title: The medium-/long-chain fatty acyl-CoA dehydrogenase (fadF) gene of Salmonella typhimurium is a phase 1 starvation-stress response (SSR) locus.
abstract: Salmonella enterica serovar Typhimurium (S. typhimurium) is an enteric pathogen that causes significant morbidity in humans and other mammals. During their life cycle, salmonellae must survive frequent exposures to a variety of environmental stresses, e.g. carbon-source (C) starvation. The starvation-stress response (SSR) of S. typhimurium encompasses the genetic and physiological realignments that occur when an essential nutrient becomes limiting for bacterial growth. The function of the SSR is to produce a cell capable of surviving long-term starvation. This paper reports that three C-starvation-inducible lac fusions from an S. typhimurium C-starvation-inducible lac fusion library are all within a gene identified as fadF, which encodes an acyl-CoA dehydrogenase (ACDH) specific for medium-/long-chain fatty acids. This identification is supported by several findings: (a) significant homology at the amino acid sequence level with the ACDH enzymes from other bacteria and eukaryotes, (b) undetectable beta-oxidation levels in fadF insertion mutants, (c) inability of fad insertion mutants to grow on oleate or decanoate as a sole C-source, and (d) inducibility of fadF::lac fusions by the long-chain fatty acid oleate. In addition, the results indicate that the C-starvation-induction of fadF is under negative control by the FadR global regulator and positive control by the cAMP:cAMP receptor protein complex and ppGpp. It is also shown that the fadF locus is important for C-starvation-survival in S. typhimurium. Furthermore, the results demonstrate that fadF is induced within cultured Madin-Darby canine kidney (MDCK) epithelial cells, suggesting that signals for its induction (C-starvation and/or long-chain fatty acids) may be present in the intracellular environment encountered by S. typhimurium. However, fadF insertion mutations did not have an overt effect on mouse virulence.
authors: Department of Biomedical Sciences, University of South Alabama, Mobile, AL 36688, USA.
authors: Michael P
authors: MP
authors: Spector
authors: Department of Biochemistry and Molecular Biology, The Albany Medical College, Albany, NY 12208, USA.
authors: Concetta C
authors: CC
authors: DiRusso
authors: Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AY, UK.
authors: Mark J
authors: MJ
authors: Pallen
authors: Biotechnology Laboratory and Departments of Biochemistry and Microbiology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
authors: Francisco Garcia
authors: FG
authors: Del Portillo
authors: Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AY, UK.
authors: Gordon
authors: G
authors: Dougan
authors: Biotechnology Laboratory and Departments of Biochemistry and Microbiology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
authors: B Brett
authors: BB
authors: Finlay
mesh_terms: D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D002352:Carrier Proteins; D002460:Cell Line; D002874:Chromosome Mapping; D002373:Cyclic AMP Receptor Protein / Q000235:genetics / Q000502:physiology; D004285:Dogs; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006159:Guanosine Tetraphosphate / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000382:microbiology; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D012808:Sigma Factor / Q000235:genetics / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; C057119:FadR protein, Bacteria; D005227:Fatty Acids; D012097:Repressor Proteins; D012808:Sigma Factor; D006159:Guanosine Tetraphosphate; D002244:Carbon; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain