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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Relationship of agr expression and function with virulence and vancomycin treatment outcomes in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.
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Relationship of agr expression and function with virulence and vancomycin treatment outcomes in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

机译：耐甲氧西林金黄色葡萄球菌引起的实验性心内膜炎中agr表达和功能与毒力和万古霉素治疗结果的关系。

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The accessory gene regulator (agr) locus has been shown to be important for virulence in several animal models of Staphylococcus aureus infection. However, the role of agr in human infections, and specifically in antibiotic treatment, is controversial. Interestingly, agr dysfunction has been associated with reduced vancomycin responses. To systematically investigate the role of agr in virulence and treatment outcome in the context of endovascular infection, 10 well-characterized vancomycin-susceptible methicillin-resistant S. aureus (MRSA) bloodstream isolates (5 agr-I [clonal complex 45, or CC45] and 5 agr-II [CC5]) were studied for (i) agr function, (ii) RNAIII transcriptional profiles, (iii) agr locus sequences, (iv) intrinsic virulence and responses to vancomycin therapy in an experimental infective endocarditis (IE) model, and (v) in vivo RNAIII expression. Significant differences in agr function (determined by delta-hemolysin activity) correlated with the time point of RNAIII transcription (earlier RNAIII onset equals increased agr function). Unexpectedly, four MRSA strains with strong delta-hemolysin activities exhibited significant resistance to vancomycin treatment in experimental IE. In contrast, five of six MRSA strains with weak or no delta-hemolysin activity were highly susceptible to vancomycin therapy in the IE model. agr sequence analyses showed no common single-nucleotide polymorphism predictive of agr functionality. In vivo RNAIII expression in cardiac vegetations did not correlate with virulence or vancomycin treatment outcomes in the IE model. Inactivation of agr in two strains with strong delta-hemolysin activity did not affect virulence or the in vivo efficacy of vancomycin. Our findings suggest that agr dysfunction does not correlate with vancomycin treatment failures in this experimental IE model in two distinct MRSA genetic backgrounds.
机译：在几种金黄色葡萄球菌感染的动物模型中，辅助基因调节物（agr）基因座已显示对毒力很重要。然而，农杆菌在人类感染中的作用，特别是在抗生素治疗中的作用，是有争议的。有趣的是，农业功能障碍与万古霉素反应降低有关。为了系统地研究agr在血管内感染的情况下在毒力和治疗结果中的作用，研究了10个特征明确的对万古霉素敏感的耐甲氧西林金黄色葡萄球菌（MRSA）血流分离株（5个agr-1（克隆复合物45，或CC45）和5种agr-II [CC5]）在实验性感染性心内膜炎（IE）中研究了（i）agr功能，（ii）RNAIII转录谱，（iii）agr基因座序列，（iv）内在毒力和对万古霉素治疗的反应（v）体内RNAIII表达。 agr功能的显着差异（由δ-溶血素活性决定）与RNAIII转录的时间点相关（RNAIII较早发作等于增加的agr功能）。出乎意料的是，在实验性IE中，四种具有强δ-溶血素活性的MRSA菌株对万古霉素治疗表现出显着的抗性。相比之下，在IE模型中，六种MRSA菌株中有五种具有弱溶血素或溶血素-溶血素的活性对万古霉素治疗高度敏感。 agr序列分析显示没有常见的单核苷酸多态性可预测agr功能。 IE模型中，心脏植被中的体内RNAIII表达与毒力或万古霉素治疗结果无关。在具有强δ-溶血素活性的两种菌株中，agr的失活不会影响万古霉素的毒力或体内功效。我们的发现表明，在两个不同的MRSA遗传背景下，该实验性IE模型中的agr功能障碍与万古霉素治疗失败无关。

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