Intranasal Inoculation of Mice withYersinia pseudotuberculosisCauses a Lethal Lung Infection That Is Dependent onYersiniaOuter Proteins andPhoP

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Abstract
Yersinia pseudotuberculosisinfects many mammals and birds including humans, livestock, and wild rodents and can be recovered from the lungs of infected animals. To determine theY. pseudotuberculosisfactors important for growth during lung infection, we developed an intranasal model of infection in mice. Following intranasal inoculation, we monitored both bacterial growth in lungs and dissemination to systemic tissues. Intranasal inoculation with as few as 18 CFU ofY. pseudotuberculosiscaused a lethal lung infection in some mice. Over the course of 7 days, wild-typeY. pseudotuberculosisreplicated to nearly 1 × 108CFU/g of lung in BALB/c mice, induced histopathology in lungs consistent with pneumonia, but disseminated sporadically to other tissues. In contrast, a ΔyopBdeletion strain was attenuated in this model, indicating that translocation ofYersiniaouter proteins (Yops) is essential for virulence. Additionally, a ΔyopHnull mutant failed to grow to wild-type levels by 4 days postintranasal inoculation, but deletions of any other single effector YOP did not attenuate lung colonization 4 days postinfection. Strains with deletions inyopHand any one of the other known effectoryopgenes were more attenuated that the ΔyopHstrain, indicating a unique role foryopHin lungs. In summary, we have characterized the progression of a lung infection with an entericYersiniapathogen and shown that YopB and YopH are important in lung colonization and dissemination. Furthermore, this lung infection model withY. pseudotuberculosiscan be used to test potential therapeutics againstYersiniaand other gram-negative infections in lungs.