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Title:   Author  item
                                            Nicholson, Tracyitem
                                            Brockmeier, Susanitem
                                            Loving, Crystalitem
                                            Register, Karenitem
                                            Kehrli Jr, Marcusitem
                                            STIBITZ, SCOTT - Food And Drug Administration(FDA)item
                                            Shore, Sarah
  Submitted to: Infection and Immunity
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 12/12/2011
                                    Publication  Date: 3/1/2012
                                    Citation: Nicholson, T.L., Brockmeier, S.L., Loving, C.L., Register, K.B., Kehrli, Jr., M.E., Stibitz, S.E., Shore, S.M. 2012. Phenotypic modulation of the virulent Bvg phase is not required for pathogenesis and transmission of Bordetella bronchiseptica in swine. Infection and Immunity. 80(3):1025-1036.Interpretive Summary: The porcine respiratory disease complex (PRDC) is a multifactorial disease complex of swine caused by numerous viruses, bacteria and adverse environmental conditions. In its various forms PRDC is the most costly problem to the swine producer today. Bordetella bronchiseptica is a bacterial pathogen that causes respiratory disease in pigs on its own and predisposes to secondary invasion of other pathogenic bacteria. This bacterium is able to regulate its gene expression to favor expression of certain genes when it encounters a host and others when it is in the environment. We examined whether the ability to transition between these two phases was necessary for the bacterium to cause disease and transmit from one pig to another either directly or through the air. B. bronchiseptica bacteria "locked" in an environmental phase are unable to infect pigs while bacteria "locked" in the host phase do not survive in the environment. However, bacteria locked in the host phase are able to cause disease and transmit directly between pigs as well as indirectly through the air, never requiring transition to the environmental phase. These results will help in rational design of vaccine candidates and transmission intervention strategies in swine herds.
                                Technical Abstract: The majority of virulence gene expression in Bordetella is regulated by a two-component sensory transduction system encoded by the bvg locus. In response to environmental cues, the BvgAS regulatory system controls expression of a spectrum of phenotypic phases transitioning between a virulent (Bvg+) phase and a non-virulent (Bvg¬-) phase, a process referred to as phenotypic modulation. We hypothesized that the ability of B. bronchiseptica to undergo phenotypic modulation is required at one or more points during the infectious cycle in swine. To investigate the Bvg phase-dependent contribution to pathogenesis of B. bronchiseptica in swine, we constructed a series of isogenic mutants in a virulent B. bronchiseptica swine isolate and compared each mutant to the wild-type isolate, for its ability to colonize and cause disease. We additionally tested whether a BvgAS system capable of modulation is required for direct or indirect transmission. The Bvg¬- phase-locked mutant was never recovered from any respiratory tract site at any time point examined. The Bvg**i phase-locked mutant was found in numbers lower than wild-type at all respiratory tract sites and time points examined and caused limited to no disease. In contrast, colonization of the respiratory tract and disease caused by the Bvg+ phase-locked mutant and the wild-type strain were indistinguishable. The Bvg+ phase-locked mutant transmitted to naive pigs by both direct and indirect contact with equal efficiency as the wild-type isolate. These results indicate that while full activation of the BvgAS regulatory system is required for colonization and severe disease, it is not deleterious to direct and indirect transmission. Overall, our results demonstrate that the Bvg+ phase is sufficient for respiratory infection and host-to-host transmission of B. bronchiseptica in swine.


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