biostudies-literatureUnknown60(6)Cheng YHNational Taiwan University HospitalMinistry of Science and Technology, TaiwanNational Taiwan University Hospital-Taipei Veterans General Hospital Joint Research ProgramNational Taiwan UniversityLiver Disease Prevention and Treatment Research Foundation in TaiwanColistin is a last-resort antibiotic for treatment of carbapenem-resistant Klebsiella pneumoniae A recent study indicated that missense mutations in the CrrB protein contribute to colistin resistance. In our previous study, mechanisms of colistin resistance were defined in 17 of 26 colistin-resistant K. pneumoniae clinical isolates. Of the remaining nine strains, eight were highly resistant to colistin. In the present study, crrAB sequences were determined for these eight strains. Six separate amino acid substitutions in CrrB (Q10L, Y31H, W140R, N141I, P151S, and S195N) were detected. Site-directed mutagenesis was used to generate crrB loci harboring individual missense mutations; introduction of the mutated genes into a susceptible strain, A4528, resulted in 64- to 1,024-fold increases inAntimicrobial agents and chemotherapy3709-16https://www.ebi.ac.uk/biostudies/studies/S-EPMC4879426biostudies-literatureAmino Acid Substitutions of CrrB Responsible for Resistance to Colistin through CrrC in Klebsiella pneumoniae.PMC4879426Lin YTWang JTCheng YHLin TLfalseAmino Acid Substitutions of CrrB Responsible for Resistance to Colistin through CrrC in Klebsiella pneumoniae.Colistin is a last-resort antibiotic for treatment of carbapenem-resistant Klebsiella pneumoniae A recent study indicated that missense mutations in the CrrB protein contribute to colistin resistance. In our previous study, mechanisms of colistin resistance were defined in 17 of 26 colistin-resistant K. pneumoniae clinical isolates. Of the remaining nine strains, eight were highly resistant to colistin. In the present study, crrAB sequences were determined for these eight strains. Six separate amino acid substitutions in CrrB (Q10L, Y31H, W140R, N141I, P151S, and S195N) were detected. Site-directed mutagenesis was used to generate crrB loci harboring individual missense mutations; introduction of the mutated genes into a susceptible strain, A4528, resulted in 64- to 1,024-fold increases in2016-01-01T00:00:00Z2016 Jun2026-05-30T10:40:43.525Z2025-04-05T12:22:59.171ZS-EPMC48794262706731610.1128/AAC.00009-1610.1128/aac.00009-16