title: Identification of a two-component fatty acid kinase responsible for host fatty acid incorporation by Staphylococcus aureus.
abstract: Extracellular fatty acid incorporation into the phospholipids of Staphylococcus aureus occurs via fatty acid phosphorylation. We show that fatty acid kinase (Fak) is composed of two dissociable protein subunits encoded by separate genes. FakA provides the ATP binding domain and interacts with two distinct FakB proteins to produce acyl-phosphate. The FakBs are fatty acid binding proteins that exchange bound fatty acid/acyl-phosphate with fatty acid/acyl-phosphate presented in detergent micelles or liposomes. The ΔfakA and ΔfakB1 ΔfakB2 strains were unable to incorporate extracellular fatty acids into phospholipid. FakB1 selectively bound saturated fatty acids whereas FakB2 preferred unsaturated fatty acids. Affymetrix array showed a global perturbation in the expression of virulence genes in the ΔfakA strain. The severe deficiency in α-hemolysin protein secretion in ΔfakA and ΔfakB1 ΔfakB2 mutants coupled with quantitative mRNA measurements showed that fatty acid kinase activity was required to support virulence factor transcription. These data reveal the function of two conserved gene families, their essential role in the incorporation of host fatty acids by Gram-positive pathogens, and connects fatty acid kinase to the regulation of virulence factor transcription in S. aureus.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105; and.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Parsons
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105; and.
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Broussard
authors.affiliation: Department of Pathology and Microbiology, Center for Staphylococcal Research, University of Nebraska Medical Center, Omaha, NE 68198.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Bose
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105; and.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Rosch
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105; and.
authors.forename: Pamela
authors.initials: P
authors.lastname: Jackson
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105; and.
authors.forename: Chitra
authors.initials: C
authors.lastname: Subramanian
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105; and charles.rock@stjude.org.
authors.forename: Charles O
authors.initials: CO
authors.lastname: Rock
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000378:metabolism; D017851:Phosphotransferases (Carboxyl Group Acceptor) / Q000737:chemistry / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000472:pathogenicity; D013379:Substrate Specificity; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D005227:Fatty Acids; D010743:Phospholipids; D037521:Virulence Factors; D017851:Phosphotransferases (Carboxyl Group Acceptor)