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

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. © 2014 brooks,jefferson.