Abstract
Listeria monocytogenes is a Gram-positive facultative intracellular bacterial pathogen that invades mammalian cells and escapes from membrane-bound vacuoles to replicate within the host cell cytosol. Gene products required for intracellular bacterial growth and bacterial spread to adjacent cells are regulated by a transcriptional activator known as PrfA. PrfA becomes activated following L. monocytogenes entry into host cells, however the signal that stimulates PrfA activation has not yet been defined. Here we provide evidence for L. monocytogenes secretion of a small peptide pheromone, pPplA, which enhances the escape of L. monocytogenes from host cell vacuoles and may facilitate PrfA activation. The pPplA pheromone is generated via the proteolytic processing of the PplA lipoprotein secretion signal peptide. While the PplA lipoprotein is dispensable for pathogenesis, bacteria lacking the pPplA pheromone are significantly attenuated for virulence in mice and have a reduced efficiency of bacterial escape from the vacuoles of nonprofessional phagocytic cells. Mutational activation of PrfA restores virulence and eliminates the need for pPplA-dependent signaling. Experimental evidence suggests that the pPplA peptide may help signal to L. monocytogenes its presence within the confines of the host cell vacuole, stimulating the expression of gene products that contribute to vacuole escape and facilitating PrfA activation to promote bacterial growth within the cytosol.
Highlights
It has become increasingly apparent that bacteria do not exist as isolated, single celled organisms but instead have evolved a variety of communication systems that enable them to interact with other bacterial cells within a population
Grampositive bacteria rely on the secretion of small peptide pheromones to coordinate activities that include biofilm formation, exogenous DNA uptake via competence mechanisms, conjugal transfer of plasmid DNA, and expression of gene products that promote bacterial virulence
We provide evidence of a novel use of bacterial peptide pheromone signaling, that being the use of the pPplA peptide by L. monocytogenes to detect the confines of host
Summary
It has become increasingly apparent that bacteria do not exist as isolated, single celled organisms but instead have evolved a variety of communication systems that enable them to interact with other bacterial cells within a population. Limited information has far been available regarding the use of peptide pheromone sensing to coordinate cellular functions of the Gram-positive environmental pathogen Listeria monocytogenes [5,6,7,8,9]. This bacterium survives as a saprophyte in soil but is capable of transitioning into life as an intracellular pathogen following ingestion by susceptible mammalian hosts [10,11,12,13,14,15]. It has been postulated that L. monocytogenes senses environmental cues that inform the bacterium as to its intracellular location [13]
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