外膜囊泡 (OMVs)介导的鲍曼不动杆菌碳青霉烯酶基因新传播机制研究

In the last decade, the increasing recovery of Carbapenem-resistant Acinetobacter baumannii in the clinic, which has caused more treatment failures and brought big challenge to clinician, is a frightening reality. Acinetobacter baumannii develops resistance to carbapenem rapidly due to its robust ability to acquire carbapenemase-encoding genes in this organism, but this ability cannot be explained by mobile elements. Outer Membrane Vesicles (OMVs) have been confirmed as a novel mechanism of the dissemination of resistance genes among bacteria, but the role of these OMVs in acquiring carbapenemase genes in A. baumannii is still unclear. In this study, we will compare the production, function and ability of transferring carbapenemase genes of OMVs between different species and clones of Acinetobacter spp., by performing the transmission electron microscopy, content determining assay, molecular hybridization, transfer experiments and analyzing bioinformatic data of the clinical Acinetobacter spp. collected in our lab, to confirm the role of OMVs in the dissemination of carbapenemase genes in A. baumannii. This project will provide scientific basis for development of prevention, control and treatment strategy against A. baumannii infections and bring new method for studying the evolution mechanism of this multidrug-resistant organism.

碳青霉烯耐药鲍曼不动杆菌在全世界范围内分离率的快速上升，给临床抗感染治疗带来极大的困难。鲍曼不动杆菌对碳青霉烯类抗生素迅速产生耐药的主要原因是其具备强大的获得外源碳青霉烯酶基因的能力，但现有移动元件不能很好解释其如何迅速获得大量耐药基因。外膜囊泡（Outer Membrane Vesicles，OMVs）已被证实是介导耐药基因细菌间传播的新机制，但目前OMVs在鲍曼不动杆菌碳青霉烯酶基因获得及传播中的作用尚不明确。本研究拟利用课题组已有临床分离不动杆菌菌株库资源，结合前期获得的分子分型、耐药机制信息数据，采用电镜观察、内容物含量测定、分子杂交、转化试验等实验手段，系统比较不动杆菌不同种、不同克隆所产生的OMVs的数量和功能的差异，明确OMVs在鲍曼不动杆菌碳青霉烯酶基因传播中的作用。课题的实施将为多重耐药鲍曼不动杆菌耐药进化研究提供新的思路，为鲍曼不动杆菌耐药控制策略制定提供新的科学依据。

近年来，鲍曼不动杆菌作为最常见的院内感染致病菌，给临床带来了极大挑战。在鲍曼不动杆菌中，外膜囊泡（Outer Membrane Vesicles，OMVs）已被证实是介导耐药基因细菌间传播的新机制。本研究利用课题组已有临床分离不动杆菌菌株库资源，结合前期获得的分子分型、耐药机制信息数据，通过透射电镜观察、内容物含量测定、分子杂交、转化试验等实验手段，比较了不同种、不同克隆不动杆菌的OMV产生能力、功能及碳青霉烯耐药基因转化能力。结果证实OMV可以作为blaOXA-24、blaOXA-23 、blaNDM-1等耐药基因及质粒的传播机制。并且在MDR-AB流行克隆中，OMV产量高且介导的转化效率高。OMV介导质粒转播的机制及多重耐药鲍曼不动杆菌OMV生物合成的影响因素需要进一步试验证实。本研究明确了OMV在多重耐药鲍曼不动杆菌耐药基因传播的中的作用，同时为多重耐药鲍曼不动杆菌疫苗研制和治疗策略制定提供新的思路。