Abstract
Listeria monocytogenes (Lm) is a widespread environmental Gram-positive bacterium that can
transition into a pathogen following ingestion by a susceptible host. To cross host barriers and
establish infection, Lm is dependent upon the regulated secretion and activity of many proteins
including PrsA2, a peptidyl-prolyl cis-trans isomerase with foldase activity. PrsA2 contributes to
the stability and activity of a number of secreted virulence factors that are required for Lm
invasion, replication, and cell-to-cell spread within the infected host. In contrast, a second related
secretion chaperone, PrsA1, has thus far no identified contributions to Lm pathogenesis. Here we
describe the characterization of a two-component signal transduction system PieRS that regulates
the expression of a regulon that includes the secretion chaperones PrsA1 and PrsA2. PieRS
regulated gene products are required for bacterial resistance to ethanol exposure and are
important for bacterial survival during transit through the gastrointestinal tract. PrsA1 was also
found to make a unique contribution to Lm survival in the GI tract, revealing for the first time a
non-overlapping requirement for both secretion chaperones PrsA1 and PrsA2 during the process
of intra-gastric infection.