ATR in EHEC 0157:H7 and the cross-protection effects thus induced lead to the uncertainty of food safety. This study aimed to identify factors that are associated with the ATR in EHEC 0157:H7 under stomach acidity using RNA-seq. In total, 223 DEGs in E. coil 0157:H7 and 110 DEG5 in E. coli after acid treatment were identified, including 118 upregulated and 105 downregulated in EHEC 0157:H7, and 89 upregulated and 21 downregulated in E. coil ATCC 25922. According to our results, when facing the ATR environment, protein Asr regulated the whole add resistance process. In E. coli ATCC 25922, cadA and cadB mediate the lysine decarboxylation consumed the extra protons inside and keep the neutral pH value in cytoplasm to protect the E. coli from death. In contrast, oxidation-reduction mediated by ahpC, which was activated by the depression of oxyR, and hydrogenation mediated by mhpA consumed the protons inside keeping the neutral pH value to protect the EHEC 0157:H7 from harm induced by a low pH environment. In addition, EHEC 0157:H7 expressed more anti-oxidation enzymes to repair damage caused by acid stress, which enhanced its resistance to acid compared to E. coli ATCC 25922. (c) 2017 Elsevier Ltd. All rights reserved.