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

Autor: Dong H. Kwon, Neethu Abraham
Rok vydání: 2009
Předmět:
Zdroj: FEMS Microbiology Letters. 298:249-254
ISSN: 1574-6968
0378-1097
DOI: 10.1111/j.1574-6968.2009.01720.x
Popis: 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 molecular details of polymyxin resistance we characterized polymyxin B-resistant clinical isolate of P. aeruginosa. The clinical isolate grew with 4 microg mL(-1) of polymyxin B while a reference P. aeruginosa PAO1 grew with 0.25 microg mL(-1). Polymyxin B susceptibility was restored (minimal inhibitory concentration from 8 to 0.5 microg 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.
Databáze: OpenAIRE