Open AccessA single amino acid substitution in PmrB is associated with polymyxin B resistance in clinical isolate of Pseudomonas aeruginosa
Author(s) -
Abraham Neethu,
Kwon Dong H.
Publication year - 2009
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.2009.01720.x
Subject(s) - pseudomonas aeruginosa , polymyxin , microbiology and biotechnology , amino acid substitution , polymyxin b , pseudomonadaceae , bacteria , pseudomonadales , biology , chemistry , antibiotics , genetics , mutation , gene
Pseudomonasaeruginosa 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 molecular details of polymyxin resistance we characterized polymyxin B‐resistant clinical isolate of P. aeruginosa . The clinical isolate grew with 4 μg mL −1 of polymyxin B while a reference P. aeruginosa PAO1 grew with 0.25 μg mL −1 . Polymyxin B susceptibility was restored (minimal inhibitory concentration from 8 to 0.5 μg mL −1 ) 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 isolates of P. aeruginosa .