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In the aquaculture industry, feed acidifiers have been used to increase the growth of aquatic animals. However, there is limited study on the effects of acidic condition on the virulence and survival of pathogens in aquaculture. In this study, we investigated the survival ability of <jats:italic>Vibrio<\/jats:italic> <jats:italic>parahaemolyticus<\/jats:italic> at lethal acidic pH (4.0) after adapted the bacteria to sub\u2010lethal acidic pH (5.5) for 1\u00a0hr. Our results indicated that the adapted strain increased the survival ability at lethal acidic pH invoked by an inorganic (HCl) or organic (citric) acid. RNA\u2010sequencing (RNA\u2010seq) results revealed that 321 genes were differentially expressed at the sub\u2010lethal acidic pH including <jats:italic>cadC<\/jats:italic>, <jats:italic>cadBA<\/jats:italic> and <jats:italic>groES<\/jats:italic>\/g<jats:italic>roEL<\/jats:italic> relating to acid tolerance response (ATR), as well as genes relating to outer membrane, heat\u2010shock proteins, phosphotransferase system and flagella system. Quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) confirmed that <jats:italic>cadC<\/jats:italic> and <jats:italic>cadBA<\/jats:italic> were upregulated under sub\u2010lethal acidic conditions. The CadC protein could directly regulate the expression of <jats:italic>cadBA<\/jats:italic> to modulate the ATR in <jats:italic>V<\/jats:italic>.\u00a0<jats:italic>parahaemolyticus<\/jats:italic>. RNA\u2010seq data also indicated that 113 genes in the CadC\u2010dependent way and 208 genes in the CadC\u2010independent way were differentially expressed, which were related to the regulation of ATR. Finally, the motility and cytotoxicity of the sub\u2010lethal acidic adapted wild type (WT) were significantly increased compared with the unadapted strain. Our results demonstrated that the dietary acidifiers may increase the virulence and survival of <jats:italic>V<\/jats:italic>.\u00a0<jats:italic>parahaemolyticus<\/jats:italic> in aquaculture.<\/jats:p>","DOI":"10.1111\/jfd.13376","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T21:15:29Z","timestamp":1617916529000},"page":"1155-1168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>Vibrio parahaemolyticus<\/i> CadC regulates acid tolerance response to enhance bacterial motility and cytotoxicity"],"prefix":"10.1111","volume":"44","author":[{"given":"Dan","family":"Gu","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Zoonosis\/Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou University Jiangsu China"},{"name":"Key Laboratory of Prevention and Control of Biological Hazard Factors 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