Pathogenesis of leptospirosis: The influence of genomics

Leptospirosis is the most widespread zoonosis worldwide and is caused by serovars of pathogenic Leptospira species. The understanding of leptospiral pathogenesis lags far behind that of many other bacterial pathogens. Current research is thus directed at identification of leptospiral virulence factors. Saprophytic Leptospira species are environmental organisms that never cause disease. Comparative genomics of pathogens and saprophytes has allowed the identification of more than 900 genes unique to either Leptospira interrogans or Leptospira borgpetersenii; these genes potentially encode virulence-associated proteins. However, genes of unknown function are over-represented in this subset of pathogen-specific genes, accounting for 80 and 60 of open reading frames, respectively. This finding, together with the absence of virulence factor homologues among the proteins of known function, suggests that Leptospira possesses unique virulence mechanisms. Whole genome microarray studies have identified genes whose expression is differentially regulated under a range of simulated in vivo conditions, such as physiological temperature and osmolarity, low iron levels, and the presence of serum. The subset of genes identified by these studies is likely to include virulence factors. However, most such genes encode proteins of unknown function, consistent with the hypothesis that leptospiral virulence genes do not have homologues in other bacterial species. The recent development of...