AcrAB Efflux Pump Plays a Crucial Role in Bile Salts Resistance and Pathogenesis of Klebsiella pneumoniae

Bile salts possess innate antibacterial properties and can cause significant damage to bacteria. To survive in the mammalian gut, <i>Klebsiella pneumoniae</i> has developed mechanisms to tolerate bile salts; however, the specific mechanisms remain unclear. Transposon library screening revealed that the efflux pump AcrAB is involved in bile salt resistance. <i>acrA</i> and <i>acrB</i> mutants exhibited high sensitivity not only to bile salts but also to SDS and various antibiotics, with a switch-loop, comprising residues G615, F616, A617, and G618, proving to be crucial in this process. A colonization defect of <i>acrA</i> and <i>acrB</i> mutants was demonstrated to be located in the mouse small intestine, where the bile salt concentration is higher compared to the large intestine. Additionally, both <i>acrA</i> and <i>acrB</i> mutants displayed reduced virulence in the <i>Galleria mellonella</i> model. In conclusion, our results suggest that the Resistance-Nodulation-Cell Division efflux pump serves as a critical determinant in the pathogenesis of <i>K. pneumoniae</i> through various aspects.