The Presence of
            <i>icaADBC</i>
            Is Detrimental to the Colonization of Human Skin by
            <i>Staphylococcus epidermidis</i>

Rogers, Kathie L.; Rupp, Mark E.; Fey, Paul D.

doi:10.1128/aem.01017-08

Cited by 35 publications

(24 citation statements)

References 19 publications

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“…Therefore, despite the metabolic cost, selection pressures that favor the PIA/PNAG-negative phase variants are likely less pronounced in vivo. However, skin colonization and ocular infections appear to favor the PIA/PNAG-negative phenotype in S. epidermidis and ica -negative clinical isolates of S. aureus have been detected as well [23], [24], [28]. Furthermore, as PCR amplification of the ica genes is often used to demonstrate the capacity to produce PIA/PNAG [29], [30], our finding that a 4-nt indel mutation can shut off PIA/PNAG production suggests that PIA/PNAG negative clinical isolates may be more prevalent than previously appreciated.…”

Section: Discussionmentioning

confidence: 99%

Phase Variation of Poly-N-Acetylglucosamine Expression in Staphylococcus aureus

Brooks

Jefferson

2014

PLoS Pathog

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Polysaccharide intercellular adhesin (PIA), also known as poly-N-acetyl-β-(1–6)-glucosamine (PIA/PNAG) is an important component of Staphylococcus aureus biofilms and also contributes to resistance to phagocytosis. The proteins IcaA, IcaD, IcaB, and IcaC are encoded within the intercellular adhesin (ica) operon and synthesize PIA/PNAG. We discovered a mechanism of phase variation in PIA/PNAG expression that appears to involve slipped-strand mispairing. The process is reversible and RecA-independent, and involves the expansion and contraction of a simple tetranucleotide tandem repeat within icaC. Inactivation of IcaC results in a PIA/PNAG-negative phenotype. A PIA/PNAG-hyperproducing strain gained a fitness advantage in vitro following the icaC mutation and loss of PIA/PNAG production. The mutation was also detected in two clinical isolates, suggesting that under certain conditions, loss of PIA/PNAG production may be advantageous during infection. There was also a survival advantage for an icaC-negative strain harboring intact icaADB genes relative to an isogenic icaADBC deletion mutant. Together, these results suggest that inactivation of icaC is a mode of phase variation for PIA/PNAG expression, that high-level production of PIA/PNAG carries a fitness cost, and that icaADB may contribute to bacterial fitness, by an unknown mechanism, in the absence of an intact icaC gene and PIA/PNAG production.

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Section: Discussionmentioning

confidence: 99%

Phase Variation of Poly-N-Acetylglucosamine Expression in Staphylococcus aureus

Brooks

Jefferson

2014

PLoS Pathog

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“…Carriage of the ica locus by S. epidermidis implicates a fitness cost, and isolates lacking ica genes are able to outcompete strains carrying this locus (38). Moreover, no association has been demonstrated between PIA expression and colonization, whereas Aap, in addition to its role in biofilm accumulation, has been also demonstrated to be an important surface adhesin for skin colonization by promoting adhesion to corneocytes (39).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Ocular Methicillin-Resistant Staphylococcus epidermidis Isolates Belonging Predominantly to Clonal Complex 2 Subcluster II

2014

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Staphylococcus epidermidis is an abundant member of the microbiota of the human skin and wet mucosa, which is commonly associated with sight-threatening infections in eyes with predisposing factors. Ocular S. epidermidis has become notorious because of its capability to form biofilms on different ocular devices and due to the evolving rates of antimicrobial resistance. In this study, the molecular epidemiology of 30 ocular methicillin-resistant S. epidermidis (MRSE) isolates was assessed using multilocus sequence typing (MLST). Antimicrobial resistance, accessory gene-regulator and staphylococcal cassette chromosome mec (SCCmec) types, biofilm formation, and the occurrence of biofilm-associated genes were correlated with MLST clonal complexes. Sequence types (STs) frequently found in the hospital setting were rarely found in our collection. Overall, 12 different STs were detected with a predominance of ST59 (30%), ST5 and ST6 (13.3% each). Most of the isolates (93.3%) belonged to the clonal complex 2 (CC2) and grouped mainly within subcluster CC2-II (92.9%). Isolates grouped within this subcluster were frequently biofilm producers (92.3%) with a higher occurrence of the aap (84.5%) and bhp (46.1%) genes compared to icaA (19.2%). SCCmec type IV (53.8%) was predominant within CC2-II strains, while 38.4% were nontypeable. In addition, CC2-II strains were frequently multidrug resistant (80.7%) and demonstrated to be particularly resistant to ciprofloxacin (80.8%), ofloxacin (77%), azithromycin (61.5%), and gentamicin (57.7%). Our findings demonstrate the predominance of a particular MRSE cluster causing ocular infections, which was associated with high rates of antimicrobial resistance and particularly the carriage of biofilm-related genes coding for proteinaceous factors implicated in biofilm accumulation.

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“…The ica operon encodes enzymes that are involved in the production of polysaccharide intercellular adhesion (PIA), which mediates the intercellular adherence of bacteria and the accumulation of multilayer biofilms (8). Nevertheless, ica is not ubiquitously distributed in S. epidermidis (5,8,21), and icanegative isolates also produce biofilm (19). Furthermore, the impact of exogenous substances, such as antibiotics, on bacterial biofilm formation has also drawn much attention (3,6,7,11,12,23), although the numbers of studies performed with S. epidermidis are still limited.…”

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confidence: 99%

Enhancement of Biofilm Formation by Subinhibitory Concentrations of Macrolides in icaADBC- Positive and -Negative Clinical Isolates of Staphylococcus epidermidis

Wang

Sun

Liu

et al. 2010

Antimicrob Agents Chemother

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Biofilm formation in Staphylococcus epidermidis is mediated by icaADBC-dependent and -independent pathways. Subinhibitory concentrations of erythromycin, azithromycin, and clarithromycin enhanced, in a dosedependent manner, the level of biofilm formation by 20% (21/105 isolates) by macrolide-resistant ica-positive and -negative isolates tested in vitro. The presence of ica, however, apparently produced an enhanced effect on biofilm formation. The levels of expression of the biofilm-related genes icaA, atlE, fruA, pyrR, sarA, and sigB were increased in response to erythromycin. The results likely underscore the potential clinical relevance of macrolide-induced biofilm growth.Staphylococcus epidermidis, a key nosocomial pathogen, is frequently associated with the use of indwelling medical devices and forms biofilms (9). The latter is mediated by icaADBC-dependent and -independent pathways (8, 17). The ica operon encodes enzymes that are involved in the production of polysaccharide intercellular adhesion (PIA), which mediates the intercellular adherence of bacteria and the accumulation of multilayer biofilms (8). Nevertheless, ica is not ubiquitously distributed in S. epidermidis (5,8,21), and icanegative isolates also produce biofilm (19). Furthermore, the impact of exogenous substances, such as antibiotics, on bacterial biofilm formation has also drawn much attention (3,6,7,11,12,23), although the numbers of studies performed with S. epidermidis are still limited. Macrolides, which include erythromycin (ERY), clarithromycin (CLR), and azithromycin (AZM), are among the most frequently used antibiotics in clinical settings. A subinhibitory concentration of ERY induced ica expression (20), suggesting a possible role of macrolides in biofilm formation, but the eradication of the slimelike glycocalyx matrix and, thus, the eradication of antibiofilm activity by a subinhibitory concentration of CLR in a CLRresistant isolate of S. epidermidis (whose ica status was unknown) were also reported (24). The study described here was thus carried out to investigate the role of macrolides in biofilm formation and its relation to the ica status of S. epidermidis. We show that a large number of clinical isolates of S. epidermidis had significantly enhanced levels of biofilm formation after treatment with macrolides and that biofilm formation was independent of the ica status.Of 121 S. epidermidis strains isolated from our hospital during the period from August 2007 to December 2008, 105 isolates (87%) were resistant to ERY (MIC Ͼ 8 g/ml), with most of the isolates being highly resistant to ERY, CLR, and AZM (MICs Ն 128 g/ml), although they were susceptible to vancomycin (VAN; MICs ϭ 1 to 2 g/ml). By using a microtiter plate assay for biofilm formation (1) with cells grown in tryptic soy broth medium, ERY at 1/4ϫ MIC (i.e., over the range of 4 to 32 g/ml) was found to significantly enhance the level of biofilm formation in 20% (21/105) of the ERY-resistant isolates (Tables 1 and 2). Two other macrolides, AZM and CLR, also caused a s...

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The Presence of icaADBC Is Detrimental to the Colonization of Human Skin by Staphylococcus epidermidis

Cited by 35 publications

References 19 publications

Phase Variation of Poly-N-Acetylglucosamine Expression in Staphylococcus aureus

Phase Variation of Poly-N-Acetylglucosamine Expression in Staphylococcus aureus

Characterization of Ocular Methicillin-Resistant Staphylococcus epidermidis Isolates Belonging Predominantly to Clonal Complex 2 Subcluster II

Enhancement of Biofilm Formation by Subinhibitory Concentrations of Macrolides in icaADBC- Positive and -Negative Clinical Isolates of Staphylococcus epidermidis

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