title: agr function in clinical Staphylococcus aureus isolates.
abstract: The accessory gene regulator (agr) of Staphylococcus aureus is a global regulator of the staphylococcal virulon, which includes secreted virulence factors and surface proteins. The agr locus is important for virulence in a variety of animal models of infection, and has been assumed by inference to have a major role in human infection. Although most human clinical S. aureus isolates are agr(+), there have been several reports of agr-defective mutants isolated from infected patients. Since it is well known that the agr locus is genetically labile in vitro, we have addressed the question of whether the reported agr-defective mutants were involved in the infection or could have arisen during post-isolation handling. We obtained a series of new staphylococcal isolates from local clinical infections and handled these with special care to avoid post-isolation mutations. Among these isolates, we found a number of strains with non-haemolytic phenotypes owing to mutations in the agr locus, and others with mutations elsewhere. We have also obtained isolates in which the population was continuously heterogeneous with respect to agr functionality, with agr(+) and agr(-) variants having otherwise indistinguishable chromosomal backgrounds. This finding suggested that the agr(-) variants arose by mutation during the course of the infection. Our results indicate that while most clinical isolates are haemolytic and agr(+), non-haemolytic and agr(-) strains are found in S. aureus infections, and that agr(+) and agr(-) variants may have a cooperative interaction in certain types of infections.
authors.affiliation: Molecular Pathogenesis Program and Department of Microbiology and Medicine, Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, NY 10016, USA.
authors.forename: Katrina E
authors.initials: KE
authors.lastname: Traber
authors.affiliation: Molecular Pathogenesis Program and Department of Microbiology and Medicine, Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, NY 10016, USA.
authors.forename: Elsie
authors.initials: E
authors.lastname: Lee
authors.affiliation: New York University School of Medicine, NY 10016, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Benson
authors.affiliation: Trinity College, University of Dublin, Dublin 2, Ireland.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Corrigan
authors.affiliation: New York University School of Medicine, NY 10016, USA.
authors.forename: Mariela
authors.initials: M
authors.lastname: Cantera
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, NY 10016, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Shopsin
authors.affiliation: Molecular Pathogenesis Program and Department of Microbiology and Medicine, Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, NY 10016, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Novick
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015373:Bacterial Typing Techniques; D001483:Base Sequence; D005838:Genotype; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D006460:Hemolysin Proteins; D015534:Trans-Activators