title: A point mutation in the agr locus rather than expression of the Panton-Valentine leukocidin caused previously reported phenotypes in Staphylococcus aureus pneumonia and gene regulation.
abstract: sThe role of Panton-Valentine leukocidin (PVL) in Staphylococcus aureus pathogenesis is controversial. Here, we show that an unintended point mutation in the agr P2 promoter of S. aureus caused the phenotypes in gene regulation and murine pneumonia attributed to PVL by earlier investigators. In agreement with other studies that failed to detect similar effects of PVL using community-associated methicillin-resistant S. aureus strains, we found no significant effect of PVL on gene expression or pathogenesis after we repaired the mutation. These findings provide further evidence that PVL does not have a major impact on S. aureus pathogenesis. Moreover, our results demonstrate that a single nucleotide polymorphism in an intergenic region can dramatically affect bacterial physiology and virulence. Finally, our work emphasizes the need to frequently evaluate the integrity of the S. aureus agr locus.
authors: Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Amer E
authors: AE
authors: Villaruz
authors: Juliane
authors: J
authors: Bubeck Wardenburg
authors: Burhan A
authors: BA
authors: Khan
authors: Adeline R
authors: AR
authors: Whitney
authors: Daniel E
authors: DE
authors: Sturdevant
authors: Donald J
authors: DJ
authors: Gardner
authors: Frank R
authors: FR
authors: DeLeo
authors: Michael
authors: M
authors: Otto
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis*; D001427:Bacterial Toxins / Q000096:biosynthesis*; D001483:Base Sequence; D001835:Body Weight; D017714:Community-Acquired Infections / Q000382:microbiology; D005098:Exotoxins / Q000096:biosynthesis*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007956:Leukocidins / Q000096:biosynthesis*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D011023:Pneumonia, Staphylococcal / Q000382:microbiology*; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000096:biosynthesis*; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D015534:Trans-Activators; D037521:Virulence Factors