| Title: | A paracrine peptide sex pheromone also acts as an autocrine signal to induce plasmid transfer and virulence factor expression in vivo |
| Author(s): | Chandler JR; Hirt H; Dunny GM; |
| Address: | "Department of Microbiology, University of Minnesota, MMC 196, 420 Delaware Street SE, Minneapolis, MN 55455, USA" |
| ISSN/ISBN: | 0027-8424 (Print) 1091-6490 (Electronic) 0027-8424 (Linking) |
| 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" |
| Keywords: | "Amino Acid Sequence *Conjugation, Genetic Enterococcus faecalis/*genetics *Gene Transfer, Horizontal Humans Molecular Sequence Data Oligopeptides/*physiology Pheromones/*physiology *Plasmids Serum Albumin/metabolism Signal Transduction Virulence Factors/*;" |
| Notes: | "MedlineChandler, Josephine R Hirt, Helmut Dunny, Gary M eng T32 DE007288/DE/NIDCR NIH HHS/ HL 51987/HL/NHLBI NIH HHS/ GM 49530/GM/NIGMS NIH HHS/ T32 DE 07288/DE/NIDCR NIH HHS/ R01 GM049530/GM/NIGMS NIH HHS/ R01 HL051987/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. 2005/10/15 Proc Natl Acad Sci U S A. 2005 Oct 25; 102(43):15617-22. doi: 10.1073/pnas.0505545102. Epub 2005 Oct 13" |
