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首页> 外文期刊>Respiratory Research >Potential mechanisms underlying the acute lung dysfunction and bacterial extrapulmonary dissemination during Burkholderia cenocepacia respiratory infection
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Potential mechanisms underlying the acute lung dysfunction and bacterial extrapulmonary dissemination during Burkholderia cenocepacia respiratory infection

机译：Burkholderia cenocepacia呼吸道感染期间急性肺功能障碍和细菌性肺外扩散的潜在机制

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BackgroundBurkholderia cenocepacia, an opportunistic pathogen that causes lung infections in cystic fibrosis (CF) patients, is associated with rapid and usually fatal lung deterioration due to necrotizing pneumonia and sepsis, a condition known as cepacia syndrome. The key bacterial determinants associated with this poor clinical outcome in CF patients are not clear. In this study, the cytotoxicity and procoagulant activity of B. cenocepacia from the ET-12 lineage, that has been linked to the cepacia syndrome, and four clinical isolates recovered from CF patients with mild clinical courses were analysed in both in vitro and in vivo assays.MethodsB. cenocepacia-infected BEAS-2B epithelial respiratory cells were used to investigate the bacterial cytotoxicity assessed by the flow cytometric detection of cell staining with propidium iodide. Bacteria-induced procoagulant activity in cell cultures was assessed by a colorimetric assay and by the flow cytometric detection of tissue factor (TF)-bearing microparticles in cell culture supernatants. Bronchoalveolar lavage fluids (BALF) from intratracheally infected mice were assessed for bacterial proinflammatory and procoagulant activities as well as for bacterial cytotoxicity, by the detection of released lactate dehydrogenase.ResultsET-12 was significantly more cytotoxic to cell cultures but clinical isolates Cl-2, Cl-3 and Cl-4 exhibited also a cytotoxic profile. ET-12 and CI-2 were similarly able to generate a TF-dependent procoagulant environment in cell culture supernatant and to enhance the release of TF-bearing microparticles from infected cells. In the in vivo assay, all bacterial isolates disseminated from the mice lungs, but Cl-2 and Cl-4 exhibited the highest rates of recovery from mice livers. Interestingly, Cl-2 and Cl-4, together with ET-12, exhibited the highest cytotoxicity. All bacteria were similarly capable of generating a procoagulant and inflammatory environment in animal lungs.ConclusionB. cenocepacia were shown to exhibit cytotoxic and procoagulant activities potentially implicated in bacterial dissemination into the circulation and acute pulmonary decline detected in susceptible CF patients. Improved understanding of the mechanisms accounting for B. cenocepacia-induced clinical decline has the potential to indicate novel therapeutic strategies to be included in the care B. cenocepacia-infected patients.
机译：背景伯克霍尔德氏菌是一种机会性病原体，在囊性纤维化（CF）患者中引起肺部感染，与由于坏死性肺炎和脓毒症（称为cepacia综合征）引起的迅速且通常致命的肺部恶化相关。目前尚不清楚与CF患者临床预后不良相关的关键细菌决定因素。在这项研究中，来自ET-12谱系的cenocepacia的B. cenocepacia的细胞毒性和促凝血活性与cepacia综合征相关联，并在体外和体内分析了从CF患者中分离出的具有临床病程轻的四种临床分离株分析方法B.感染了新概念菌感染的BEAS-2B上皮呼吸细胞，通过流式细胞术检测碘化丙锭染色的细胞来评估细菌的细胞毒性。通过比色测定和流式细胞术检测细胞培养上清液中携带组织因子（TF）的微粒来评估细菌在细胞培养物中诱导的促凝血活性。通过检测释放的乳酸脱氢酶，评估了气管内感染小鼠的支气管肺泡灌洗液（BALF）的细菌促炎和促凝活性以及细菌细胞毒性。结果ET-12对细胞培养物的细胞毒性明显增强，但临床分离株Cl-2， Cl-3和Cl-4也表现出细胞毒性特征。 ET-12和CI-2类似地能够在细胞培养上清液中产生TF依赖的促凝血环境，并增强从感染细胞中释放TF的微粒的释放。在体内测定中，所有细菌分离株均从小鼠肺中传播，但Cl-2和Cl-4表现出从小鼠肝脏中恢复的最高速率。有趣的是，Cl-2和Cl-4以及ET-12表现出最高的细胞毒性。所有细菌在动物肺中都具有相似的能力，可产生促凝和炎性环境。结果表明，洋葱小球藻表现出细胞毒性和促凝血活性，这可能与易感染CF患者的细菌传播进入循环和急性肺功能下降有关。对解释酒渣鼻肠球菌引起的临床下降的机制的更好的理解有可能表明新的治疗策略将被包括在护理感染酒渣鼻球菌的患者中。

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