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.