Differential Role of Two-Component Regulatory Systems (phoPQ and pmrAB) in Polymyxin B Susceptibility of Pseudomonas aeruginosa.
Differential Role of Two-Component Regulatory Systems (phoPQ and pmrAB) in Polymyxin B Susceptibility of Pseudomonas aeruginosa.
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DOI：
10.4236/aim.2012.21005
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发表时间：
2012-03-01
期刊：
影响因子：
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通讯作者：
Kwon, Dong H
中科院分区：
文献类型：
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作者：
Owusu-Anim, Daniel;Kwon, Dong H
多粘菌素通常被认为是治疗多药耐药铜绿假单胞菌的最后手段，但多粘菌素耐药性已在全球范围内越来越多地报告临床分离株。已知铜绿假单胞菌中的多粘菌素抗性与PhoQ或PmrB的改变相关。本研究构建了PhoQ和PmrB氨基酸置换、单失活和/或双失活的铜绿假单胞菌突变株，以进一步了解PhoQ和PmrB在多粘菌素敏感性中的作用。多粘菌素B抗性由PhoQ中的失活和/或氨基酸取代引起，但仅由Pmr B的氨基酸取代引起。PhoQ和Pmr B两者的改变导致比单独的PhoQ或Pmr B的改变更高水平的多粘菌素B抗性。这些结果通过时间杀灭试验证实，表明铜绿假单胞菌中高水平的多粘菌素耐药性是由PhoQ和PmrB的改变引起的。
Polymyxins are often considered as a last resort to treat multidrug resistant P. aeruginosa but polymyxin resistance has been increasingly reported worldwide in clinical isolates. Polymyxin resistance in P. aeruginosa is known to be associated with alterations in either PhoQ or PmrB. In this study, mutant strains of P. aeruginosa carrying 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 in P. aeruginosa is caused by alterations of both PhoQ and PmrB.