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The Salmonella effector AvrA mediates bacterial intracellular survival during infection
Author(s) -
Wu Huixia,
Jones Rheinallt,
Neish Andrew
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.117.5
Subject(s) - effector , salmonella , biology , microbiology and biotechnology , apoptosis , mutant , intracellular , intracellular parasite , spleen , immunology , bacteria , biochemistry , gene , genetics
The enteric pathogen Salmonella typhimurium secretes the preformed effector AvrA into host cells. This acetyltransferase has been shown to suppress intestinal immune and apoptotic responses by inhibition of JNK MAPK. To study the role of AvrA in natural enteric infection, we used a mouse model to compare wild type Salmonella to an isogenic AvrA null mutant. Salmonella lacking AvrA induced increased neutrophil infiltration in the gut, more intense systemic cytokine responses, and higher apoptosis in epithelial cells. Mice infected with an AvrA‐ mutant also showed higher bacterial burden in liver, spleen, and mesenteric lymph nodes. Furthermore, the mice exhibited more severe apoptosis in macrophages within those tissues. Consistently, in vitro primary epithelial cells and mouse bone marrow derived macrophages infected with AvrA‐ mutant Salmonella also showed higher apoptosis relative to wild type bacteria. To study the mechanisms involved, recombinant adenoviruses expressing AvrA were constructed. AvrA transduced into epithelial cells and macrophages protected the cells from an external proapoptotic signal. In conclusion, the results suggest AvrA suppresses apoptosis in infected host cells, which may allow for establishment of a stable niche typical of intracellular pathogens.