Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing
Shuang-Xi Ren1, Gang Fu, Xiu-Gao Jiang
1Chinese National Human Genome Center at Shanghai, 250 Bi Bo Road, Zhang Jiang High Tech Park, Shanghai 201203, China.
Abstract:
Leptospirosis is a widely spread disease of global concern. Infection causes flu-like episodes with frequent severe renal and hepatic damage, such as haemorrhage and jaundice. In more severe cases, massive pulmonary haemorrhages, including fatal sudden haemoptysis, can occur. Here we report the complete genomic sequence of a representative virulent serovar type strain (Lai) of Leptospira interrogans serogroup Icterohaemorrhagiae consisting of a 4.33-megabase large chromosome and a 359-kilobase small chromosome, with a total of 4,768 predicted genes. In terms of the genetic determinants of physiological characteristics, the facultatively parasitic L. interrogans differs extensively from two other strictly parasitic pathogenic spirochaetes, Treponema pallidum and Borrelia burgdorferi, although similarities exist in the genes that govern their unique morphological features. A comprehensive analysis of the L. interrogans genes for chemotaxis/motility and lipopolysaccharide synthesis provides a basis for in-depth studies of virulence and pathogenesis. The discovery of a series of genes possibly related to adhesion, invasion and the haematological changes that characterize leptospirosis has provided clues about how an environmental organism might evolve into an important human pathogen.
Insights
The complete genome of virulent Leptospira interrogans was sequenced, revealing genes crucial for its evolution into a human pathogen. This provides insights into leptospirosis pathogenesis and potential therapeutic targets.
Area of Science:
- Microbiology
- Genomics
- Pathogen Evolution
Background:
- Leptospirosis is a significant global disease causing severe renal and hepatic damage.
- Virulent Leptospira interrogans serovar Lai is a key pathogen responsible for severe leptospirosis.
- Understanding the genetic basis of virulence is crucial for combating this disease.
Purpose of the Study:
- To determine the complete genomic sequence of Leptospira interrogans serovar Lai.
- To identify genes associated with virulence, pathogenesis, and host-pathogen interactions.
- To compare L. interrogans with other pathogenic spirochaetes.
Main Methods:
- Whole-genome sequencing of Leptospira interrogans serovar Lai.
- Bioinformatic analysis of the sequenced genome.
- Comparative genomics with Treponema pallidum and Borrelia burgdorferi.
Main Results:
- The genome comprises a large (4.33 Mb) and a small (359 kb) chromosome, totaling 4,768 predicted genes.
- Significant genetic differences exist between L. interrogans and other spirochaetes, with shared genes for morphological features.
- Identified genes related to chemotaxis, motility, lipopolysaccharide synthesis, adhesion, invasion, and hematological changes.
Conclusions:
- The genomic data provides a foundation for studying Leptospira virulence and pathogenesis.
- Specific genes identified offer clues into the evolution of L. interrogans as a human pathogen.
- This research paves the way for developing novel strategies against leptospirosis.
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