IAI Accepts, published online ahead of print on 23 February 2009

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Infect. Immun. doi:10.1128/IAI.01162-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Yersinia pestis IS1541 transposition provides for escape from plague immunity

Claire A. Cornelius, Lauriane E. Quenee, Derek Elli, Nancy A. Ciletti, and Olaf Schneewind^*

Department of Microbiology, University of Chicago, IL60637, USA

^* To whom correspondence should be addressed. Email: oschnee{at}bsd.uchicago.edu.

Yersinia pestis is perhaps the most feared infectious agent due to its ability of causing epidemic outbreaks of plague disease in animals and humans with high mortality. Plague infections elicit strong humoral immune responses against the capsular antigen (F1, fraction 1) of Yersinia pestis and F1-specific antibodies provide protective immunity. Here we asked whether Y. pestis generates mutations that enable bacterial escape from protective immunity and isolated a variant with an IS1541 insertion in caf1A, encoding the F1 outer membrane usher. The caf1A::IS1541 insertion prevented assembly of F1 pili and provided escape from plague immunity via F1-specific antibodies without reduction of virulence in mouse models of bubonic or pneumonic plague. F1-specific antibodies interfere with Y. pestis type III transport of effector proteins into host cells, an inhibitory effect that was overcome by the caf1A::IS1541 insertion. These findings suggest a model whereby IS1541 insertion in caf1A provides for reversible changes in envelope structure, enabling Y. pestis escape from adaptive immune responses and plague immunity.