High-Temperature Protein G Is an Essential Virulence Factor of

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; therefore, further elucidation of the mecha-nisms involved would aid in vaccine development and the prevention of infection. HtpG (high-temperature proteinG) is the bac-terial homolog to the highly conserved molecular chaperone Hsp90 and is important in the stress responses 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 L. interrogansHtpG is essential for virulence in the hamster model of acute leptospirosis. Complementation of the htpGmutant completely restored virulence. Surprisingly, the htpGmu-tant did not appear to show sensitivity to heat or oxidative stress, phenotypes common in htpGmutants in other bacterial spe-cies. Furthermore, the mutant did not show increased sensitivity to serum complement, reduced survival within macrophages, or 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. Leptospira interrogans is a global zoonotic pathogen that infectsa wide variety of hosts, including humans, domestic animals, and rodents (1, 2). Leptospirosis is a systemic infection transmit-ted to susceptible hosts via contact with contaminated water or soil, or by direct contact with urine or other tissues of infecte