Phase variation of poly-N-acetylglucosamine expression in Staphylococcus aureus.
Phase variation of poly-N-acetylglucosamine expression in Staphylococcus aureus.
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DOI：
10.1371/journal.ppat.1004292
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发表时间：
2014-07
期刊：
影响因子：
6.7
通讯作者：
Jefferson KK
中科院分区：
文献类型：
--
作者：
Brooks JL;Jefferson KK
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. Staphylococcal polysaccharide intercellular adhesin (PIA), also known as β-1-6-linked N-acetylglucosamine (PNAG) plays a role in immune evasion and biofilm formation. Evidence suggests that under certain circumstances PIA/PNAG production is beneficial, whereas at times, it may be advantageous for the bacteria to turn production off. In S. epidermidis, PIA/PNAG can be switched off when an insertion sequence recombines into the intercellular adhesin locus (ica). In this study, we have found a short tandem repeat sequence in the ica locus of S. aureus that can undergo expansion and contraction. The addition or subtraction of non-multiples of three of this repeat shifts the reading frame of the icaC gene, resulting in the complete loss of PIA/PNAG production. We hypothesize that certain conditions that make the PIA/PNAG-negative phenotype advantageous during infection, such as the development of an effective immune response to PIA/PNAG on the bacterial surface, would select for repeat mutants. In support of this hypothesis, we found clinical isolates with expansion and deletion of the repeat. These findings reveal a new on-off switch for the expression of PIA/PNAG.
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