The medium-/long-chain fatty acyl-CoA dehydrogenase (fadF) gene of Salmonella typhimurium is a phase 1 starvation-stress response (SSR) locus

Microbiology (Reading). 1999 Jan:145 ( Pt 1):15-31. doi: 10.1099/13500872-145-1-15.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyl-CoA Dehydrogenase
  • Acyl-CoA Dehydrogenase, Long-Chain / chemistry
  • Acyl-CoA Dehydrogenase, Long-Chain / genetics*
  • Acyl-CoA Dehydrogenase, Long-Chain / metabolism
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Carbon / metabolism
  • Carrier Proteins
  • Cell Line
  • Chromosome Mapping
  • Cyclic AMP Receptor Protein / genetics
  • Cyclic AMP Receptor Protein / physiology
  • Dogs
  • Fatty Acids / metabolism
  • Female
  • Guanosine Tetraphosphate / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Salmonella Infections, Animal / microbiology
  • Salmonella typhimurium / enzymology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / pathogenicity
  • Salmonella typhimurium / physiology*
  • Sequence Homology, Amino Acid
  • Sigma Factor / genetics
  • Sigma Factor / physiology

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Cyclic AMP Receptor Protein
  • FadR protein, Bacteria
  • Fatty Acids
  • Repressor Proteins
  • Sigma Factor
  • Guanosine Tetraphosphate
  • Carbon
  • Acyl-CoA Dehydrogenase
  • Acyl-CoA Dehydrogenase, Long-Chain