The Agr Quorum-Sensing System Regulates Fibronectin Binding but Not Hemolysis in the Absence of a Functional Electron Transport Chain

Pader, Vera; James, Ellen; Painter, Kimberley L.; Wigneshweraraj, Sivaramesh; Edwards, Andrew M.

doi:10.1128/iai.02254-14

Cited by 30 publications

(25 citation statements)

References 68 publications

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“…Intracellular residency places S. aureus beyond the reach of immune surveillance and some antibiotics, while a lack of Agr-mediated toxin production results in a weak inflammatory response [94,95]. This is exemplified by the emergence of small colony variants, which are strongly associated with chronic and recurrent infections and lack the ability to produce cytolytic toxins due to diminished Agr activity and a disrupted electron transport chain [95,96].…”

Section: Community-associatedmentioning

confidence: 99%

What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

Painter¹,

Krishna²,

Wigneshweraraj³

et al. 2014

Trends in Microbiology

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150

139

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Section: Community-associatedmentioning

confidence: 99%

What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

Painter¹,

Krishna²,

Wigneshweraraj³

et al. 2014

Trends in Microbiology

Self Cite

150

139

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“…This phenomenon is not necessarily the result of a reduced concentration of the quorum-sensing peptide due to the reduced growth rate of the SCV (148). We (86) and Pader et al (167) showed that exogenous autoinducing peptide (AIP) is able to trigger RNAIII expresion in TD-SCVs (86) and in menadione-and hemin-dependent SCVs (167), thereby demonstrating that synthetic AIP is able to activate Agr in at least some SCVs. Based on cDNA libraries built from total RNA, which was collected from different growth phases of an S. aureus strain pair displaying both the normal and the SCV phenotype, phenotypespecific expression of non-protein-encoding RNAs (npcRNAs) was shown (168,169).…”

Section: Alterations In Electron Transport and Their Impact On Metabomentioning

confidence: 99%

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

2016

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SUMMARYSmall colony variants (SCVs) were first described more than 100 years ago forStaphylococcus aureusand various coagulase-negative staphylococci. Two decades ago, an association between chronic staphylococcal infections and the presence of SCVs was observed. Since then, many clinical studies and observations have been published which tie recurrent, persistent staphylococcal infections, including device-associated infections, bone and tissue infections, and airway infections of cystic fibrosis patients, to this special phenotype. By their intracellular lifestyle, SCVs exhibit so-called phenotypic (or functional) resistance beyond the classical resistance mechanisms, and they can often be retrieved from therapy-refractory courses of infection. In this review, the various clinical infections where SCVs can be expected and isolated, diagnostic procedures for optimized species confirmation, and the pathogenesis of SCVs, including defined underlying molecular mechanisms and the phenotype switch phenomenon, are presented. Moreover, relevant animal models and suggested treatment regimens, as well as the requirements for future research areas, are highlighted.

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“…These are all factors that interact or induce immune cell responses. Previous studies have shown that there is a quorum-sensing system, the accessory gene regulator (agr) system, in S. aureus, and this is central in the control of specific virulence factors (52)(53)(54). There have been studies that report mutations in the agr system and indeed mutations through the course of infection (54).…”

Section: Figmentioning

confidence: 99%

Prolonged Growth of a Clinical Staphylococcus aureus Strain Selects for a Stable Small-Colony-Variant Cell Type

et al. 2015

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dAn undetermined feature of Staphylococcus aureus pathogenesis is its persistence and then relapse of disease. This has been explained by its switch to alternative lifestyles, mainly as biofilm or small-colony variants (SCVs). Studying the native characteristics of SCVs has been problematic due to their reversion to the parental lifestyle. We have observed that for a number of S. aureus strains as they switch to an SCV lifestyle, there is the formation of an extracellular matrix. We focused our analysis on one strain, WCH-SK2. For bacterial survival in the host, the combination of low nutrients and the prolonged time frame forms a stress that selects for a specific cell type from the population. In this context, we used steady-state growth conditions with low nutrients and a controlled low growth rate for a prolonged time and with methylglyoxal. These conditions induced S. aureus WCH-SK2 into a stable SCV cell type; the cells did not revert after subculturing. Analysis revealed these cells possessed a metabolic and surface profile that was different from those of previously described SCVs or biofilm cells. The extracellular matrix was protein and extracellular DNA but not polysaccharide. The SCV cells induced expression of certain surface proteins (such as Ebh) and synthesis of lantibiotics while downregulating factors that stimulate the immune response (leucocidin, capsule, and carotenoid). Our data reveal cell heterogeneity within an S. aureus population and under conditions that resemble long-term survival in the host have identified a previously unnoticed S. aureus cell type with a distinctive metabolic and molecular profile. Staphylococcus aureus has an incredible ability to survive, either by adapting to environmental conditions or defending against exogenous stress. In part, this ability is provided by the breadth of lifestyles or modes of growth S. aureus can adopt. Key to an understanding of chronic, persistent, and relapsing S. aureus infections is determining the basis for their switch to quasi-dormant lifestyles. Across different bacterial species, these alternative lifestyles form a population known as persister cells (1). It has been proposed that while within their host, a subpopulation of S. aureus survives host-generated and therapeutic antimicrobial stresses by inducing biofilm growth on host tissue or by growing as smallcolony variants (SCVs). It is likely this is not an on-off switch, from planktonically growing cells to a biofilm or likewise to SCVs, but a continuum of cell types; the bacterial population will have the potential for a diverse range of lifestyles defined by different metabolic pathways and surface structures. In a multicellular biofilm, the metabolically quiescent bacterial community produces a highly protective extracellular polymeric substance (EPS). The EPS is variously composed of polysaccharides (mainly the ica operon-encoded polysaccharide intercellular adhesin [PIA]), extracellular DNA (eDNA), and protein, and its protection results in persistent bacterial infections (...

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The Agr Quorum-Sensing System Regulates Fibronectin Binding but Not Hemolysis in the Absence of a Functional Electron Transport Chain

Cited by 30 publications

References 68 publications

What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

Prolonged Growth of a Clinical Staphylococcus aureus Strain Selects for a Stable Small-Colony-Variant Cell Type

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