## 5 Short-Chain Organic Acid Stress
coli_, acetate specifically induces genes involved in metabolism [156; 157], and multidrug and aromatic carboxylic acid efflux [152]. It is however surprising that genes in the acid fitness island (AFI), which includes _slp_, _hdeB_, _hdeA_, _gadE_, _mdtE_, and _gadA_, were down regulated in _E. coli_ K-12 when exposed to acetic acid [152]. Acetate accumulation has been investigated in _E. coli_ and concentrationscan get as high as 230 mM inside the cell when the extracellular concentration is only 8 mM. This turgor stress is thought to be partially relieved by reducing intracellular glutamate concentration [144]. Further investigations showed that the inhibitory effect of acetic acid on _E. coli_ in chemically defined media is largely attributed to interruption of methionine biosynthesis and concomitant accumulation of the toxic metabolite homocysteine [145], which is itself inhibitory because it perturbs branched chain amino acid biosynthesis [158]. Recently, the transhydrogenase UdhA was identified as an important source of NADH for the growth of _E. coli_ on acetate and plays a positive role in the regulation of expression of the GAD system [159]. In _L. monocytogenes_, two studies have revealed significant strain to strain variation in the transcriptomic response to acetate [40; 41]. Nevertheless, upregulation of branch-chain fatty acid synthesis related genes appears as one common response to acetate stress in this species [40]. Benzoic acid is a partial uncoupler that disrupts the proton motive force in _E. coli_[160]. Exposure to benzoic acid in _E. coli_ induces the AFI genes and the GadE regulon. Interestingly, evolution in the presence of growth permissive concentration of benzoic acid selected for strains that lost GAD activity [160; 161]. This phenomenon is thought to be explained by the fitness cost of activating protective mechanisms that fail to provide benefit. Indeed, the GAD system was found to provide protection against lethal acetate acid stress in _E. coli_[152] and does not contribute significantly to the growth of _L. monocytogenes_ in the presence of acetate, benzoate, and sorbate [162]. In the latter species, benzoic acid specifically induces genes involved in carbohydrate metabolism, transport/binding proteins, lipoproteins, and multidrug efflux pump MdrL ([PERSON] and [PERSON], unpublished data). Another important group of organic acids that are present in the human GI tract are bile acids. _E. coli_ can reduce the toxicity of bile acids by means of a 7\(\alpha\) -hydroxysteroid dehydrogenase [163; 164] and their active efflux via the AcrAB and EmrAB multidrug efflux systems [165]. _L. monocytogenes_ encodes a bile salt hydrolase which is absent in the non-pathogenic species _L. innocua_[166]. Similar to _E. coli_, multidrug efflux systems were also found to be involved in bile acids stress response in _L. monocytogenes_[167; 168]. An increased sensitivity to bile acids was observed in _L. monocytogenes_ at acidic pH [169] but bacteria displayed an enhanced resistance to bile acids when bacteria were pre-adapted to several stresses [170]. Numerous mechanisms of bile acids stress response in _L. monocytogenes_ were reviewed by [PERSON] et al. [171]. Interestingly, genes related to osmotic stress are found differentially regulated under organic acid stress in both species. In _E. coli_, genes involved in proline accumulation and osmotically inducible genes are upregulated in O157:H7 [152; 156]. In _L. monocytogenes_, _sigL_ and genes involved in carnitine/betaine and potassium uptake are upregulated [153]. SigL and the carnitine transporter are indeed confirmed to play a role in organic acid stress response [172]. In addition, multiple osmolyte transporter (-like) systems have been demonstrated to contribute to bile acids tolerance [173; 174].