title: Phase variation of poly-N-acetylglucosamine expression in Staphylococcus aureus.
abstract: 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.
authors: Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America.
authors: Jamie L
authors: JL
authors: Brooks
authors: Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America.
authors: Kimberly K
authors: KK
authors: Jefferson
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D018441:Biofilms; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009876:Operon; D044367:Phase Transition; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013203:Staphylococcal Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000254:growth & development / Q000302:isolation & purification* / Q000378:metabolism; D020080:Tandem Repeat Sequences; D014407:Tumor Cells, Cultured; D047071:beta-Glucans / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; D012333:RNA, Messenger; D047071:beta-Glucans; C113831:poly-N-acetyl glucosamine; C505465:poly-N-acetyl-1-6-glucosamine; C113579:polysaccharide intercellular adhesin; D000117:Acetylglucosamine