Listeria monocytogenes PrsA2 is required for virulence factor secretion and bacterial viability within the host cell cytosol.
In the course of establishing its replication niche within the cytosol of infected host cells, the facultative intracellular bacterial pathogen Listeria monocytogenes must efficiently regulate the secretion and activity of multiple virulence factors. L. monocytogenes encodes two predicted posttranslocation secretion chaperones, PrsA1 and PrsA2, and evidence suggests that PrsA2 has been specifically adapted for bacterial pathogenesis. PrsA-like chaperones have been identified in a number of Gram-positive bacteria, where they are reported to function at the bacterial membrane-cell wall interface to assist in the folding of proteins translocated across the membrane; in some cases, these proteins have been found to be essential for bacterial viability. In this study, the contributions of PrsA2 and PrsA1 to L. monocytogenes growth and protein secretion were investigated in vitro and in vivo. Neither PrsA2 nor PrsA1 was found to be essential for L. monocytogenes growth in broth culture; however, optimal bacterial viability was found to be dependent upon PrsA2 for L. monocytogenes located within the cytosol of host cells. Proteomic analyses of prsA2 mutant strains in the presence of a mutationally activated allele of the virulence regulator PrfA revealed a critical requirement for PrsA2 activity under conditions of PrfA activation, an event which normally takes place within the host cell cytosol. Despite a high degree of amino acid similarity, no detectable degree of functional overlap was observed between PrsA2 and PrsA1. Our results indicate a critical requirement for PrsA2 under conditions relevant to host cell infection.
Alonzo
Francis
F
Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612-7344, USA.
Freitag
Nancy E
NE
D000818:Animals; D001426:Bacterial Proteins; D002460:Cell Line; D003600:Cytosol / Q000382:microbiology*; D005260:Female; D005347:Fibroblasts / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology*; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D050296:Microbial Viability; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D037521:Virulence Factors; D019696:Peptidylprolyl Isomerase; C541924:PrsA2 protein, Listeria monocytogenes
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