Article

Peptide Signaling in the Staphylococci

Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Chemical Reviews (Impact Factor: 46.57). 01/2011; 111(1):117-51. DOI: 10.1021/cr100370n
Source: PubMed

ABSTRACT

Gram-negative and Gram-positive bacteria have evolved elaborate machinery to biosynthesize and respond to diverse small-molecule signals. One of the more intriguing classes of peptide signals are the cyclic lactones and thiolactones. The first of these cyclic peptide signals was discovered in Staphylococcus aureus. S. aureus is a remarkable bacterial pathogen that is known for causing a diverse array of acute and chronic infections. This pathogen secretes an impressive arsenal of virulence determinants to combat the host, including pore-forming toxins, tissue degrading enzymes, and immune evasion factors. RNAIII is the agr-induced regulatory RNA that is the primary effector of the system. RNAIII is capable of regulating gene expression at the post-transcriptional level by affecting mRNA stability and promoting or inhibiting mRNA translation. S. aureus AgrC is part of a growing family of peptide inducible histidine protein kinases (HPK) that regulate various group behaviors in Gram-positive bacteria.

Download full-text

Full-text

Available from: Caralyn E Flack, May 22, 2014
  • Source
    • "The agr is a QS system that acts upon a diverse range of genes in S. aureus. Activation of this system may result in either the induction or repression of expression of various genes, which may occur at the level of transcription, mRNA stabilization and translation initiation [20]. In the case of epidermin, agr-deficient cells are unable to express an active EpiP, which precludes epidermin maturation, resulting in an inactive bacteriocin [21]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aureocin A70 is a four-component bacteriocin produced by Staphylococcus aureus A70. Its locus encompasses three transcriptional units coding for: (i) structural peptides (aurABCD), (ii) anABC transporter (aurT) and (iii) the dedicated immunity protein and a putative transcriptional regulator (aurRI). The data provided here showed that AurR is an HTH-containing protein that reduces aureocin A70 production on solid medium, but not in broth. AurR seems to work similarly to LtnR and CylR2, repressors of lantibiotics lacticin 3147 and cytolysin, respectively. At least two other factors play a role in aureocin A70 production: (i) the alternative σ(B) factor, as σ(B)-defective cells produce more bacteriocin than the restored σ(B+) cells, and (ii) the ϕ11 regulator cI, since a lysogenic strain for ϕ11 exhibited a significant reduction in aureocin A70 production on solid medium when compared with the non-lysogenic isogenic strain. Full aeration and ROS generation abolished the effect of the phage regulators on aureocin A70 production. Interestingly, the ϕ11 regulator cI seems to cooperate with AurR to abolish aureocin A70 production. This study therefore represents the first report showing that phage regulators may play a role in regulation of bacteriocin production.
    Full-text · Article · Nov 2015 · Research in Microbiology
  • Source
    • "A possible explanation for this phenomenon may be the effect of physical stimulation on gene expression. Nevertheless, previous studies have indicated that the agr system works in a cell-density dependent manner (Thoendel et al. 2011). Thus, another possibility that can be inferred from our data may be a decrease of bacterial density. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Negative pressure wound therapy (NPWT) has gained popularity in the management of contaminated wounds as an effective physical therapy, although its influence on the bacteria in the wounds remains unclear. In this study, we attempted to explore the effect of negative pressure conditions on Staphylococcus aureus, the most frequently isolated pathogen during wound infection. S. aureus was cultured in Luria-Bertani medium at subatmospheric pressure of -125 mmHg for 24 h, with the bacteria grown at ambient pressure as the control. The application of negative pressure was found to slow down the growth rate and inhibit biofilm development of S. aureus, which was confirmed by static biofilm assays. Furthermore, decreases in the total amount of virulence factors and biofilm components were observed, including α-hemolysin, extracellular adherence protein, polysaccharide intercellular adhesin and extracellular DNA. With quantitative RT-PCR analysis, we also revealed a significant inhibition in the transcription of virulence and regulatory genes related to wound infections and bacterial biofilms. Together, these findings indicated that negative pressure could inhibit the growth, virulence and biofilm formation of S. aureus. A topical subatmospheric pressure condition, such as NPWT, may be a potential antivirulence and antibiofilm strategy in the field of wound care.
    Full-text · Article · Aug 2015 · Antonie van Leeuwenhoek
  • Source
    • "We therefore refer to AgrC-I 1–200 as the sensor domain and AgrC-I 201–221 as the TMH-DHp linker region. As described previously, the DHp and CA subdomains are defined by residues AgrC-I 222–290 and AgrC-I 293–430 , respectively, with a very short intersubdomain linker between them (Thoendel et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Staphylococcus aureus virulence is regulated when secreted autoinducing peptides (AIPs) are recognized by a membrane-bound receptor histidine kinase (RHK), AgrC. Some AIPs are agonists of virulence gene expression, while others are antagonists. It is unclear how AIP binding regulates AgrC activity. Here, we reconstitute an AgrC family member, AgrC-I, using nanometer-scale lipid bilayer discs. We show that AgrC-I requires membranes rich in anionic lipids to function. The agonist, AIP-I, binds AgrC-I noncooperatively in a 2:2 stoichiometry, while an antagonist ligand, AIP-II, functions as an inverse agonist of the kinase activity. We also demonstrate the kinase and sensor domains in AgrC are connected by a helical linker whose conformational state exercises rheostat-like control over the kinase activity. Binding of agonist or inverse-agonist peptides results in twisting of the linker in different directions. These two observations provide a view of the molecular motions triggered by ligand binding in an intact membrane-bound RHK.
    Full-text · Article · Mar 2014 · Molecular cell
Show more