Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer

Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer
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DOI:
10.1073/pnas.1212256110
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发表时间:
2013-04-23
影响因子:
11.1
通讯作者:
Hu, Wei-Shou
Hu, Wei-Shou
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chatterjee, Anushree;Cook, Laura C. C.;Hu, Wei-Shou

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结合是细菌获得抗生素耐药性的最常见方式之一,导致了多重耐药“超级细菌”的出现。“粪肠球菌属的细菌是高度耐药的医院病原体,它们利用接合机制在耐药供体细胞和耐药缺陷受体细胞之间传播抗生素耐药性。在这里,我们报告了一个独特的基于群体感应的通讯系统,该系统使用两个拮抗信号分子来调节四环素抗性质粒pCF 10在大肠杆菌中的接合转移。粪便。受体细胞产生的“配偶感应”肽性信息素被供体细胞检测,以诱导接合遗传转移。使用数学建模和实验,我们表明,第二个拮抗性的“自我感应”的信号肽,以前已知抑制供体细胞的自我诱导,也作为一个经典的群体感应信号的捐助者,其功能是减少在高供体密度的耐药性转移。这种独特的群体感应形式可能提供了一种限制质粒传播的手段,并提供了通过操纵细胞间信号传导来控制耐药性转移的机会,这在临床环境中具有重要意义。
Conjugation is one of the most common ways bacteria acquire antibiotic resistance, contributing to the emergence of multidrug-resistant "superbugs." Bacteria of the genus Enterococcus faecalis are highly antibiotic-resistant nosocomial pathogens that use the mechanism of conjugation to spread antibiotic resistance between resistance-bearing donor cells and resistance-deficient recipient cells. Here, we report a unique quorum sensing-based communication system that uses two antagonistic signaling molecules to regulate conjugative transfer of tetracycline-resistance plasmid pCF10 in E. faecalis. A "mate-sensing" peptide sex pheromone produced by recipient cells is detected by donor cells to induce conjugative genetic transfer. Using mathematical modeling and experimentation, we show that a second antagonistic "self-sensing" signaling peptide, previously known to suppress self-induction of donor cells, also serves as a classic quorum-sensing signal for donors that functions to reduce antibiotic-resistance transfer at high donor density. This unique form of quorum sensing may provide a means of limiting the spread of the plasmid and present opportunities to control antibiotic-resistance transfer through manipulation of intercellular signaling, with implications in the clinical setting.