期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：23
页码：7273-7278
DOI：10.1073/pnas.1500553112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceMultidrug-resistant enterococci are leading causes of hospital infection. The antibiotic-perturbed patient gut serves as a staging ground--small numbers of resistant hospital strains colonize and then, greatly amplify in the colon. Little is known of the colonization principles involved--whether hospital strains are competitive or noncompetitive with commensal enterococci or whether mobile elements comprising over 25% of the genome of the former impose significant fitness costs. We unexpectedly found that the prototype vancomycin-resistant Enterococcus faecalis strain V583 was actively killed by fecal organisms, and we traced that to pheromone production by commensal enterococci that trigger lethal mobile element cross-talk. This work highlights the importance of maintaining commensal enterococci in the gut of the hospitalized patient. Multidrug-resistant Enterococcus faecalis possess numerous mobile elements that encode virulence and antibiotic resistance traits as well as new metabolic pathways, often constituting over one-quarter of the genome. It was of interest to determine how this large accretion of mobile elements affects competitive growth in the gastrointestinal (GI) tract consortium. We unexpectedly observed that the prototype clinical isolate strain V583 was actively killed by GI tract flora, whereas commensal enterococci flourished. It was found that killing of V583 resulted from lethal cross-talk between accumulated mobile elements and that this cross-talk was induced by a heptapeptide pheromone produced by native E. faecalis present in the fecal consortium. These results highlight two important aspects of the evolution of multidrug-resistant enterococci: (i) the accretion of mobile elements in E. faecalis V583 renders it incompatible with commensal strains, and (ii) because of this incompatibility, multidrug-resistant strains sharing features found in V583 cannot coexist with commensal strains. The accumulation of mobile elements in hospital isolates of enterococci can include those that are inherently incompatible with native flora, highlighting the importance of maintaining commensal populations as means of preventing colonization and subsequent infection by multidrug-resistant strains.
