Small‐colony variants and phenotype switching of intracellular <i><scp>S</scp>taphylococcus aureus</i> in chronic rhinosinusitis

Tan, Neil; Cooksley, Clare; Roscioli, Eugene; Drilling, Amanda; Douglas, Richard; Wormald, Peter‐John; Vreugde, Sarah

doi:10.1111/all.12457

Cited by 40 publications

(44 citation statements)

References 34 publications

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“…However, the role of S. aureus SCVs in CRS is unclear. While some studies failed to detect SCVs in nasal lavage fluid and mucosal biopsy specimens from CRS patients (99, 100), other groups were able to cultivate intramucosal SCVs (S. aureus and other species) from respective sinonasal tissues of CRS patients (101,102).…”

Section: Infections Involving Skin Mucous Membranes Soft Tissues Amentioning

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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Section: Infections Involving Skin Mucous Membranes Soft Tissues Amentioning

confidence: 99%

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

2016

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“…A similar pattern was also observed in other studies. 10,20 The lack of association can be partly because S. aureus that resides intracellularly is known to switch to a SCV phenotype, 7 which has proven to be more difficult to culture using traditional agar techniques. These findings indicate that the result of conventional swab culture remains a poor predictor for the presence of S. aureus intracellularly.…”

Section: Discussionmentioning

confidence: 99%

“…SCVs were able to reversibly switch off their toxin production and did not induce a proinflammatory immune response to avoid detection by host cells. 7 This finding may explain the lack of inflammatory infiltrates in ICSA-positive sinonasal tissue. 6 This data suggests that S. aureus has the ability to exist within the host tissue for prolonged periods of time, evading the host's immune system, and potentially serving as a nidus of recurrent infections.…”

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confidence: 90%

“…Interestingly in this 3-year follow-up study they observed persistence of the same genotypes of S. aureus within these same patients, suggesting long-term viability of intracellular S. aureus. 4 A later study by Tan et al 7 showed the phenotypic transition of ICSA into a slow growing, metabolically quiescent small colony variant (SCV) form. SCVs were able to reversibly switch off their toxin production and did not induce a proinflammatory immune response to avoid detection by host cells.…”

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confidence: 99%

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Association of intracellular Staphylococcus aureus with prognosis in chronic rhinosinusitis

Drilling

Singhal

et al. 2016

Int Forum Allergy Rhinol

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“…Various genotypic factors (single nucleotide polymorphisms, mutations, and gene deletions) have now been identified to attempt to characterize S. aureus SCVs (10,[14][15][16]. S. aureus SCVs have now been clearly associated with different diseases, and importantly these include chronic infections, such as those in patients with cystic fibrosis, chronic rhinosinusitis, endocarditis, and chronic osteomyelitis (17)(18)(19) …”

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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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Small‐colony variants and phenotype switching of intracellular Staphylococcus aureus in chronic rhinosinusitis

Cited by 40 publications

References 34 publications

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

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

Association of intracellular Staphylococcus aureus with prognosis in chronic rhinosinusitis

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

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