Cross-resistance between tigecycline and cephalosporins regulated by expression of ompK35 and ompK36 in Klebsiella pneumoniae

We investigated the relationship of antibiotic susceptibility changes by subsequent exposure of tigecycline and cephalosporins. In addition to colistin, meropenem, ciprofloxacin, and ampicillin, minimum inhibitory concentrations (MICs) of cephalosporins such as ceftazidime and cefotaxime increased with acquisition of tigecycline resistance. When the K. pneumoniae strains were exposed to cephalosporins, their tigecycline MICs also increased with the acquisition of cephalosporin resistances. The cephalosporin-resistant mutants as well as tigecycline-resistant mutants showed decreased expression of ompK35 and ompK36, despite no genetic alternations. The antibiotic-resistant mutants that have restored the expression level of the genes by cloning of ompK35 or ompK36 recovered their antibiotic susceptibilities, although there were some deviations for each antibiotic. Our findings suggest that the cross-resistance between tigecycline and cephalosporins may be regulated by expression of porin genes. It makes more careful consideration to selecting antibiotics to treat bacterial infections.