Affiliation:
1. Institute for Medical Microbiology and Hygiene, University Hospital Tübingen, Elfriede-Aulhornstr. 6, Tübingen D-72076, Germany
2. Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena D-07745, Germany
3. Max Planck Institute for Developmental Biology, Department Protein Evolution, Spemannstr. 35-39, Tübingen D-72076, Germany
Abstract
ABSTRACT
Yersinia
adhesin A (YadA) is a trimeric autotransporter adhesin with multiple functions in host-pathogen interactions. The aim of this study was to dissect the virulence functions promoted by YadA
in vitro
and
in vivo
. To accomplish this, we generated
Yersinia enterocolitica
O:8 mutants expressing point mutations in YadA G389, a highly conserved residue in the membrane anchor of YadA, and analyzed their impact on YadA expression and virulence functions. We found that point mutations of YadA G389 led to impaired transport, stability, and surface display of YadA. YadA G389A and G389S mutants showed comparable YadA surface expression, autoagglutination, and adhesion to those of wild-type YadA but displayed reduced trimer stability and complement resistance
in vitro
and were 10- to 1,000-fold attenuated in experimental
Y. enterocolitica
infection in mice. The G389T, G389N, and G389H mutants lost trimer stability, exhibited strongly reduced surface display, autoagglutination, adhesion properties, and complement resistance, and were avirulent (>10,000-fold attenuation) in mice. Our data demonstrate that G389 is a critical residue of YadA, required for optimal trimer stability, transport, surface display, and serum resistance. We also show that stable trimeric YadA protein is essential for virulence of
Y. enterocolitica
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference50 articles.
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