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比较分析鲍曼不动杆菌菌株 ATCC 17978 和 AB5075 的蛋白质组学揭示了 II 型分泌系统分泌组在肺部定植和环丙沙星耐药中的差异作用。

Comparative proteomics analyses of Acinetobacter baumannii strains ATCC 17978 and AB5075 reveal the differential role of type II secretion system secretomes in lung colonization and ciprofloxacin resistance.

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.

Clinical Pharmacy Undergraduate Program, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.

出版信息

Microb Pathog. 2019 Mar;128:20-27. doi: 10.1016/j.micpath.2018.12.039. Epub 2018 Dec 20.

Abstract

Acinetobacter baumannii is an emerging nosocomial pathogen with alarming antibiotic resistance profiles. A better understanding of the virulence and resistance mechanisms of this pathogen is necessary for identifying new methods to combat its infections in a more efficient way. In this regard, the type II secretion system (T2SS) of A. baumannii is an attractive target majorly secreting lipid-metabolizing enzymes and contributes significantly to its virulence. No attempts have been made to study the differential role, and the nature of T2SS secreted proteins among different strains of A. baumannii. In this study, we compare T2SS substrates and functions between A. baumannii strains ATCC 17978, and the MDR highly virulent strain AB5075. The functional categories of the T2-secreted proteins were analyzed, and the virulence potential of the tested strains was compared in vivo using a murine pneumonia model. Biofilm formation was compared using crystal violet assay in micro-titer plates. The contribution to antibiotic resistance was measured by determining the minimum inhibitory concentration (MIC) of different classes of antibiotic. Results indicate that the T2SS secretome gives a colonization advantage to AB5075 over ATCC 1797 but is more important for biofilm formation by the latter. Transposon insertional inactivation of the general secretory pathway protein D (gspD), which is a key component in the structure of the T2SS, significantly increased the MIC of AB5075 to ciprofloxacin. Our report is the first to describe the strain-dependent evolution of the T2SS secretome in relation to the virulence and antibiotic resistance attributes of Gram-negative species.

摘要

鲍曼不动杆菌是一种新兴的医院获得性病原体,具有令人震惊的抗生素耐药谱。为了更有效地寻找对抗这种病原体感染的新方法,我们有必要更好地了解其毒力和耐药机制。在这方面,鲍曼不动杆菌的 II 型分泌系统(T2SS)是一个有吸引力的目标,主要分泌脂质代谢酶,对其毒力有重要贡献。尚未有人尝试研究不同鲍曼不动杆菌菌株的 T2SS 分泌蛋白的差异作用和性质。在这项研究中,我们比较了 ATCC 17978 株和 MDR 高毒力株 AB5075 株的 T2SS 底物和功能。分析了 T2 分泌蛋白的功能类别,并在小鼠肺炎模型中比较了测试菌株的毒力潜力。通过结晶紫测定法在微量滴定板中比较了生物膜形成。通过测定不同类别的抗生素的最小抑菌浓度(MIC)来测量对抗生素耐药性的贡献。结果表明,T2SS 分泌组使 AB5075 相对于 ATCC 17978 具有定植优势,但对后者的生物膜形成更为重要。普遍分泌途径蛋白 D(gspD)的转座子插入失活,gspD 是 T2SS 结构的关键组成部分,显著增加了 AB5075 对环丙沙星的 MIC。我们的报告首次描述了与革兰氏阴性菌的毒力和抗生素耐药性相关的 T2SS 分泌组在菌株依赖性方面的演变。

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