Cell-Associated Pheromone Peptide (cCF10) Production and Pheromone Inhibition in
            <i>Enterococcus faecalis</i>

Buttaro, Bettina A.; Antiporta, Michelle H.; Dunny, Gary M.

doi:10.1128/jb.182.17.4926-4933.2000

Cited by 58 publications

(53 citation statements)

References 41 publications

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“…Because donor cells become competent for conjugation only when Q L and longer prgQ transcripts are expressed (13)(14)(15), we examined the dynamics of turning ON and OFF of conjugation by using quantitative RT-PCR (qRT-PCR, Table S1) to measure levels of these transcripts following exposure to various levels of C. Q L and transcripts of three downstream conjugation genes, prgB, pcfC, and pcfG ( Fig. 1), showed similar rapid increases to maximum levels within 15-30 min of exposure of pCF10-containing donor cells to various amounts of C (Fig.…”

Section: Resultsmentioning

confidence: 99%

Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer

Chatterjee

Cook

Shu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Conjugation is one of the most common ways bacteria acquire antibiotic resistance, contributing to the emergence of multidrugresistant "superbugs." Bacteria of the genus Enterococcus faecalis are highly antibiotic-resistant nosocomial pathogens that use the mechanism of conjugation to spread antibiotic resistance between resistance-bearing donor cells and resistance-deficient recipient cells. Here, we report a unique quorum sensing-based communication system that uses two antagonistic signaling molecules to regulate conjugative transfer of tetracycline-resistance plasmid pCF10 in E. faecalis. A "mate-sensing" peptide sex pheromone produced by recipient cells is detected by donor cells to induce conjugative genetic transfer. Using mathematical modeling and experimentation, we show that a second antagonistic "self-sensing" signaling peptide, previously known to suppress self-induction of donor cells, also serves as a classic quorum-sensing signal for donors that functions to reduce antibiotic-resistance transfer at high donor density. This unique form of quorum sensing may provide a means of limiting the spread of the plasmid and present opportunities to control antibiotic-resistance transfer through manipulation of intercellular signaling, with implications in the clinical setting.

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Section: Resultsmentioning

confidence: 99%

Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer

Chatterjee

Cook

Shu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Cells unable to produce iCF10 show a slight increase in expression of Asc10, as would be expected with autoinduction by cCF10 (4). In addition, the cell wall of E. faecalis contains a considerable amount of cCF10 activity (5). The membrane protein PrgY was recently shown to reduce the level of cCF10 activity in the cell wall (5), therefore preventing induction by cell wall-associated pheromone.…”

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confidence: 90%

In Vivo Induction of Virulence and Antibiotic Resistance Transfer in Enterococcus faecalis Mediated by the Sex Pheromone-Sensing System of pCF10

2002

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Enterococcus faecalis has become one of the most notable nosocomial pathogens in the last decade. Aggregation substance (AS) on the sex pheromone plasmids of E. faecalis has been implicated as a virulence factor in several model systems. We investigated the AS-encoding plasmid pCF10 for its ability to increase virulence in a rabbit endocarditis model. Cells containing pCF10 increased the virulence in the model significantly, as assessed by an increase in aortic valve vegetation size. The results confirmed in vivo induction of the normally tightly controlled AS. In addition to the expression of AS when E. faecalis cells were in contact with plasma, plasmid transfer of the tetracycline resistance-carrying plasmid was also activated in vitro and in vivo. In vivo, plasmid transfer reached remarkable frequencies of 8 ؋ 10 ؊2 to 9 ؋ 10 ؊2 . These values are comparable to the highest frequencies ever observed in vitro. Cells harboring pCF10 had a significant survival advantage over plasmid-free cells indicated by pCF10 present in two-thirds of the recipient population. Plasma induction was dependent on the presence of the plasmid-encoded PrgZ protein, indicating the requirement of the pheromonesensing system in the induction process. The data suggested that the mechanism of in vivo induction may involve interference of plasma with the normal function of the pheromone peptide and its inhibitor. Aggregation substance (AS) is a 137-kDa surface protein encoded on sex pheromone plasmids of Enterococcus faecalis.This protein mediates strong binding between E. faecalis cells as manifested by the formation of visible cell aggregates preceding the conjugative transfer of a sex pheromone plasmid (14). The plasmid transfer response is initiated by 7-to 8-amino-acid-long hydrophobic peptides secreted by potential recipient cells (16,32). These peptides are part of signal sequences of chromosomally encoded lipoproteins (10) and lead to induction of AS expression.Asc10, the AS of the sex pheromone plasmid pCF10 (encoding tetracycline resistance) (17), is induced by the 7-aminoacid peptide cCF10 (32) encoded by the ccfA gene. The donor cell binds the peptide (37), employing a specific plasmid-encoded receptor, PrgZ, an OppA homologue (Fig. 1). The peptide is then transported into the cell via the oligopeptide permease system (29), leading to the expression of AS and subsequent plasmid transfer. Since expression of AS and the other plasmid transfer machinery is presumably a very energyconsuming process, it is not surprising that expression of AS is tightly regulated. This ensures that the nonmotile enterococcal cells expressing transfer functions are in close proximity for cell contact to occur between mating partners. pCF10 donor cells are faced with the dilemma that they secrete unaltered amounts of cCF10 (33), necessitating a complex scheme to prevent autoinduction by their own pheromones. A schematic overview of the events controlling AS expression is given in Fig. 1. Secreted cCF10 may accumulate to approximately 8 pg/ml (33). To...

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“…A putative integral membrane protease called Eep is involved in processing the CcfA-signal peptide to active cCF10 pheromone (4). After processing in the membrane, mature cCF10 can be found both in the culture medium and associated with the cell wall fraction of recipient cells (5). The pheromone response in donor cells entails binding of the cCF10 peptide by the pCF10-encoded PrgZ protein, followed by import into the cytoplasm by a chromosomal oligopeptide permease ABC transporter (6).…”

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confidence: 99%

“…PrgY is a membrane protein that is essential to block self-induction by pCF10-carrying donors. PrgY has been shown to reduce the amount of both excreted and cell-associated pheromone in donor cells, possibly by binding or degrading cCF10 as it is released from the outer surface of the membrane (5,11). Control of the residual donor pheromone activity that is not blocked by PrgY is mediated by an inhibitor peptide, iCF10.…”

mentioning

confidence: 99%

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

Chandler

Hirt

Dunny

2005

Proc. Natl. Acad. Sci. U.S.A.

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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.cell-cell signaling ͉ Enterococcus ͉ horizontal gene transfer ͉ pCF10

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Cell-Associated Pheromone Peptide (cCF10) Production and Pheromone Inhibition in Enterococcus faecalis

Cited by 58 publications

References 41 publications

Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer

Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer

In Vivo Induction of Virulence and Antibiotic Resistance Transfer in Enterococcus faecalis Mediated by the Sex Pheromone-Sensing System of pCF10

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

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