Control of Bacterial Virulence through the Peptide Signature of the Habitat

Publication date: 12 February 2019Source: Cell Reports, Volume 26, Issue 7Author(s): Emilia Krypotou, Mariela Scortti, Christin Grundström, Melanie Oelker, Ben F. Luisi, A. Elisabeth Sauer-Eriksson, José Vázquez-BolandSummaryTo optimize fitness, pathogens selectively activate their virulence program upon host entry. Here, we report that the facultative intracellular bacterium Listeria monocytogenes exploits exogenous oligopeptides, a ubiquitous organic N source, to sense the environment and control the activity of its virulence transcriptional activator, PrfA. Using a genetic screen in adsorbent-treated (PrfA-inducing) medium, we found that PrfA is functionally regulated by the balance between activating and inhibitory nutritional peptides scavenged via the Opp transport system. Activating peptides provide essential cysteine precursor for the PrfA-inducing cofactor glutathione (GSH). Non-cysteine-containing peptides cause promiscuous PrfA inhibition. Biophysical and co-crystallization studies reveal that peptides inhibit PrfA through steric blockade of the GSH binding site, a regulation mechanism directly linking bacterial virulence and metabolism. L. monocytogenes mutant analysis in macrophages and our functional data support a model in which changes in the balance of antagonistic Opp-imported oligopeptides promote PrfA induction intracellularly and PrfA repression outside the host.Graphical Abstract

Source: Cell Reports - February 13, 2019 Category: Cytology Source Type: research