The RNPP family of quorum-sensing proteins in Gram-positive bacteria

Rocha, Jorge; Aceves-Díez, Ángel E.; Guarneros, Gabriel; Torre, Mayra de la

doi:10.1007/s00253-010-2651-y

Cited by 126 publications

(132 citation statements)

References 48 publications

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“…Alternatively, some linear-peptide-based QS systems actively transport the autoinducers back into the cell where the peptide signal can interact directly with a cognate regulator to alter target gene expression. Such is the case for the PrgX system of E. facaelis (20) and the PlcR and NprR systems of Bacillus thuringiensis (20,24,25) (Fig. 2).…”

Section: Peptide-based Quorum Sensingmentioning

confidence: 80%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

676

556

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SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.

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Section: Peptide-based Quorum Sensingmentioning

confidence: 80%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

676

556

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“…Structure prediction algorithms have led to the proposal that Rgg proteins are members of the RNPP family (11,14,18). The carboxy-terminal regions of RNPP family proteins have predicted folds consistent with TPRs which mediate protein-protein or protein-peptide interactions (12,56). As observed for PrgX, PlcR, and Rgg proteins, no tetratricopeptide repeats (TPRs) could be predicted from the primary sequence of ElrR; however, the secondary structure of ElrR predicted by PSIPRED (57) reveals alpha-helices as reported for other Rgg-like proteins that align with the TPR helices of PlcR and PrgX (13).…”

Section: Resultsmentioning

confidence: 99%

“…The peptide-associated transcriptional regulators described to date belong to the RNPP superfamily, which includes the Rap (aspartyl phosphate phosphatase), NprR (neutral protease regulator), and PlcR (phospholipase C regulator) regulators of Bacillus species and PrgX of E. faecalis. All of these proteins contain tandem tetratricopeptide repeats (TPRs), which interact with cytoplasmic peptide signals (11,12). Recently, based on predicted structural similarities, Rgg family transcription factors have been proposed as candidates for members of the RNPP superfamily (13,14).…”

mentioning

confidence: 99%

Enterococcal Rgg-Like Regulator ElrR Activates Expression of the elrA Operon

et al. 2013

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The Enterococcus faecalis leucine-rich protein ElrA promotes virulence by stimulating bacterial persistence in macrophages and production of the interleukin-6 (IL-6) cytokine. The ElrA protein is encoded within an operon that is poorly expressed under laboratory conditions but induced in vivo. In this study, we identify ef2687 (renamed elrR), which encodes a member of the Rgg (regulator gene for glucosyltransferase) family of putative regulatory proteins. Using quantitative reverse transcription-PCR, translational lacZ fusions, and electrophoretic mobility shift assays, we demonstrate that ElrR positively regulates expression of elrA. These results correlate with the attenuated virulence of the ⌬elrR strain in a mouse peritonitis model. Virulence of simple and double elrR and elrA deletion mutants also suggests a remaining ElrR-independent expression of elrA in vivo and additional virulence-related genes controlled by ElrR.

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“…Based on the predicted structural homology of PrgX to the TraA proteins (see Fig. S2), it is likely that all three proteins are members of a growing family of peptide-modulated transcription factors of Gram-positive pathogens (RRNPP proteins) regulating diverse functions, including sporulation, biofilm formation, competent cell transformation, conjugation, and virulence (30)(31)(32)(33).…”

Section: Resultsmentioning

confidence: 99%

Antagonistic Donor Density Effect Conserved in Multiple Enterococcal Conjugative Plasmids

Bandyopadhyay

O’Brien

Frank

et al. 2016

Appl Environ Microbiol

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Enterococcus faecalis, a common causative agent of hospital-acquired infections, is resistant to many known antibiotics. Its ability to acquire and transfer resistance genes and virulence determinants through conjugative plasmids poses a serious concern for public health. In some cases, induction of transfer of E. faecalis plasmids results from peptide pheromones produced by plasmid-free recipient cells, which are sensed by the plasmid-bearing donor cells. These plasmids generally encode an inhibitory peptide that competes with the pheromone and suppresses self-induction of donors. We recently demonstrated that the inhibitor peptide encoded on plasmid pCF10 is part of a unique quorum-sensing system in which it functions as a "self-sensing signal," reducing the response to the pheromone in a density-dependent fashion. Based on the similarities between regulatory features controlling conjugation in pAD1 and pAM373 and those controlling conjugation in pCF10, we hypothesized that these plasmids are likely to exhibit similar quorum-sensing behaviors. Experimental findings indicate that for both pAD1 and pAM373, high donor densities indeed resulted in decreased induction of the conjugation operon and reduced conjugation frequencies. This effect was restored by the addition of exogenous inhibitor, confirming that the inhibitor serves as an indicator for donor density. Donor density also affects cross-species conjugative plasmid transfer. Based on our experimental results, we propose models for induction and shutdown of the conjugation operon in pAD1 and pAM373. IMPORTANCEEnterococcus faecalis is a leading cause of hospital-acquired infections. Its ability to transfer antibiotic resistance and virulence determinants by sharing its genetic material with other bacteria through direct cell-cell contact via conjugation poses a serious threat. Two antagonistic signaling peptides control the transfer of plasmids pAD1 and pAM373: a peptide pheromone produced by plasmid-free recipients triggers the conjugative transfer in plasmid-containing donors, and an inhibitor peptide encoded on the plasmid and produced by donor cells serves to modulate the donor response in accordance with the relative abundance of donors and recipients. We demonstrate that high donor density reduces the conjugation frequency of both of these plasmids, which is a consequence of increased inhibitor concentration in high-donor-density cultures. While most antibiotic strategies end up selecting resistant strains and disrupting the community balance, manipulating bacterial signaling mechanisms can serve as an alternate strategy to prevent the spread of antibiotic resistance. E nterococcus faecalis, a bacterium normally present in the human intestinal tract, is a major cause of health care-associated infections. Treatment of these infections has become increasingly difficult with the emergence of E. faecalis strains that are resistant to multiple antibiotics, such as macrolides, tetracyclines, amino glycosides, and glycopeptides, including vancomycin (...

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The RNPP family of quorum-sensing proteins in Gram-positive bacteria

Cited by 126 publications

References 48 publications

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Enterococcal Rgg-Like Regulator ElrR Activates Expression of the elrA Operon

Antagonistic Donor Density Effect Conserved in Multiple Enterococcal Conjugative Plasmids

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