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Title:   Author  item
                                            Nicholson, Tracyitem
                                            Brockmeier, Susanitem
                                            Loving, Crystalitem
                                            Register, Karenitem
                                            Kehrli Jr, Marcusitem
                                            Shore, Sarah
  Submitted to: Infection and Immunity
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 12/15/2013
                                    Publication  Date: 3/4/2014
                                    Citation: Nicholson, T.L., Brockmeier, S.L., Loving, C.L., Register, K.B., Kehrli, Jr., M.E., Shore, S.M. 2014. The Bordetella bronchiseptica type III secretion system is required for persistence and disease severity but not transmission in swine. Infection and Immunity. 82(3):1092-1103.Interpretive Summary: Bordetella bronchiseptica is a bacterium that is widespread in swine herds and plays multiple roles in respiratory disease, causing both upper-respiratory illness and pneumonia, and predisposes pigs to infection with other bacteria. The type III secretion system (T3SS) is a needle-like structure that the bacterium uses to inject proteins directly into host cells to aid in the infection process. We constructed a mutant of B. bronchiseptica that does not make the T3SS to determine what role this system plays in colonizing the respiratory tract, causing disease, and transmitting pig-to-pig. Infection with the Bordetella T3SS mutant was cleared more rapidly, indicating the T3SS is required for the bacteria to persist in the pig’s respiratory tract. Additionally, disease was milder in pigs infected with the Bordetella T3SS mutant. The presence of the T3SS was found to hinder the pig’s immune response to Bordetella, which likely plays a role in the inability of swine to clear the bacteria and is why Bordetella can normally persist in the swine respiratory tract for long periods of time. However, the T3SS mutant was still capable of transmitting from one pig to another, demonstrating that even with minimal disease and lower colonization transmission can occur. Targeting proteins secreted by the T3SS for future vaccines will decrease disease caused by Bordetella and potentially reduce secondary bacterial infections as a result of infection with this bacteria.
                                Technical Abstract: Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Most studies addressing virulence factors of B. bronchiseptica utilize isolates derived from hosts other than pigs in conjunction with rodent infection models. Based on previous in vivo mouse studies, we hypothesized that the B. bronchiseptica type III secretion system (T3SS) would be required for maximal disease severity and persistence in the swine lower respiratory tract. To examine the contribution of the T3SS to the pathogenesis of B. bronchiseptica in swine, we compared the ability of a virulent swine isolate and an isogenic T3SS mutant to colonize, cause disease, and transmit host-to-host. We found the T3SS is required for maximal persistence throughout the swine respiratory tract, including the nasal cavity. Additionally, the T3SS contributes significantly to the development of nasal lesions and pneumonia. However, the T3SS mutant and the wild-type parent are equally capable of transmission among swine by both direct and indirect routes, demonstrating that transmission can occur even with attenuated disease. Our data further suggest the T3SS skews the adaptive immune response in swine by hindering the development of serum anti-Bordetella antibody levels and inducing an IL-10 cell-mediated response, likely contributing to the persistence of B. bronchiseptica in the respiratory tract. Overall, our results demonstrate that the Bordetella T3SS is required for maximal persistence and disease severity in pigs, but not for transmission.


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