Cooperative Interaction between Acid and Copper Resistance in Escherichia coli

The persistence of pathogenic under acidic conditions poses a serious risk to food safety, especially in acidic foods such as kimchi. To identify the bacterial factors required for acid resistance, transcriptomic analysis was conducted on an acid-resistant enterotoxigenic strain and the genes with significant changes in their expression under acidic pH were selected as putative resistance factors against acid stress. These genes included those associated with a glutamatedependent acid resistance (GDAR) system and copper resistance. strains lacking GadA, GadB, or YbaST, the components of the GDAR system, exhibited significantly attenuated growth and survival under acidic stress conditions. Accordantly, the inhibition of the GDAR system by 3-mercaptopropionic acid and aminooxyacetic acid abolished bacterial adaptation and survival under acidic conditions, indicating the indispensable role of a GDAR system in acid resistance. Intriguingly, the lack of encoding a transcriptional regulator for copper resistance genes markedly impaired bacterial resistance to acid stress as well as copper. Conversely, the absence of YbaST severely compromised bacterial resistance against copper, suggesting an interplay between acid and copper resistance. These results suggest that a GDAR system can be a promising target for developing control measures to prevent resistance to acid and copper treatments.