title: Differential Role of Two-Component Regulatory Systems (phoPQandpmrAB) in Polymyxin B Susceptibility ofPseudomonas aeruginosa.
abstract: Polymyxins are often considered as a last resort to treat multidrug resistantP. aeruginosabut polymyxin resistance has been increasingly reported worldwide in clinical isolates. Polymyxin resistance inP. aeruginosais known to be associated with alterations in either PhoQ or PmrB. In this study, mutant strains ofP. aeruginosacarrying amino acid substitution, a single and/or dual inactivation of PhoQ and PmrB were constructed to further understand the roles of PhoQ and PmrB in polymyxin susceptibility. Polymyxin B resistance was caused by both inactivation and/or amino acid substitutions in PhoQ but by only amino acid substitutions of PmrB. Alterations of both PhoQ and PmrB resulted in higher levels of polymyxin B resistance than alteration of either PhoQ or PmrB alone. These results were confirmed by time-killing assays suggesting that high-level polymyxin resistance inP. aeruginosais caused by alterations of both PhoQ and PmrB.
authors.affiliation: Department of Biology, Long Island University, New York, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Owusu-Anim
authors.affiliation: Department of Biology, Long Island University, New York, USA ; Department of Medicine of Michael E DeBakey VA Medical Center, Baylor College of Medicine, Houston, USA.
authors.forename: Dong H
authors.initials: DH
authors.lastname: Kwon
keywords: Polymyxin B Resistance; Pseudomonas aeruginosa; phoPQ; pmrAB