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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粪肠球菌杆菌肽耐药网络的鉴定和表征

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通讯作者:
E. Lin
E. Lin
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作者:
D. Georgellis;A. S. Lynch;E. Lin

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粪肠球菌对宿主来源的和由肠道微生物的其他细菌产生的抗微生物肽的抗性可能是细菌成功作为肠道寄生虫的重要因素。本研究的目的是确定蛋白质的作用,对模型抗菌肽杆菌肽的耐药性。杆菌肽处理和未处理细胞的蛋白质组分析表明,杆菌肽应激诱导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,鉴定出与已知肽抗生素抗性系统相似的ATP结合盒(ABC)转运蛋白,并显示其介导对杆菌肽的抗性。转运蛋白的表达依赖于一个双组分调节系统和第二个ABC转运蛋白,这是通过基因组分析艾德的。耐药性和调节途径都可以功能性地转移到枯草芽孢杆菌中,证明这些组分对于杆菌肽耐药性的功能和足够性。因此,我们的数据表明,这两个ABC转运蛋白和双组分系统形成了一个针对抗菌肽的耐药网络。粪肠球菌,其中一个转运蛋白作为传感器激活TCS诱导产生第二个转运蛋白,介导实际的阻力。
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.