High-Temperature Protein G Is an Essential Virulence Factor of Leptospira interrogans

Abstract

Leptospira interrogans is a global zoonotic pathogen and is the causative agent of leptospirosis, an endemic disease of humans and animals worldwide. There is limited understanding of leptospiral pathogenesis and further elucidation of the mechanisms involved would therefore aid in vaccine development and prevention of infection. HtpG (High temperature protein G) is the bacterial homolog to the highly conserved molecular chaperone Hsp90, and is important in the stress response of many bacteria. The specific role of HtpG, especially in bacterial pathogenesis, remains largely unknown. Through the use of an L. interrogans htpG transposon insertion mutant, this study demonstrates that HtpG of L. interrogans is essential for virulence in the hamster model of acute leptospirosis. Complementation of the htpG mutant completely restored virulence. Surprisingly, the htpG mutant did not appear to show sensitivity to heat or oxidative stress, phenotypes common in htpG mutants in other bacterial species. Furthermore, the mutant did not show increased sensitivity to serum complement, reduced survival within macrophages, nor altered protein or lipopolysaccharide expression. The underlying cause for attenuation thus remains unknown, but HtpG is a novel leptospiral virulence factor, and one of only a very small number identified to date.