The Yersinia pestis GTPase BipA Promotes Pathogenesis of Primary Pneumonic Plague
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Samantha D. Crane, Srijon K. Banerjee, Kara R. Eichelberger, Richard C. Kurten, William E. Goldman, Roger Pechous
Abstract
<jats:title>ABSTRACT</jats:title>
<jats:named-content content-type="genus-species">Yersinia pestis</jats:named-content> is a highly virulent pathogen and the causative agent of bubonic, septicemic, and pneumonic plague. Primary pneumonic plague caused by inhalation of respiratory droplets contaminated with <jats:named-content content-type="genus-species">Y. pestis</jats:named-content> is nearly 100% lethal within 4 to 7 days without antibiotic intervention. Pneumonic plague progresses in two phases, beginning with extensive bacterial replication in the lung with minimal host responsiveness, followed by the abrupt onset of a lethal proinflammatory response. The precise mechanisms by which <jats:named-content content-type="genus-species">Y. pestis</jats:named-content> is able to colonize the lung and survive two very distinct disease phases remain largely unknown. To date, a few bacterial virulence factors, including the Ysc type 3 secretion system, are known to contribute to the pathogenesis of primary pneumonic plague. The bacterial GTPase BipA has been shown to regulate expression of virulence factors in a number of Gram-negative bacteria, including <jats:named-content content-type="genus-species">Pseudomonas aeruginosa</jats:named-content>, <jats:named-content content-type="genus-species">Escherichia coli</jats:named-content>, and <jats:named-content content-type="genus-species">Salmonella enterica</jats:named-content> serovar Typhi. However, the role of BipA in <jats:named-content content-type="genus-species">Y. pestis</jats:named-content> has yet to be investigated. Here, we show that BipA is a <jats:named-content content-type="genus-species">Y. pestis</jats:named-content> virulence factor that promotes defense against early neutrophil-mediated bacterial killing in the lung. This work identifies a novel <jats:named-content content-type="genus-species">Y. pestis</jats:named-content> virulence factor and highlights the importance of early bacterial/neutrophil interactions in the lung during primary pneumonic plague.
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