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Gene Review:

sifA - secreted effector protein SifA

Salmonella enterica subsp. enterica serovar Typhimurium str. LT2

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Disease relevance of sifA

Salmonella enterica serovar Typhimurium interaction with dendritic cells: impact of the sifA gene [1].

High impact information on sifA

A sifA(-) mutant strain had a replication defect in macrophages, similar to that of SPI-2 and ompR(-) mutant strains [2].
In mouse macrophages, sifA Delta 6 mutant bacteria displayed a reduced association with vacuolar markers, similar to that of sifA null mutant bacteria, and exhibited a dramatic replication defect [3].
Deletion mutant strains in sifA or in the downstream potC were constructed [4].
Collectively, these results suggest that sifA arose by horizontal gene transfer into Salmonella and its product is involved in a virulence-associated intracellular phenotype related to Salmonella-induced filament formation [4].
Delta sifA does not produce Salmonella-induced filaments in epithelial cells, and is attenuated in mice [4].

Biological context of sifA

Fourteen-base-pair direct repeats mark the probable site of integration of sifA and its flanking DNA have a significantly reduced G+C content (41%) when compared with the potABCD operon (51%) and the Salmonella genome (52-54%) [4].

Anatomical context of sifA

Here we demonstrate that enhanced replication of sifA mutants occurs in the cytosol of these cells [5].
In this study a Salmonella strain carrying a mutation in sifA which is released from the vacuole was used to analyse Salmonella survival and replication within the cytosol of several cell lines [6].

Other interactions of sifA

Mutations in various SPI2 effector (sifA and sseEFG) and structural (ssaV) genes were then analysed in the BER mutant background [7].
In this work, immunoblotting and flow cytometry were used to analyse the roles of SsrA-B and OmpR-EnvZ in coupling different environmental signals to changes in expression of a SPI-2 TTSS translocon component (SseB) and two effector genes (sifA and sifB) [8].
We tested two new strains of Salmonella typhimurium, one carrying a mutation in a SPI-2 gene and the aroC-gene and another carrying mutations in the sifA- and aroC-genes, as potential DNA vaccine delivery vehicles [9].

References

Salmonella enterica serovar Typhimurium interaction with dendritic cells: impact of the sifA gene. Petrovska, L., Aspinall, R.J., Barber, L., Clare, S., Simmons, C.P., Stratford, R., Khan, S.A., Lemoine, N.R., Frankel, G., Holden, D.W., Dougan, G. Cell. Microbiol. (2004) [Pubmed]
Salmonella maintains the integrity of its intracellular vacuole through the action of SifA. Beuzón, C.R., Méresse, S., Unsworth, K.E., Ruíz-Albert, J., Garvis, S., Waterman, S.R., Ryder, T.A., Boucrot, E., Holden, D.W. EMBO J. (2000) [Pubmed]
Salmonella typhimurium SifA effector protein requires its membrane-anchoring C-terminal hexapeptide for its biological function. Boucrot, E., Beuzón, C.R., Holden, D.W., Gorvel, J.P., Méresse, S. J. Biol. Chem. (2003) [Pubmed]
Identification of a Salmonella virulence gene required for formation of filamentous structures containing lysosomal membrane glycoproteins within epithelial cells. Stein, M.A., Leung, K.Y., Zwick, M., Garcia-del Portillo, F., Finlay, B.B. Mol. Microbiol. (1996) [Pubmed]
Disruption of the Salmonella-containing vacuole leads to increased replication of Salmonella enterica serovar typhimurium in the cytosol of epithelial cells. Brumell, J.H., Tang, P., Zaharik, M.L., Finlay, B.B. Infect. Immun. (2002) [Pubmed]
Growth and killing of a Salmonella enterica serovar Typhimurium sifA mutant strain in the cytosol of different host cell lines. Beuzón, C.R., Salcedo, S.P., Holden, D.W. Microbiology (Reading, Engl.) (2002) [Pubmed]
DNA base excision repair potentiates the protective effect of Salmonella Pathogenicity Island 2 within macrophages. Suvarnapunya, A.E., Stein, M.A. Microbiology (Reading, Engl.) (2005) [Pubmed]
The roles of SsrA-SsrB and OmpR-EnvZ in the regulation of genes encoding the Salmonella typhimurium SPI-2 type III secretion system. Garmendia, J., Beuzón, C.R., Ruiz-Albert, J., Holden, D.W. Microbiology (Reading, Engl.) (2003) [Pubmed]
Novel strains of Salmonella typhimurium as potential vectors for gene delivery. Michael, A., Stratford, R., Khan, S., Dalgleish, A., Pandha, H. FEMS Microbiol. Lett. (2004) [Pubmed]

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