Owusu-Anim Daniel, Kwon Dong H
Department of Biology, Long Island University, New York, USA.
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.
Adv Microbiol. 2012 Mar 1;2(1). doi: 10.4236/aim.2012.21005.
Polymyxins are often considered as a last resort to treat multidrug resistant but polymyxin resistance has been increasingly reported worldwide in clinical isolates. Polymyxin resistance in is known to be associated with alterations in either PhoQ or PmrB. In this study, mutant strains of 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 is caused by alterations of both PhoQ and PmrB.
多粘菌素通常被视为治疗多重耐药菌的最后手段,但全球临床分离株中多粘菌素耐药性的报道日益增多。已知大肠杆菌中的多粘菌素耐药性与PhoQ或PmrB的改变有关。在本研究中,构建了携带氨基酸替代、PhoQ和PmrB单失活和/或双失活的大肠杆菌突变株,以进一步了解PhoQ和PmrB在多粘菌素敏感性中的作用。PhoQ的失活和/或氨基酸替代均可导致多粘菌素B耐药,但只有PmrB的氨基酸替代会导致耐药。PhoQ和PmrB的改变导致的多粘菌素B耐药水平高于单独改变PhoQ或PmrB。时间杀菌试验证实了这些结果,表明大肠杆菌中的高水平多粘菌素耐药是由PhoQ和PmrB的改变引起的。