Control of bacterial virulence through the peptide signature of the habitat

Emilia Krypotou, Mariela Scortti, Christin Grundström, Melanie Oelker, Ben F Luisi, Elisabeth Sauer-Eriksson, Jose Vazquez-Boland

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

To 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.
Original languageEnglish
Pages (from-to)1815-1827.e5
Number of pages18
JournalCell Reports
Issue number7
Early online date12 Feb 2019
Publication statusPublished - 12 Feb 2019


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