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


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.

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Available from: Caralyn E Flack, May 22, 2014
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    • "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. "
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    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.
    Antonie van Leeuwenhoek 08/2015; 108(4). DOI:10.1007/s10482-015-0545-9 · 1.81 Impact Factor
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    • "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). "
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    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.
    Molecular cell 03/2014; 53(6):929-40. DOI:10.1016/j.molcel.2014.02.029 · 14.02 Impact Factor
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    • "HA-MRSA strains often do not express agr RNAIII (Rudkin et al., 2012), whereas RNAIII is very highly expressed in CA-MRSA strains of the USA300 lineage (Cheung et al., 2011). As agr is the master regulator of gene expression in S. aureus, differences in RNAIII production are responsible for pleiotropic effects on gene expression (Novick, 2003; Thoendel et al., 2011). Biofilm formation by HA-MRSA strains has been studied in detail (O'Neill et al., 2007, 2008; Pozzi et al., 2012; Geoghegan et al., 2013), but much less is known about how other clinical strains (in particular CA-MRSA isolates) form biofilm. USA300 strain LAC forms biofilm in vitro and in vivo (Lauderdale et al., 2009, 2010; Thurlow et al., 2011; Zielinska et al., 2012), and recent studies have focused on elucidating the composition of the biofilm matrix. "
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    ABSTRACT: Community associated methicillin resistant Staphylococcus aureus of the USA300 lineage is emerging as an important cause of medical device-related infection. However few factors required for biofilm accumulation by USA300 strains have been identified and the processes involved are poorly understood. Here we identify S. aureus proteins required for the USA300 isolate LAC to form biofilm. A mutant with a deletion of the fnbA and fnbB genes did not express the fibronectin binding proteins FnBPA and FnBPB and lacked the ability to adhere to fibronectin or to form biofilm. Biofilm formation by the mutant LAC∆fnbAfnbB could be restored by expression of FnBPA or FnBPB from a plasmid demonstrating that both of these proteins can mediate biofilm formation when expressed by LAC. Expression of FnBPA and FnBPB increased bacterial aggregation suggesting that fibronectin binding proteins can promote the accumulation phase of biofilm. Loss of fibronectin binding proteins reduced the initial adherence of bacteria indicating that these proteins are also involved in primary attachment. In summary, these findings improve our understanding of biofilm formation by the USA300 strain LAC by demonstrating that the fibronectin binding proteins are required.This article is protected by copyright. All rights reserved.
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