Weber Brent S, Ly Pek Man, Irwin Joshua N, Pukatzki Stefan, Feldman Mario F
Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada T6G 2G2; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110;
Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada T6G 2G2;
Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):9442-7. doi: 10.1073/pnas.1502966112. Epub 2015 Jul 13.
Infections with Acinetobacter baumannii, one of the most troublesome and least studied multidrug-resistant superbugs, are increasing at alarming rates. A. baumannii encodes a type VI secretion system (T6SS), an antibacterial apparatus of Gram-negative bacteria used to kill competitors. Expression of the T6SS varies among different strains of A. baumannii, for which the regulatory mechanisms are unknown. Here, we show that several multidrug-resistant strains of A. baumannii harbor a large, self-transmissible resistance plasmid that carries the negative regulators for T6SS. T6SS activity is silenced in plasmid-containing, antibiotic-resistant cells, while part of the population undergoes frequent plasmid loss and activation of the T6SS. This activation results in T6SS-mediated killing of competing bacteria but renders A. baumannii susceptible to antibiotics. Our data show that a plasmid that has evolved to harbor antibiotic resistance genes plays a role in the differentiation of cells specialized in the elimination of competing bacteria.
鲍曼不动杆菌感染的发生率正以惊人的速度上升,鲍曼不动杆菌是最棘手且研究最少的多重耐药超级细菌之一。鲍曼不动杆菌编码一种VI型分泌系统(T6SS),这是革兰氏阴性菌用于杀死竞争者的抗菌装置。T6SS在不同的鲍曼不动杆菌菌株中的表达有所不同,其调控机制尚不清楚。在这里,我们表明,几种多重耐药的鲍曼不动杆菌菌株携带一个大型的、可自我传递的耐药质粒,该质粒携带T6SS的负调控因子。在含有质粒的抗生素抗性细胞中,T6SS活性被沉默,而部分群体则频繁发生质粒丢失并激活T6SS。这种激活导致T6SS介导的对竞争细菌的杀伤,但使鲍曼不动杆菌易受抗生素影响。我们的数据表明,一个进化后携带抗生素抗性基因的质粒在专门用于消除竞争细菌的细胞分化中发挥作用。