Identification and Characterization of a Bacitracin Resistance Network in Enterococcus faecalis
Identification and Characterization of a Bacitracin Resistance Network in Enterococcus faecalis
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DOI：
10.1128/aac.02111-13
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发表时间：
2014-03-01
影响因子：
4.9
通讯作者：
Cook, Gregory M.
中科院分区：
文献类型：
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作者：
Gebhard, Susanne;Fang, Chong;Cook, Gregory M.
粪肠球菌对宿主来源和肠道微生物区系其他细菌产生的抗菌肽的耐药性，可能是该细菌作为肠道共生菌成功的一个重要因素。这项研究的目的是确定在模型抗菌肽杆菌肽的抗性中起作用的蛋白质。对杆菌肽处理和未处理细胞的蛋白质组分析表明，杆菌肽胁迫诱导了细胞壁生物合成蛋白的表达，并引起代谢重排。在产量增加的蛋白质中，发现了一种与已知的多肽抗生素耐药系统相似的三磷酸腺苷结合盒(ABC)转运体，并表明它介导了对杆菌肽的耐药性。转运蛋白的表达依赖于一个双组分调控系统和第二个ABC转运蛋白，这是通过基因组分析确定的。抗性和调控途径都可以通过功能转移到枯草芽孢杆菌中，证明了这些成分对杆菌肽抗性的功能和充分性。因此，我们的数据表明，在粪肠球菌中，两个ABC转运体和两个组分系统形成了对抗菌肽的抗性网络，其中一个转运体充当传感器，激活TCS诱导第二个转运体的产生，第二个转运体介导实际的耐药性。
Resistance of Enterococcus faecalis against antimicrobial peptides, both of host origin and produced by other bacteria of the gut microflora, is likely to be an important factor in the bacterium's success as an intestinal commensal. The aim of this study was to identify proteins with a role in resistance against the model antimicrobial peptide bacitracin. Proteome analysis of bacitracin-treated and untreated cells showed that bacitracin stress induced the expression of cell wall-biosynthetic proteins and caused metabolic rearrangements. Among the proteins with increased production, an ATP-binding cassette (ABC) transporter with similarity to known peptide antibiotic resistance systems was identified and shown to mediate resistance against bacitracin. Expression of the transporter was dependent on a two-component regulatory system and a second ABC transporter, which were identified by genome analysis. Both resistance and the regulatory pathway could be functionally transferred to Bacillus subtilis, proving the function and sufficiency of these components for bacitracin resistance. Our data therefore show that the two ABC transporters and the two-component system form a resistance network against antimicrobial peptides in E. faecalis, where one transporter acts as the sensor that activates the TCS to induce production of the second transporter, which mediates the actual resistance.