H-NS controls the susceptibility ofto aminoglycosides by interfering its uptake and efflux.

Abstract

H-NS is a histone-like nucleoid-structuring protein that regulates gene expressions, particularly acquired foreign genes, however, little is known about whether H-NS can modulate bacterial susceptibility by regulating its intrinsic genes. The-deleted mutant EΔ, the-complemented strain EΔ/pand the-overexpressed strain E/pwere derivatives ofATCC 25922, the susceptibility of which were assessed by the broth microdilution method and time-kill curves assays. We found that the MICs for strain EΔagainst gentamicin and amikacin were significantly decreased by 8-16 folds in contrast toATCC 25922. Further studies displayed that the absence ofcaused damage to the bacterial outer membrane and increased the expression levels of porin-related genes, such as, and, thus obviously enhancing aminoglycosides uptake of strain EΔ. Meanwhile,deletion also led to remarkable inhibition of the efflux pumps activity and decreased expressions of efflux-related genes, and, which reduced the efflux of aminoglycosides. In addition, the activation of glycolysis and electron transport chain, as well as the reduction of Δψ dissipation, could lead to a remarkable increase in proton motive force (PMF), thus further inducing more aminoglycosides uptake by strain EΔ. Our findings reveal that H-NS regulates the resistance ofto aminoglycosides by influencing its uptake and efflux, which will enrich our understanding of the mechanism by which H-NS modulates bacterial resistance.