IAI Accepts, published online ahead of print on 19 October 2009

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Infect. Immun. doi:10.1128/IAI.00559-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Absence of inflammation and pneumonia during infection with non-pigmented Yersinia pestis reveals new role for the pgm locus in pathogenesis

Hanni Lee-Lewis and Deborah M. Anderson^*

Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri

^* To whom correspondence should be addressed. Email: andersondeb{at}missouri.edu.

Yersinia pestis causes primary pneumonic plague in many mammalian species, including humans, mice and rats. Virulent Y. pestis strains undergo frequent spontaneous deletion of a 102kb chromosomal DNA fragment, known as the pigmentation (pgm) locus, when grown in laboratory media, yet this locus is present in every virulent isolate. The pgm locus encodes siderophore biosynthesis genes within a high pathogenicity island that are required for growth in the mammalian host when inoculated by peripheral routes. Recently, higher challenge doses of non-pigmented Y. pestis were reported to cause fatal pneumonic plague in mice suggesting a useful model for studies of virulence and immunity. In this work, we show that intranasal infection of BALB/c mice with non-pigmented Yersinia pestis does not result in pneumonic plague. Despite persistent bacterial colonization within the lungs and eventual death of infected mice, pulmonary inflammation was generally absent and there was no disease pathology characteristic of pneumonic plague. Iron given to mice at the time of challenge, previously shown to enhance virulence of pgm-deficient strains, resulted in an accelerated disease course with less time to bacteremia and lethality, but lung inflammation and pneumonia were still absent. We examined other rodent models and found variation in lung inflammatory responses, some of which led to clearance and survival even when high challenge doses were used. Together, the results suggest that the Y. pestis pgm locus encodes previously unappreciated virulence factors required for the induction of pneumonic plague that are independent of iron scavenging from the mammalian host.