A single amino acid substitution in PmrB is associated with polymyxin B resistance in clinical isolate of Pseudomonas aeruginosa.

摘要

Pseudomonas aeruginosa is a major causative agent of hospital-acquired infections and infections in cystic fibrosis patients. Treatment of P. aeruginosa is complicated by the presence of intrinsic and acquired multidrug resistant isolates. Polymyxin B has often been used as the last option to treat the multidrug resistant isolates. However, polymyxin B resistant clinical isolates have been increasingly reported worldwide. To understand the molecular details of polymyxin resistance I characterized polymyxin B resistant clinical isolate of P. aeruginosa. The clinical isolate grew with 4 mug/mL of polymyxin B while a reference P. aeruginosa PAO1 grew with 0.25 mug/mL. Polymyxin B susceptibility was restored (MIC from 8 to 0.5 mug/mL) by an intact clone of pmrAB but not by an intact clone of phoPQ, or the cloning vector. DNA sequence analysis of pmrB from the resistant isolate revealed a single nucleotide substitution (T to C) substituted methionine to threonine at position 292 of PmrB. Involvement of this amino acid substitution in polymyxin B resistance was confirmed by complementation of a pmrAB null-mutant strain with the pmrAB containing the amino acid substitution. These results suggest that amino acid substitution in PmrB is one mechanism of polymyxin B resistance in clinical isolate of P. aeruginosa.