Complete Genome Sequencing of Leptospira interrogans Isolates from Malaysia Reveals Massive Genome Rearrangement but High Conservation of Virulence-Associated Genes. Pathogens, 10 (1198). pp. 1-18. (2021)
Abstract
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 (4.28–4.56 Mb) and smaller (0.34–0.395 Mb) chromosome typical of human
pathogenic Leptospirae and 0–7 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 49–179 coding sequences. These sequences enabled detailed genomic strain
typing (Genome BLAST Distance Phylogeny, DNA–DNA 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.
| Item Type: | Article |
|---|---|
| Keywords: | Biomarker, Classification, Genetics, Genome, Genome rearrangement, Leptospira, Leptospira interrogans, Leptospirosis, Rfb locus, Whole genome, Virulence |
| Taxonomy: | By Niche > Genome > Animal Genome Mapping By Niche > Genome > Genomes |
| Local Content Hub: | Niche > Food Technology |
| Depositing User: | Rizana Mohd Radwan |
| Date Deposited: | 23 Aug 2024 08:19 |
| Last Modified: | 23 Aug 2024 08:19 |
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