Resumo

Introduction: Protein secretion systems constitute one of diverse bacterial pathogenesis mechanisms. To date, a new secretion system has been described (Type VI Secretion System, T6SS)widely distributed among Gram-negative bacteria that come in close contact with eukaryotic cells. This is the case of Salmonella enterica, a species with more than 2,500 serovars associated with a variety of diseases in human and other vertebrates. Although T6SSs are present in a great number of bacterial pathogens their relevance in Salmonella pathogenesis have been poorly studied. A genome-wide in silico analysis of T6SS in the genus Salmonella revealed the presence of T6SSs encoded in genomic islands differentially distributed among serovars. For instance, S. Typhimurium harbors only the T6SS encoded in SPI-6, while S. Dublin carries two T6SSs encoded in SPI-6 and SPI-19, respectively. Hence, the differential distribution of these T6SS gives a chance to study their contribution to Salmonella pathogenesis. Methods: To determine whether T6SSs encoded in SPI-6 and SPI-19 contribute to colonization and systemic infection of S. Typhimurium and S. Dublin, competition assays using different 1:1 mixes between deletion mutants, in one or both systems, and their respective wild type strains were performed in murine and avian infection models. Results: Our results show that T6SS encoded in SPI-6 contributes to murine and avian colonization since T6SS and clpV mutants are recovered in significantly lower numbers than wild type strains of Typhimurium and Dublin during the infection of both mice and chickens. Interestingly, the colonization defect observed for ΔT6SSSPI-6 strains is reverted by complementation in trans with their own T6SSSPI-6 as well as T6SSSPI-6 of the other serovar in both infection models, suggesting that T6SS encoded in SPI-6 is functional regardless of the genetic background. On the other hand, T6SS encoded in SPI-19 does not play a role in avian or murine colonization during S. Dublin infection; nevertheless the presence of T6SSSPI-19 in S. Typhimurium complements the colonization defect of ΔT6SSSPI-6 observed in mice and confers a selective advantage during the initial steps of avian colonization. Conclusions: In summary, our results suggest that T6SS of SPI-6 constitutes a molecular mechanism of pathogenicity widely distributed among Salmonella enterica serovars that is required for infection of different animal hosts. It is tempting to speculate that the differential distribution of T6SS in S. enterica corresponds to an evolutionary process that contributed to specific adaptation to different hosts.