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首页> 外文期刊>Infection and immunity >New Role for Human α-Defensin 5 in the Fight against Hypervirulent Clostridium difficile Strains
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New Role for Human α-Defensin 5 in the Fight against Hypervirulent Clostridium difficile Strains

机译：人α-防御素5在抗高毒艰难梭菌菌株中的新作用

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Clostridium difficile infection (CDI), one of the most common hospital-acquired infections, is increasing in incidence and severity with the emergence and diffusion of hypervirulent strains. CDI is precipitated by antibiotic treatment that destroys the equilibrium of the gut microbiota. Human α-defensin 5 (HD5), the most abundant enteric antimicrobial peptide, is a key regulator of gut microbiota homeostasis, yet it is still unknown if C. difficile, which successfully evades killing by other host microbicidal peptides, is susceptible to HD5. We evaluated, by means of viability assay, fluorescence-activated cell sorter (FACS) analysis, and electron microscopy, the antimicrobial activities of α-defensins 1 and 5 against a panel of C. difficile strains encompassing the most prevalent epidemic and hypervirulent PCR ribotypes in Europe (012, 014/020, 106, 018, 027, and 078). Here we show that (i) concentrations of HD5 within the intestinal physiological range produced massive C. difficile cell killing; (ii) HD5 bactericidal activity was mediated by membrane depolarization and bacterial fragmentation with a pattern of damage peculiar to C. difficile bacilli, compared to commensals like Escherichia coli and Enterococcus faecalis; and (iii) unexpectedly, hypervirulent ribotypes were among the most susceptible to both defensins. These results support the notion that HD5, naturally present at very high concentrations in the mucosa of the small intestine, could indeed control the very early steps of CDI by killing C. difficile bacilli at their germination site. As a consequence, HD5 can be regarded as a good candidate for the containment of hypervirulent C. difficile strains, and it could be exploited in the therapy of CDI and relapsing C. difficile-associated disease.
机译：艰难梭菌感染（CDI）是最常见的医院获得性感染之一，随着高毒力菌株的出现和扩散，其发病率和严重性也在增加。 CDI通过抗生素处理而沉淀，破坏了肠道菌群的平衡。人α-防御素5（HD5）是最丰富的肠溶抗菌肽，是肠道菌群稳态的关键调节剂，但仍难以确定成功避开其他宿主杀微生物肽杀伤力的艰难梭菌是否对HD5敏感。我们通过生存力测定，荧光激活细胞分选仪（FACS）分析和电子显微镜评估了α-防御素1和5对一组艰难梭菌菌株的抗菌活性，其中所述菌株包括最流行的流行和高毒PCR核糖型在欧洲（012、014 / 020、106、018、027和078）。在这里，我们显示（i）肠道生理范围内的HD5浓度会导致大量艰难梭菌杀伤; （ii）与诸如大肠杆菌和粪肠球菌相比，HD5杀菌活性是由膜去极化和细菌破碎介导的，具有艰难梭菌特有的损害模式; （iii）出乎意料的是，高毒力核糖型最容易受到两种防御素的攻击。这些结果支持这样的观念，即以高浓度天然存在于小肠粘膜中的HD5确实可以通过杀死艰难梭菌芽孢杆菌的发芽部位来控制CDI的早期步骤。结果，HD5可以被认为是遏制高毒性艰难梭菌菌株的良好候选者，并且可以用于治疗CDI和复发性艰难梭菌相关疾病。

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