Moritz Elizabeth M, Hergenrother Paul J
Department of Microbiology, Roger Adams Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):311-6. doi: 10.1073/pnas.0601168104. Epub 2006 Dec 26.
Vancomycin-resistant enterococci (VRE) are common hospital pathogens that are resistant to most major classes of antibiotics. The incidence of VRE is increasing rapidly, to the point where over one-quarter of enterococcal infections in intensive care units are now resistant to vancomycin. The exact mechanism by which VRE maintains its plasmid-encoded resistance genes is ill-defined, and novel targets for the treatment of VRE are lacking. In an effort to identify novel protein targets for the treatment of VRE infections, we probed the plasmids obtained from 75 VRE isolates for the presence of toxin-antitoxin (TA) gene systems. Remarkably, genes for one particular TA pair, the mazEF system (originally identified on the Escherichia coli chromosome), were present on plasmids from 75/75 (100%) of the isolates. Furthermore, mazEF was on the same plasmid as vanA in the vast majority of cases (>90%). Plasmid stability tests and RT-PCR raise the possibility that this plasmid-encoded mazEF is indeed functional in enterococci. Given this ubiquity of mazEF in VRE and the deleterious activity of the MazF toxin, disruption of mazEF with pharmacological agents is an attractive strategy for tailored antimicrobial therapy.
耐万古霉素肠球菌（VRE）是常见的医院病原体，对大多数主要类别的抗生素具有抗性。VRE的发病率正在迅速上升，以至于重症监护病房中超过四分之一的肠球菌感染现在对万古霉素具有抗性。VRE维持其质粒编码抗性基因的确切机制尚不清楚，并且缺乏治疗VRE的新靶点。为了确定治疗VRE感染的新蛋白质靶点，我们检测了从75株VRE分离株获得的质粒中是否存在毒素-抗毒素（TA）基因系统。值得注意的是，一种特定TA对的基因，即mazEF系统（最初在大肠杆菌染色体上鉴定），存在于75/75（100%）分离株的质粒上。此外，在绝大多数情况下（>90%），mazEF与vanA位于同一质粒上。质粒稳定性测试和逆转录-聚合酶链反应（RT-PCR）增加了这种质粒编码的mazEF在肠球菌中确实具有功能的可能性。鉴于mazEF在VRE中如此普遍存在以及MazF毒素的有害活性，用药物破坏mazEF是一种有吸引力的定制抗菌治疗策略。
