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

Salmonella enterica serovar Typhimurium (S. typhimurium) is an enteric path ogen 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 starvatio n-stress response (SSR) of S, typhimurium encompasses the genetic and physi ological realignments that occur when an essential nutrient becomes limitin g for bacterial growth. The function of the SSR is to produce a cell capabl e of surviving long-term starvation. This paper reports that three C-starva tion-inducible lac fusions from an S, typhimurium C-starvation-inducible la c 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 homo logy at the amino acid sequence level with the ACDH enzymes from other bact eria and eukaryotes, (b) undetectable beta-oxidation levels in fadF inserti on mutants, (c) inability of fad insertion mutants to grow on oleate or C-s tarvation-induction of fadF is under negative control by the FadR global re gulator 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-s urvival in 5, typhimurium. Furthermore, the results demonstrate that fadF i s 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 b y 5. typhimurium. However, fadF insertion mutations did not have an overt e ffect on mouse virulence.