{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:31:05Z","timestamp":1790469065593,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health, Malaysia","award":["KKM510-4\/4\/3\/3Jld.4(85)"],"award-info":[{"award-number":["KKM510-4\/4\/3\/3Jld.4(85)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The ability of Leptospirae to persist in environments and animal hosts but to cause clinically highly variable disease in humans has made leptospirosis the most common zoonotic disease. Considering the paucity of data on variation in complete genomes of human pathogenic Leptospirae, we have used a combination of Single Molecule Real-Time (SMRT) and Illumina sequencing to obtain complete genome sequences of six human clinical L. interrogans isolates from Malaysia. All six contained the larger (4.28\u20134.56 Mb) and smaller (0.34\u20130.395 Mb) chromosome typical of human pathogenic Leptospirae and 0\u20137 plasmids. Only 24% of the plasmid sequences could be matched to databases. We identified a chromosomal core genome of 3318 coding sequences and strain-specific accessory genomes of 49\u2013179 coding sequences. These sequences enabled detailed genomic strain typing (Genome BLAST Distance Phylogeny, DNA\u2013DNA hybridization, and multi locus sequence typing) and phylogenetic classification (whole-genome SNP genotyping). Even though there was some shared synteny and collinearity across the six genomes, there was evidence of major genome rearrangement, likely driven by horizontal gene transfer and homologous recombination. Mobile genetic elements were identified in all strains in highly varying numbers, including in the rfb locus, which defines serogroups and contributes to immune escape and pathogenesis. On the other hand, there was high conservation of virulence-associated genes including those relating to sialic acid, alginate, and lipid A biosynthesis. These findings suggest (i) that the antigenic variation, adaption to various host environments, and broad spectrum of virulence of L. interrogans are in part due to a high degree of genomic plasticity and (ii) that human pathogenic strains maintain a core set of genes required for virulence.<\/jats:p>","DOI":"10.3390\/pathogens10091198","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T21:47:11Z","timestamp":1631742431000},"page":"1198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Complete Genome Sequencing of Leptospira interrogans Isolates from Malaysia Reveals Massive Genome Rearrangement but High Conservation of Virulence-Associated Genes"],"prefix":"10.3390","volume":"10","author":[{"given":"Siti Roszilawati","family":"Ramli","sequence":"first","affiliation":[{"name":"Research Group Biomarkers for Infectious Diseases, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"},{"name":"Department of Biotechnology, Technical University Braunschweig, 38106 Braunschweig, Germany"},{"name":"Bacteriology Unit, Institute for Medical Research, National Institute of Health, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8420-8161","authenticated-orcid":false,"given":"Boyke","family":"Bunk","sequence":"additional","affiliation":[{"name":"Leibniz Institute German Collection of Microorganisms and Cell Cultures (DSMZ), 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathrin","family":"Spr\u00f6er","sequence":"additional","affiliation":[{"name":"Leibniz Institute German Collection of Microorganisms and Cell Cultures (DSMZ), 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Geffers","sequence":"additional","affiliation":[{"name":"Genome Analytics, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Jarek","sequence":"additional","affiliation":[{"name":"Genome Analytics, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabin","family":"Bhuju","sequence":"additional","affiliation":[{"name":"Genome Analytics, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marga","family":"Goris","sequence":"additional","affiliation":[{"name":"Leptospirosis Reference Centre, Amsterdam Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahlawati","family":"Mustakim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Tuanku Ampuan Rahimah, Klang 41672, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3434-2311","authenticated-orcid":false,"given":"Frank","family":"Pessler","sequence":"additional","affiliation":[{"name":"Research Group Biomarkers for Infectious Diseases, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"},{"name":"Centre for Individualised Infection Medicine, 30625 Hannover, Germany"},{"name":"Research Group Biomarkers for Infectious Diseases, TWINCORE Center for Experimental and Clinical Infection Research, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mwachui, M.A., Crump, L., Hartskeerl, R., Zinsstag, J., and Hattendorf, J. 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