title: 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; therefore, further elucidation of the mechanisms involved would aid in vaccine development and the 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 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. interrogans HtpG 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, 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.
authors.affiliation: Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Victoria, Australia.
authors.forename: Amy M
authors.initials: AM
authors.lastname: King
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pretre
authors.forename: Thanatchaporn
authors.initials: T
authors.lastname: Bartpho
authors.forename: Rasana W
authors.initials: RW
authors.lastname: Sermswan
authors.forename: Claudia
authors.initials: C
authors.lastname: Toma
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Azad
authors.initials: A
authors.lastname: Eshghi
authors.forename: Mathieu
authors.initials: M
authors.lastname: Picardeau
authors.forename: Ben
authors.initials: B
authors.lastname: Adler
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Murray
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D019295:Computational Biology; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007921:Leptospira interrogans / Q000235:genetics / Q000276:immunology*; D007922:Leptospirosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008647:Mesocricetus / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009997:Osmotic Pressure; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology; D013696:Temperature; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D018841:HSP90 Heat-Shock Proteins; D037521:Virulence Factors; C066720:HtpG protein, bacteria