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首页> 外文期刊>Infection and immunity >Identification of a Genetic Locus Responsible for Antimicrobial Peptide Resistance in Clostridium difficile
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Identification of a Genetic Locus Responsible for Antimicrobial Peptide Resistance in Clostridium difficile

机译：艰难梭菌中抗菌肽耐药的遗传位点的鉴定。

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Clostridium difficile causes chronic intestinal disease, yet little is understood about how the bacterium interacts with and survives in the host. To colonize the intestine and cause persistent disease, the bacterium must circumvent killing by host innate immune factors, such as cationic antimicrobial peptides (CAMPs). In this study, we investigated the effect of model CAMPs on growth and found that C. difficile is not only sensitive to these compounds but also responds to low levels of CAMPs by expressing genes that lead to CAMP resistance. By plating the bacterium on medium containing the CAMP nisin, we isolated a mutant capable of growing in three times the inhibitory concentration of CAMPs. This mutant also showed increased resistance to the CAMPs gallidermin and polymyxin B, demonstrating tolerance to different types of antimicrobial peptides. We identified the mutated gene responsible for the resistance phenotype as CD1352. This gene encodes a putative orphan histidine kinase that lies adjacent to a predicted ABC transporter operon (CD1349 to CD1351). Transcriptional analysis of the ABC transporter genes revealed that this operon was upregulated in the presence of nisin in wild-type cells and was more highly expressed in the CD1352 mutant. The insertional disruption of the CD1349 gene resulted in significant decreases in resistance to the CAMPs nisin and gallidermin but not polymyxin B. Because of their role in cationic antimicrobial peptide resistance, we propose the designation cprABC for genes CD1349 to CD1351 and cprK for the CD1352 gene. These results provide the first evidence of a C. difficile gene associated with antimicrobial peptide resistance.
机译：艰难梭菌可引起慢性肠道疾病，但对于这种细菌如何与宿主相互作用以及如何在宿主中存活还知之甚少。为了使肠道定居并引起持续性疾病，细菌必须避开宿主先天免疫因子（例如阳离子抗菌肽（CAMP））的杀伤。在这项研究中，我们研究了模型CAMP对生长的影响，发现艰难梭菌不仅对这些化合物敏感，而且通过表达导致CAMP抗性的基因对低水平的CAMP做出反应。通过将细菌接种到含有CAMP乳链菌肽的培养基上，我们分离出了一种能够以抑制浓度CAMP的三倍生长的突变体。此突变体还显示出对CAMPs gallidermin和多粘菌素B的抗性增强，表明对不同类型的抗菌肽具有耐受性。我们鉴定出负责耐药表型的突变基因为CD1352。该基因编码一个推定的孤儿组氨酸激酶，该蛋白与预测的ABC转运蛋白操纵子（CD1349至CD1351）相邻。 ABC转运蛋白基因的转录分析表明，在乳链菌肽存在的条件下，该操纵子在野生型细胞中被上调，并在CD1352突变体中更高表达。 CD1349基因的插入破坏导致对CAMP的乳链菌肽和盖德明而不是多粘菌素B的抵抗力显着降低。由于它们在阳离子抗菌肽抵抗中的作用，我们建议将基因CD1349命名为cprABC至CD1351，将cprK命名为CD1352基因。这些结果提供了艰难梭菌基因与抗菌肽耐药性相关的第一个证据。

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