The chaperone DnaK promotes the emergence and accumulation of antibiotic-resistant clones through its ATPase activity in Riemerella anatipestifer.

The rapid emergence of antibiotic-resistant bacteria has become a global concern. In particular, the overuse of antibiotics in the breeding industry has accelerated the emergence of antibiotic-resistant bacteria, but the mechanisms driving this phenomenon are not fully understood. Here, using the multidrug-resistant bacterium R. anatipestifer as a proof of concept, we show that the chaperone DnaK promoted the emergence and accumulation of antibiotic-resistant clones. Compared to the ∆dnaK, the wild type produced more resistant clones under antibiotic stress and accelerated the accumulation of resistance mutations under the second antibiotic stress. Importantly, it was indicated that the broad DnaK molecular chaperone inhibitor, telaprevir (TP), effectively decreases the frequency of antibiotics resistant (FOR) in R. anatipestifer through inhibiting the ATPase activation of the DnaK molecular chaperone. Taken together, this study suggested that the chaperone DnaK can be used as a target for drug design to control the emergence and accumulation of antibiotic-resistant clones in R. anatipestifer and reduce the risk of antibiotic resistance in clinical treatment.