title: Mechanism of Gene Regulation by a Staphylococcus aureus Toxin.
abstract: The virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently large amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves. However, mechanisms by which toxins regulate gene expression have remained poorly understood. We show here that the staphylococcal phenol-soluble modulin (PSM) toxins have gene regulatory functions that, in particular, include inducing expression of their own transport system by direct interference with a GntR-type repressor protein. This capacity was most pronounced in PSMs with low cytolytic capacity, demonstrating functional specification among closely related members of that toxin family during evolution. Our study presents a molecular mechanism of gene regulation by a bacterial toxin that adapts bacterial physiology to enhanced toxin production.
  
  
  
  Toxins play a major role in many bacterial diseases. When toxins are produced during infection, the bacteria need to balance this energy-consuming task with other physiological processes. However, it has remained poorly understood how toxins can impact gene expression to trigger such adaptations. We found that specific members of a toxin family in the major human pathogen Staphylococcus aureus have evolved for gene regulatory purposes. These specific toxins interact with a DNA-binding regulator protein to enable production of the toxin export machinery and ascertain that the machinery is not expressed when toxins are not made and it is not needed. Our study gives mechanistic insight into how toxins may directly adjust bacterial physiology to times of toxin production during infection.
authors: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Hwang-Soo
authors: HS
authors: Joo
authors: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Som S
authors: SS
authors: Chatterjee
authors: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Amer E
authors: AE
authors: Villaruz
authors: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Seth W
authors: SW
authors: Dickey
authors: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Vee Y
authors: VY
authors: Tan
authors: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Yan
authors: Y
authors: Chen
authors: Genomics Unit, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
authors: Daniel E
authors: DE
authors: Sturdevant
authors: Genomics Unit, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
authors: Stacy M
authors: SM
authors: Ricklefs
authors: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA motto@niaid.nih.gov.
authors: Michael
authors: M
authors: Otto
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D025941:Protein Interaction Mapping; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D012097:Repressor Proteins; C025971:staphylococcal delta toxin