Characterization of the <i>Listeria monocytogenes</i> PieRS regulon distinguishes the function of the critical secretion chaperone PrsA2 from other regulon members

<i>Listeria monocytogenes</i> (<i>Lm</i>) is a gram-positive pathogen that is widespread throughout the environment and known for its ability to infect mammalian hosts following the ingestion of contaminated food. <i>Lm</i> uses a variety of mechanisms to survive challenging conditions experienced both during life in the outside environment and inside of the infected host. We recently described a novel two-component signaling system known as PieRS that regulates the secretion of the chaperone PrsA2, which is essential for bacterial virulence, as well as its related homolog PrsA1 and a variety of gene products of unknown function. Here, we examine the roles of the less characterized PieRS-regulated gene products and contrast their functions with PrsA2 in terms of bacterial survival under stress conditions and virulence in mice. Characterization of targeted in-frame deletion mutants of PieRS regulon members indicates-in contrast to <i>prsA2</i> mutants-minimal contributions to stress survival and bacterial virulence. Modest contributions of select regulon members were associated with <i>Lm</i> colonization of the gastrointestinal tract. The PieRS regulon thus consists of gene products that contribute to <i>Lm</i> physiology in ways that are clearly distinct from PrsA2 and the chaperone's essential function for both stress survival and bacterial virulence.