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PNAS 102 (43): 15617-15622

Copyright © 2005 by the National Academy of Sciences.

MICROBIOLOGY

A paracrine peptide sex pheromone also acts as an autocrine signal to induce plasmid transfer and virulence factor expression in vivo

Josephine R. Chandler *, Helmut Hirt *, {dagger}, and Gary M. Dunny *, {ddagger}

*Department of Microbiology, University of Minnesota, MMC 196, 420 Delaware Street SE, Minneapolis, MN 55455; and {dagger}Division of Biology, Kansas State University, 232 Ackert Hall, Manhattan, KS 66506

Edited by E. Peter Greenberg, University of Washington School of Medicine, Seattle, WA, and approved August 30, 2005

Received for publication June 30, 2005.

Abstract: The peptide pheromone cCF10 of Enterococcus faecalis is an intercellular signal for induction of conjugative transfer of plasmid pCF10 from donor cells to recipient cells. When a donor cell is exposed to recipient-produced cCF10, expression of the pCF10-encoded aggregation substance of pCF10 (Asc10) and other conjugation gene products is activated. Asc10 also increases enterococcal virulence in several models, and when donor cells are grown in animals or in plasma, Asc10 expression is induced by means of the cCF10-sensing machinery. Plasmid pCF10 carries two genes that function to prevent self-induction by endogenous cCF10 in donor cells. The membrane protein PrgY reduces endogenous pheromone activity in donor cells, and the inhibitor peptide iCF10 neutralizes the residual endogenous cCF10 that escapes PrgY. In the current study, we found that E. faecalis strains with allelic replacements abolishing active cCF10 production showed reduced ability to acquire pCF10 by conjugation; prgY-null mutations had no phenotype in the cCF10-negative strains. We observed that expression of the mRNA for iCF10 was reduced in this background and that these mutations also blocked plasma induction of Asc10 expression. These findings support a model in which plasma induction in wild-type donors results from iCF10 inactivation by a plasma component, causing disruption of a precisely maintained balance of iCF10 to cCF10 activity and allowing subsequent induction by endogenous cCF10. Although cCF10 has traditionally been viewed as an intercellular signal, these results show that pCF10 has also adapted cCF10 as an autocrine signal that activates expression of virulence and conjugation functions.

Key Words: cell–cell signaling • Enterococcus • horizontal gene transfer • pCF10

Author contributions: J.R.C., H.H., and G.M.D. designed research; J.R.C. and H.H. performed research; J.R.C., H.H., and G.M.D. analyzed data; and J.R.C. and G.M.D. wrote the paper.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviation: Asc10, aggregation substance of pCF10.

{ddagger} To whom correspondence should be addressed. E-mail: gary-d{at}biosci.cbs.umn.edu.

© 2005 by The National Academy of Sciences of the USA

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