Phagocytosis and Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils

Phagocytosis and Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils
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DOI:
10.1093/infdis/jiw001
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发表时间:
2016-05-15
影响因子:
6.4
通讯作者:
DeLeo, Frank R.
DeLeo, Frank R.
中科院分区:
医学2区
文献类型:
--
作者:
Kobayashi, Scott D.;Porter, Adeline R.;DeLeo, Frank R.

文献摘要

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归类为多位点序列类型258(ST 258)的碳青霉烯类耐药肺炎克雷伯菌菌株是最广泛的多重耐药医院获得性病原体之一。由这些生物体引起的感染的治疗是困难的,并且死亡率很高。除了抗生素耐药性之外,ST 258成功的基础仍然不完全确定。在这里,我们测试的假设,ST 258 K。肺炎克雷伯氏菌具有增强的能力来规避人类嗜中性粒细胞的杀伤,这是针对细菌感染的主要细胞防御。人嗜中性粒细胞对ST 258的结合和摄取有限,相应地,对细菌的杀伤有限。另一方面,透射电子显微镜检查显示,任何摄入的微生物在中性粒细胞吞噬体内都容易降解,因此表明中性粒细胞测定中的存活是由于有限的吞噬作用,而不是摄入后的杀微生物剂抗性。我们的研究结果表明,增强中性粒细胞吞噬功能是治疗碳青霉烯类耐药ST 258 K感染的一种潜在治疗方法。肺炎。
Carbapenem-resistant Klebsiella pneumoniae strains classified as multilocus sequence type 258 (ST258) are among the most widespread multidrug-resistant hospital-acquired pathogens. Treatment of infections caused by these organisms is difficult, and mortality is high. The basis for the success of ST258, outside of antibiotic resistance, remains incompletely determined. Here we tested the hypothesis that ST258 K. pneumoniae has enhanced capacity to circumvent killing by human neutrophils, the primary cellular defense against bacterial infections. There was limited binding and uptake of ST258 by human neutrophils, and correspondingly, there was limited killing of bacteria. On the other hand, transmission electron microscopy revealed that any ingested organisms were degraded readily within neutrophil phagosomes, thus indicating that survival in the neutrophil assays is due to limited phagocytosis, rather than to microbicide resistance after uptake. Our findings suggest that enhancing neutrophil phagocytosis is a potential therapeutic approach for treatment of infection caused by carbapenem-resistant ST258 K. pneumoniae.