亚胺培南诱导临床碳青霉烯类耐药鲍曼不动杆菌的孔蛋白、外排泵和碳青霉烯酶基因的转录反应
{"_":"Imipenem-Induced Transcriptional Responses of Porin, Efflux Pumps, and Carbapenemase Genes in Clinical Carbapenem-Resistant .","i":["Acinetobacter baumannii"]}
摘要(中文译文)
耐碳青霉烯类鲍曼不动杆菌（Acinetobacter baumannii）因其能够获得多种耐药机制并在抗生素压力下持续存在，构成严重威胁。本研究旨在通过整合表型、分子、转录及克隆分析，阐明临床分离株对亚胺培南耐药的分子基础。采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）鉴定的11株分离株进行了研究。评估了其对亚胺培南和美罗培南的抗菌药物敏感性，随后通过聚合酶链反应（PCR）检测Ade外排泵、外膜孔蛋白及OXA型碳青霉烯酶基因。利用定量实时PCR评估了亚抑制浓度亚胺培南暴露下的转录反应，并通过任意引物PCR评估了克隆相关性。所有分离株均为碳青霉烯类耐药，所有分离株中均检测到某基因，而有一株分离株中未检测到另一基因。转录分析揭示了分离株对亚胺培南暴露的特异性反应。在Ade外排泵组分中，仅某一组分表现出表达变化，依据分离株不同呈现下调或上调，而其余组分在测试条件下未检测到转录本。外膜孔蛋白基因表现出异质性调控，其中两个基因下调，而部分分离株则显示表达增加。某基因的表达在分离株间存在差异，另一基因的转录本仅在单一分离株中检测到，且暴露后表达降低。克隆分析鉴定出9种不同的基因型，表明遗传多样性且无克隆优势。这些发现凸显了鲍曼不动杆菌碳青霉烯类耐药的多因素和异质性特征，强调了调控性外排机制、孔蛋白调节与碳青霉烯酶携带之间的相互作用。
Abstract
: Carbapenem-resistant poses a critical threat due to its ability to acquire multiple resistance mechanisms and persist under antibiotic pressure. This study aimed to elucidate the molecular basis of imipenem resistance in clinical isolates by integrating phenotypic, molecular, transcriptional, and clonal analyses. : Eleven isolates identified by MALDI-TOF MS (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) were investigated. Antimicrobial susceptibility to imipenem and meropenem was assessed, followed by polymerase chain reaction (PCR) detection of Ade efflux pump, outer membrane porin, and OXA-type carbapenemase genes. Transcriptional responses to sub-inhibitory imipenem exposure were evaluated using quantitative real-time PCR, and clonal relatedness was assessed by arbitrarily primed PCR. : All isolates were carbapenem-resistant, with detected in all isolates and absent in one isolate. Transcriptional analysis revealed isolate-specific responses to imipenem exposure. Among Ade efflux pump components, only exhibited expression changes, displaying either downregulation or upregulation depending on the isolate, whereas , , , and transcripts were not detected under the tested conditions. Outer membrane porin genes showed heterogeneous regulation, with and downregulated, while some isolates showed increased expression. Expression of varied among isolates, and transcripts were detected in a single isolate and were reduced after exposure. Clonal analysis identified nine distinct genotypes, indicating genetic diversity and the absence of clonal dominance. : These findings highlight the multifactorial and heterogeneous nature of carbapenem resistance in , emphasizing the interplay between regulatory efflux mechanisms, porin modulation, and carbapenemase carriage.
如何引用
AMA
Suna Sibel Rizvanoglu, Basar Karaca, Mujde Eryilmaz. {"_":"Imipenem-Induced Transcriptional Responses of Porin, Efflux Pumps, and Carbapenemase Genes in Clinical Carbapenem-Resistant .","i":["Acinetobacter baumannii"]}. Antibiotics (Basel, Switzerland). 2026; doi:10.3390/antibiotics15030299.
APA
Suna Sibel Rizvanoglu, Basar Karaca, Mujde Eryilmaz (2026). {"_":"Imipenem-Induced Transcriptional Responses of Porin, Efflux Pumps, and Carbapenemase Genes in Clinical Carbapenem-Resistant .","i":["Acinetobacter baumannii"]}. Antibiotics (Basel, Switzerland). https://doi.org/10.3390/antibiotics15030299
GB/T 7714
Suna Sibel Rizvanoglu, Basar Karaca, Mujde Eryilmaz. {"_":"Imipenem-Induced Transcriptional Responses of Porin, Efflux Pumps, and Carbapenemase Genes in Clinical Carbapenem-Resistant .","i":["Acinetobacter baumannii"]}[J]. Antibiotics (Basel, Switzerland), 2026 doi:10.3390/antibiotics15030299.
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