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Vet. Sci."],"abstract":"<jats:p>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 <jats:italic>hns<\/jats:italic>-deleted mutant E\u0394<jats:italic>hns<\/jats:italic>, the <jats:italic>hns<\/jats:italic>-complemented strain E\u0394<jats:italic>hns<\/jats:italic>\/p<jats:italic>hns<\/jats:italic> and the <jats:italic>hns<\/jats:italic>-overexpressed strain E\/p<jats:italic>hns<\/jats:italic> were derivatives of <jats:italic>Escherichia coli<\/jats:italic> ATCC 25922, the susceptibility of which were assessed by the broth microdilution method and time-kill curves assays. We found that the MICs for strain E\u0394<jats:italic>hns<\/jats:italic> against gentamicin and amikacin were significantly decreased by 8\u201316 folds in contrast to <jats:italic>E. coli<\/jats:italic> ATCC 25922. Further studies displayed that the absence of <jats:italic>hns<\/jats:italic> caused damage to the bacterial outer membrane and increased the expression levels of porin-related genes, such as <jats:italic>ompC, ompF, ompG<\/jats:italic>, and <jats:italic>ompN<\/jats:italic>, thus obviously enhancing aminoglycosides uptake of strain E\u0394<jats:italic>hns<\/jats:italic>. Meanwhile, <jats:italic>hns<\/jats:italic> deletion also led to remarkable inhibition of the efflux pumps activity and decreased expressions of efflux-related genes <jats:italic>clbM, acrA, acrB, acrD<\/jats:italic>, and <jats:italic>emrE<\/jats:italic>, which reduced the efflux of aminoglycosides. In addition, the activation of glycolysis and electron transport chain, as well as the reduction of \u0394\u03c8 dissipation, could lead to a remarkable increase in proton motive force (PMF), thus further inducing more aminoglycosides uptake by strain E\u0394<jats:italic>hns<\/jats:italic>. Our findings reveal that H-NS regulates the resistance of <jats:italic>E. coli<\/jats:italic> to aminoglycosides by influencing its uptake and efflux, which will enrich our understanding of the mechanism by which H-NS modulates bacterial resistance.<\/jats:p>","DOI":"10.3389\/fvets.2025.1534498","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T15:10:41Z","timestamp":1738854641000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["H-NS controls the susceptibility of Escherichia coli to aminoglycosides by interfering its uptake and 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