A Contingency Locus in prfA in a Listeria monocytogenes Subgroup Allows Reactivation of the PrfA Virulence Regulator during Infection in Mice

A nonhemolyticListeria monocytogenes strain isolated from a fish processing plant was avirulent in a plaque-forming assay and in a subcutaneous mouse virulence assay. However, it showed 60% lethality (9/15 mice) when 109 CFU were intraperitoneally injected into mice. HemolyticL. monocytogenes bacteria were recovered from liver and spleen of the deceased mice, and the pulsed-field gel electrophoresis patterns were indistinguishable for the nonhemolytic and the hemolytic isolates. Sequencing ofprfA from the nonhemolytic strain revealed a duplication of 7 bp in the helix-turn-helix region, resulting in a truncated PrfA protein. We propose that the direct repeat of 7 bp causes a reversible inactivation ofprfA and that slipped-strand mispairing regulates the phase variation in hemolytic activity and virulence. NonhemolyticL. monocytogenes strains with identical duplications inprfA were isolated from several sources in France, as well as in Norway, suggesting that the reversible inactivation described in this study is not an isolated event.