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      YqiC of Salmonella enterica serovar Typhimurium is a membrane fusogenic protein required for mice colonization

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          Abstract

          Background

          Salmonella enterica serovar Typhimurium is an intracellular bacterial pathogen which can colonize a variety of hosts, including human, causing syndromes that vary from gastroenteritis and diarrhea to systemic disease.

          Results

          In this work we present structural information as well as insights into the in vivo function of YqiC, a 99-residue protein of S. Typhimurium, which belongs to the cluster of the orthologous group 2960 (COG2960). We found that YqiC shares biophysical and biochemical properties with Brucella abortus BMFP, the only previously characterized member of this group, such as a high alpha helix content, a coiled-coil domain involved in trimerization and a membrane fusogenic activity in vitro. In addition, we demonstrated that YqiC localizes at cytoplasmic and membrane subcellular fractions, that a S. Typhimurium yqiC deficient strain had a severe attenuation in virulence in the murine model when inoculated both orally and intraperitoneally, and was impaired to replicate at physiological and high temperatures in vitro, although it was still able to invade and replicate inside epithelial and macrophages cell lines.

          Conclusion

          This work firstly demonstrates the importance of a COG2960 member for pathogen-host interaction, and suggests a common function conserved among members of this group.

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          Most cited references27

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          Salmonella maintains the integrity of its intracellular vacuole through the action of SifA.

          A method based on the Competitive Index was used to identify Salmonella typhimurium virulence gene interactions during systemic infections of mice. Analysis of mixed infections involving single and double mutant strains showed that OmpR, the type III secretion system of Salmonella pathogenicity island 2 (SPI-2) and SifA [required for the formation in epithelial cells of lysosomal glycoprotein (lgp)-containing structures, termed Sifs] are all involved in the same virulence function. sifA gene expression was induced after Salmonella entry into host cells and was dependent on the SPI-2 regulator ssrA. A sifA(-) mutant strain had a replication defect in macrophages, similar to that of SPI-2 and ompR(-) mutant strains. Whereas wild-type and SPI-2 mutant strains reside in vacuoles that progressively acquire lgps and the vacuolar ATPase, the majority of sifA(-) bacteria lost their vacuolar membrane and were released into the host cell cytosol. We propose that the wild-type strain, through the action of SPI-2 effectors (including SpiC), diverts the Salmonella-containing vacuole from the endocytic pathway, and subsequent recruitment and maintenance of vacuolar ATPase/lgp-containing membranes that enclose replicating bacteria is mediated by translocation of SifA.
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            pBBR1MCS: a broad-host-range cloning vector.

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              Special delivery: vesicle trafficking in prokaryotes.

              Although the observation that Gram-negative bacteria produce outer membrane vesicles (MVs) was made over 40 years ago, their biological roles have become a focus of study only within the past 10 years. Recent progress in this area has revealed that bacterial MVs are utilized for several processes including delivery of toxins to eukaryotic cells, protein and DNA transfer between bacterial cells, and trafficking of cell-cell signals. Some of these roles appear to be generalized among the Gram-negative bacteria while others are restricted to specific bacterial species/strains. Here we review the known roles of MVs, propose other roles for MVs in mediating interspecies and inter-kingdom communication, and discuss the mechanism of MV formation.
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                Author and article information

                Journal
                BMC Microbiol
                BMC Microbiology
                BioMed Central
                1471-2180
                2011
                9 May 2011
                : 11
                : 95
                Affiliations
                [1 ]Instituto de Biotecnología, CICVyA-INTA Castelar, Los Reseros y Las Cabañas s/n, Buenos Aires, Argentina
                [2 ]Fundación Instituto Leloir (IIBBA-CONICET), Av. Patricias Argentinas 435, Buenos Aires, Argentina
                [3 ]Instituto de Biología Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Argentina
                Article
                1471-2180-11-95
                10.1186/1471-2180-11-95
                3107778
                21554724
                1f806de3-351f-4735-9cf0-d98b89cbf64f
                Copyright ©2011 Carrica et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 January 2011
                : 9 May 2011
                Categories
                Research Article

                Microbiology & Virology
                Microbiology & Virology

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