I.F., 2018. Leptospirosis outbreak after the 2014 major flooding event in Kelantan, Malaysia: a spatial-temporal analysis. The American Journal of Tropical Medicine and Hygiene, 98(5), p.1281. Radostitis, O. M., Blood, D. C., & Gay, C. C. (1994). Veterinary medicine. A textbook of the diseases of cattle, sheep, pigs, goat and horses. Ed 8th. Rafizah, A. A., Aziah, B. D., Azwany, Y. N., Imran, M. K., Rusli, A. M., Nazri, S. M., Nikman, A. M., Nabilah, I., Asma, H. S., Zahiruddin, W. M., & Zaliha, I. (2013). Risk factors of leptospirosis among febrile hospital admissions in northeastern Malaysia. Preventive Medicine, 57 S11-13. https://doi.org/10.1016/j.ypmed.2012.12.017. Ramadass, P., Jarvis, B. D., Corner, R. J., Penny, D., & Marshall, R. B. (1992). Genetic characterization of pathogenic Leptospira species by DNA hybridization. International Journal of Systematic and Evolutionary Microbiology, 42(2), 215-219. https://doi.org/10.1099/00207713-42-2-215. Rawlings, N. D., & Barrett, A. J. (1995). Families of aspartic peptidases, and those of unknown catalytic mechanism. Methods Enzymology, 248, 105-120. Reis, R. B., Ribeiro, G. S., Felzemburgh, R. D., Santana, F. S., Mohr, S., Melendez, A. X., ... & Ko, A. I. (2008). Impact of environment and social gradient on Leptospira infection in urban slums. PLoS Neglected Tropical Diseases, 2(4), e228. Ren, S. X., Fu, G., Jiang, X. G., Zeng, R., Miao, Y. G., Xu, H., Zhang, Y. X., Xiong, H., Lu, G., Lu, L. F., Jiang, H. Q., Jia, J., Tu, Y. F., Jiang, J. X., Gu, W. Y., Zhang, Y. Q., Cai, Z., Sheng, H. H., Yin, H. F., Zhang, Y., Zhu, G. F., Wan, M., Huang, H. L., Qian, Z., Wang, S. Y., Ma, W., Yao, Z. J., Shen, Y., Qiang, B. Q., Xia, Q. C., Guo, X. K., Danchin, A., Saint Girons, I., Somerville, R. L., Wen, Y. M., Shi, M. H., Chen, Z., Xu, J. G., & Zhao, G. P. (2003). Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing. Nature, 422(6934), 888-893. https://doi.org/10.1038/nature01597. Renesto, P., Lorvellec-Guillon, K., Drancourt, M., & Raoult, D. (2000). rpoB gene analysis as a novel strategy for identification of spirochetes from the genera Borrelia, Treponema, and Leptospira. Journal of clinical microbiology, 38(6), 2200-2203. Ribeiro, M. A., Assis, C. S. N., & Romero, E. C. (1994). Serodiagnosis of human leptospirosis employing immunodominant antigen. Serodiagnosis and immunotherapy in infectious disease, 6(3), 140-144. Richards, D. R., & Friess, D. A. (2016). Rates and drivers of mangrove deforestation in Southeast Asia, 2000–2012. Proceedings of the National Academy of Sciences, 113(2), 344. https://doi.org/10.1073/pnas.1510272113. Ridzlan, F. R., Bahaman, A. R., Khairani-Bejo, S., & Mutalib, A. R. (2010). Detection of pathogenic Leptospira from selected environment in Kelantan and Terengganu, Malaysia. Tropical Biomedicine, 27(3), 632-638. Ridzuan, J. M., Aziah, B. D., & Zahiruddin, W. M. (2016). Study on Seroprevalence and Leptospiral Antibody Distribution among High-risk Planters in Malaysia. Osong Public Health and Research Perspectives, 7(3), 168-171. https://doi.org/10.1016/j.phrp.2016.04.006. Ringen, L. M. (1960). The detection of leptospiral antigen in bovine urine by means of a hemolytic reaction (UHL). Journal of Immunology, 84, 582-585. Ris, D. R., & Hamel, K. L. (1978). The detection of Leptospirae in cattle urine. New Zealand Veterinary Journal, 26(10), 246, 255-246. https://doi.org/10.1080/00480169.1978.34556. Robbins, G. T., Hahn, B. L., Evangelista, K. V., Padmore, L., Aranda, P. S., & Coburn, J. (2015). Evaluation of cell binding activities of Leptospira ECM adhesins. PLoS Neglected Tropical Diseases, 9(4), e0003712. https://doi.org/10.1371/journal.pntd.0003712. Robertson, C., Nelson, T. A., & Stephen, C. (2012). Spatial epidemiology of suspected clinical leptospirosis in Sri Lanka. Epidemiology & Infection, 140(4), 731-743. Samrot, A.V., Sean, T.C., Bhavya, K.S., Sahithya, C.S., Chan-Drasekaran, S., Palanisamy, R., Robinson, E.R., Subbiah, S.K. and Mok, P.L. (2021). Leptospiral infection, pathogenesis and its diagnosis—A review. Pathogens, 10(2), 145. Sansonetti, P. J. (1993). Bacterial pathogens, from adherence to invasion: comparative strategies. Medical Microbiology and Immunity, 182(5), 223-232. Schneider, M.C., Nájera, P., Aldighieri, S., Bacallao, J., Soto, A., Marquiño, W., Altamirano, L., Saenz, C., Marin, J., Jimenez, E. and Moynihan, M. (2012). Leptospirosis outbreaks in Nicaragua: identifying critical areas and exploring drivers for evidence-based planning. International journal of environmental research and public health, 9(11), pp.3883-3910. Seddon, S. V., Hemingway, I., & Borriello, S. P. (1990). Hydrolytic enzyme production by Clostridium difficile and its relationship to toxin production and virulence in the hamster model. Journal of Medical Microbiology, 31(3), 169-174. https://doi.org/10.1099/00222615-31-3-169. Sejvar, J., Bancroft, E., Winthrop, K., Bettinger, J., Bajani, M., Bragg, S., Shutt, K., Kaiser, R., Marano, N., Popovic, T., Tappero, J., Ashford, D., Mascola, L., Vugia, D., Perkins, B., Rosenstein, N., & Eco-Challenge Investigation, T. (2003). Leptospirosis in "Eco-Challenge" athletes, Malaysian Borneo, 2000. Emerging Infectious Diseases, 9(6), 702-707. https://doi.org/10.3201/eid0906.020751. Sekhar, W. Y., Soo, E. H., Gopalakrishnan, V., & Devi, S. (2000). Leptospirosis in Kuala Lumpur and the comparative evaluation of two rapid commercial diagnostic kits against the MAT test for the detection of antibodies to leptospira interrogans. Singapore Medical Journal, 41(8), 370-375. Sethi, S., Sharma, N., Kakkar, N., Taneja, J., Chatterjee, S. S., Banga, S. S., & Sharma, M. (2010). Increasing trends of leptospirosis in northern India: a clinico-epidemiological study. PLoS neglected tropical diseases, 4(1), e579. Shang, E. S., Summers, T. A., & Haake, D. (1996). Molecular cloning and sequence analysis of the gene encoding LipL41, a surface-exposed lipoprotein of pathogenic Leptospira species. Infection and Immunity, 64, 2322-2330. Shimizu, T., Matsusaka, E., Nagakura, N., Takayanagi, K., Masuzawa, T., Iwamoto, Y., Morita, T., Mifuchi, I., & Yanagihara, Y. (1987). Chemical properties of lipopolysaccharide-like substance (LLS) extracted from Leptospira interrogans serovar canicola strain Moulton. Microbiology and Immunology. 31, 717-726. Sibon, P. (2011, 3 August 2011). No mystery in deaths. The Borneo Post. Retrieved 30 November from http://www.theborneopost.com/2011/08/03/no-mystery-in-deaths. Slack, A. T., Kalambaheti, T., Symonds, M. L., Dohnt, M. F., Galloway, R. L., Steigerwalt, A. G., Chaicumpa, W., Bunyaraksyotin, G., Craig, S., Harrower, B. J., & Smythe, L. D. (2008). Leptospira wolffii sp. nov., isolated from a human with suspected leptospirosis in Thailand. International Journal of Systematic and Evolutionary Microbiology, 58(Pt 10), 2305-2308. https://doi.org/10.1099/ijs.0.64947-0. Slack, A. T., Khairani-Bejo, S., Symonds, M. L., Dohnt, M. F., Galloway, R. L., Steigerwalt, A. G., Bahaman, A. R., Craig, S., Harrower, B. J., & Smythe, L. D. (2009). Leptospira kmetyi sp. nov., isolated from an environmental source in Malaysia. International Journal of Systematic and Evolutionary Microbiology, 59(Pt 4), 705-708. https://doi.org/10.1099/ijs.0.002766-0. Sman, C. (2016). Sarawak has second highest number of leptospirosis cases. BorneoPost. Retrieved 21 June from http://www.theborneopost.com/2016/09/30/sarawak-has-second-highest-number-of-leptospirosis-cases. Smith, C. E., Turner, L. H., Harrison, J. L., & Broom, J. C. (1961a). Animal leptospirosis in Malaya: 1. Methods, zoogeographical background, and broad analysis of results. Bulletin World Health Organization, 24(1), 5-21. Smith, C. E., Turner, L. H., Harrison, J. L., & Broom, J. C. (1961b). Animal leptospirosis in Malaya: 2. Localities sampled. Bulletin World Health Organization, 24(1), 23-34. Smith, C. R., Ketterer, P. J., McGowan, M. R., & Corney, B. G. (1994). A review of laboratory techniques and their use in the diagnosis of Leptospira interrogans serovar hardjo infection in cattle. Australian Veterinary Journal, 71(9), 290-294. Soares, G. C., da Silva, B. A., Dos Santos, M. H., da Costa, A. F., Dos Santos, A. L., Morandi, V., & Nagao, P. E. (2008). Metallopeptidases produced by group B Streptococcus: influence of proteolytic inhibitors on growth and on interaction with human cell lineages. International Journal of Molecular Medicine, 22(1), 119-125. Srinivasan, R., Karaoz, U., Volegova, M., MacKichan, J., Kato-Maeda, M., Miller, S., Nadarajan, R., Brodie, E. L., & Lynch, S. V. (2015). Use of 16S rrna gene for identification of a broad range of clinically relevant bacterial pathogens. PLoS One, 10(2), e0117617. Stack, M. S., & Gray, R. D. (1989). Comparison of vertebrate collagenase and gelatinase using a new fluorogenic substrate peptide. Journal of Biological Chemistry, 264(8), 4277-4281. Stackebrandt, E., Chertkov, O., Lapidus, A., Nolan, M., Lucas, S., Hammon, N., Deshpande, S., Cheng, J.-F., Tapia, R., Goodwin, L. A., Pitluck, S., Liolios, K., Pagani, I., Ivanova, N., Mavromatis, K., Mikhailova, N., Huntemann, M., Pati, A., Chen, A., Palaniappan, K., Land, M., Pan, C., Rohde, M., Gronow, S., Göker, M., Detter, J. C., Bristow, J., Eisen, J. A., Markowitz, V., Hugenholtz, P., Woyke, T., Kyrpides, N. C., & Klenk, H.-P. (2013). Genome sequence of the free-living aerobic spirochete Turneriella parva type strain (HT), and emendation of the species Turneriella parva. Standards in Genomic Sciences, 8(2), 228-238. https://doi.org/10.4056/sigs.3617113. Stern, E. J., Galloway, R., Shadomy, S. V., Wannemuehler, K., Atrubin, D., Blackmore, C., Wofford, T., Wilkins, P. P., Ari, M. D., Harris, L., & Clark, T. A. (2010). Outbreak of leptospirosis among adventure race participants in Florida, 2005. Clinical Infectious Diseases, 50(6), 843-849. https://doi.org/10.1086/650578. St

Similar Items