PrgU: a suppressor of sex pheromone toxicity in Enterococcus faecalis

Minny Bhatty, Martha I. Camacho, Christian Gonzalez-Rivera, Kristi L. Frank, Jennifer L. Dale, Dawn A. Manias, Gary M. Dunny, Peter J. Christie

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Upon sensing of the peptide pheromone cCF10, Enterococcus faecalis cells carrying pCF10 produce three surface adhesins (PrgA, PrgB or Aggregation Substance, PrgC) and the Prg/Pcf type IV secretion system and, in turn, conjugatively transfer the plasmid at high frequencies to recipient cells. Here, we report that cCF10 induction is highly toxic to cells sustaining a deletion of prgU, a small orf located immediately downstream of prgB on pCF10. Upon pheromone exposure, these cells overproduce the Prg adhesins and display impaired envelope integrity, as evidenced by antibiotic susceptibility, misplaced division septa and cell lysis. Compensatory mutations in regulatory loci controlling expression of pCF10-encoded prg/pcf genes, or constitutive PrgU overproduction, block production of the Prg adhesins and render cells insensitive to pheromone. Cells engineered to overproduce PrgB, even independently of other pCF10-encoded proteins, have severely compromised cell envelopes and strong growth defects. PrgU has an RNA-binding fold, and prgB-prgU gene pairs are widely distributed among E. faecalis isolates and other enterococcal and staphylococcal species. Together, our findings support a model in which PrgU proteins represent a novel class of RNA-binding regulators that act to mitigate toxicity accompanying overproduction of PrgB-like adhesins in E. faecalis and other clinically-important Gram-positive species.

Original languageEnglish (US)
Pages (from-to)398-412
Number of pages15
JournalMolecular Microbiology
Volume103
Issue number3
DOIs
StatePublished - Feb 1 2017

Bibliographical note

Funding Information:
We thank Dr. Barbara Murray for providing strains used in the study and Maria Camilla Montealegre for help with strain and plasmid constructions. We thank members of our respective laboratories for helpful discussions. These studies were supported by NIH grants R01GM48746 (P.J.C) and R21AI105454 (P.J.C and G.M.D).

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