## 5 Short-Chain Organic Acid Stress  
_E. coli_ and _L. monocytogenes_ are both food-borne pathogens, and their abilities to survive and thrive under organic acid stress are critical for the successful transmission from food to human beings. Food-grade organic acids are often used as food preservatives and organic acids are also fermentation products that can be naturally present in raw food or formed during fermentation processes. Moreover, upon ingestion of contaminated food products, the highly acidic stomach environment (pH 1-3) represents a great challenge to the survival of these bacteria. This is followed by a passage through mildly acidic to neutral environment in the intestine, where organic acids (e.g., bile acid) are abundant [138]. Weak organic acids are found to be more potent against bacteria especially under mildly acidic conditions when the acid groups are more likely to be protonated [139]. Depending on the type of acid, the modes of action can differ considerably; however, the common mechanism involves alteration of the pH\({}_{i}\) and the accumulation of the weak acid anions in the cytoplasm. At low pH, the undissociated (protonated and uncharged) form of a weak acid diffuses through the cell membrane and dissociates intracellularly, acidifying the intracellular pH [143; 144; 140; 141; 142; 143]. Meanwhile, dissociated acid anions accumulate within the cell and can cause turgor stress due to an increase in osmotic pressure [144]. Depending on the anion, accumulated acid might interrupt cellular processes [144; 145], uncouple the proton motive force [146; 147], decrease cell motility [148], and potentially disrupt the function of the membrane [149; 150; 151]. Both pathogenic (e.g., strain O157:H7) and non-pathogenic (e.g., strain K-12) _E. coli_ upregulate genes involved in oxidative stress, cell envelope, cold shock stress, and iron and manganese uptake as a common response to HCl, acetate acid, and lactic acid stress [152]. Interestingly, strain-specific acid stress response genes mostly fall in the same functional categories as the universal acid response, indicating that different _E. coli_ strains have evolved different genetic strategies to cope with the same stress [152]. In _L. monocytogenes_, a more significant overlap in gene regulation was observed when bacteria were exposed to these three acids, including upregulation of the GAD system, membrane modification, DNA damage repair, proteases and chaperonins, histidine synthesis, potassium uptake, and general stress proteins [153]. Both species upregulate cell envelope stress, oxidative stress, and DNA damage related genes, pinpointing the conserved nature of the acid stress response mechanisms among remotely related species. In both _E. coli_ and _L. monocytogenes_, lactic acid is a product of fermentative metabolism and it specifically induces the expression of a large set of genes, which overlaps significantly with the transcriptomic response to HCl [152; 153; 154; 155], suggesting that similar stress response mechanisms are activated by these two acids. In _L. monocytogenes_, lactic acid uniquely induced differential expression of most genes among five tested weak acids (acetic acid, benzoic acid, citric acid, sorbic acid, and lactic acid) ([PERSON] and [PERSON], unpublished data), and these findings are also supported by the observations from [PERSON] et al. [153]. In a recent transcriptomic study on _L. monocytogenes_, lactic acid exposure resulted in major change in gene expression (\(\sim\)2/3 of genome differentially expressed) [109]. Two lineage II strains (ST8 and ST121) shared most of the differentially regulated genes, which is probably not surprising due to the highly stable core genome of this species. In contrast, acetate acid exposure results in differential regulation of a much smaller set of genes in both species compared to the expression profile observed upon exposure to other organic acids [152; 153]. In _E.