Enterococcal sex pheromones: Evolutionary pathways to complex, two-signal systems

Gary M. Dunny, Ronnie Per Arne Berntsson

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50 Scopus citations


Gram-positive bacteria carry out intercellular communication using secreted peptides. Important examples of this type of communication are the enterococcal sex pheromone systems, in which the transfer of conjugative plasmids is controlled by intercellular signaling among populations of donors and recipients. This review focuses on the pheromone response system of the conjugative plasmid pCF10. The peptide pheromones regulating pCF10 transfer act by modulating the ability of the PrgX transcription factor to repress the transcription of an operon encoding conjugation functions. Many Gram-positive bacteria regulate important processes, including the production of virulence factors, biofilm formation, sporulation, and genetic exchange using peptide-mediated signaling systems. The key master regulators of these systems comprise the RRNPP (RggRap/NprR/ PlcR/PrgX) family of intracellular peptide receptors; these regulators show conserved structures. While many RRNPP systems include a core module of two linked genes encoding the regulatory protein and its cognate signaling peptide, the enterococcal sex pheromone plasmids have evolved to a complex system that also recognizes a second host-encoded signaling peptide. Additional regulatory genes not found in most RRNPP systems also modulate signal production and signal import in the enterococcal pheromone plasmids. This review summarizes several structural studies that cumulatively demonstrate that the ability of three pCF10 regulatory proteins to recognize the same 7-amino-acid pheromone peptide arose by convergent evolution of unrelated proteins from different families. We also focus on the selective pressures and structure/function constraints that have driven the evolution of pCF10 from a simple, single-peptide system resembling current RRNPPs in other bacteria to the current complex inducible plasmid transfer system.

Original languageEnglish (US)
Pages (from-to)1556-1562
Number of pages7
JournalJournal of bacteriology
Issue number11
StatePublished - Jun 1 2016

Bibliographical note

Funding Information:
The research for this review was supported by U.S. PHS grant GM49530 to G.M.D. and by the Kempe Foundations grant JCK-1524 to R.P.-A.B. This work, including the efforts of Gary M. Dunny, was funded by HHS | National Institutes of Health (NIH) (GM49530). This work, including the efforts of Ronnie Per-Arne Berntsson, was funded by Kempestiftelserna (Kempe Foundations) (JCK-1524).

Publisher Copyright:
© 2016, American Society for Microbiology.


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