Open AccessSifA permits survival and replication of Salmonella typhimurium in murine macrophages
Author(s) -
Brumell John H.,
Rosenberger Carrie M.,
Gotto Geoffrey T.,
Marcus Sandra L.,
Finlay B. Brett
Publication year - 2001
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1046/j.1462-5822.2001.00087.x
Subject(s) - biology , effector , secretion , mutant , microbiology and biotechnology , transfection , vacuole , virulence , type three secretion system , salmonella , endosome , cytoplasm , cell culture , gene , genetics , bacteria , biochemistry , intracellular
SifA was originally identified as a virulence factor required for formation of Salmonella ‐induced filaments (Sifs), elongated tubules rich in lysosomal glycoproteins that extend from the Salmonella ‐containing vacuole in infected epithelial cells. Here, we demonstrate that deletion mutants of ssaR , a component of the SPI‐2 type III secretion system, do not form Sifs in HeLa epithelial cells. This suggests that SifA is a translocated effector of this system, acting within host cells to form Sifs. In support of this hypothesis, transfection of HeLa cells with a vector encoding SifA fused to the green fluorescent protein caused extensive vacuolation of LAMP‐1‐positive compartments. Filamentous tubules that closely resembled Sifs were also observed in transfected cells, demonstrating that SifA is sufficient to initiate alteration of host cell endosomal structures. Δ sifA mutants were impaired in their ability to survive/replicate in RAW 264.7 murine macrophages, a phenotype similar to ssaR mutants. Our findings suggest that SifA is an effector of the SPI‐2 type III secretion system and allows colonization of murine macrophages, the host niche exploited during systemic phases of disease in these animals. A family of SifA‐related proteins and their importance to Salmonella pathogenesis is also discussed.