Altered Outer Membrane Transcriptome Balance with AmpC Overexpression in Carbapenem-Resistant Enterobacter cloacae.
Altered Outer Membrane Transcriptome Balance with AmpC Overexpression in Carbapenem-Resistant Enterobacter cloacae.
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DOI：
10.3389/fmicb.2016.02054
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发表时间：
2016
影响因子：
5.2
通讯作者：
Tryniszewska E
中科院分区：
文献类型：
--
作者：
Majewski P;Wieczorek P;Ojdana D;Sieńko A;Kowalczuk O;Sacha P;Nikliński J;Tryniszewska E
多药耐药(MDR)细菌的发病率不断上升是现代医学面临的一个新挑战。碳青霉烯类药物被认为是治疗多药耐药病原体引起的感染的“最后一线”药物，但由于各种耐药机制的发病率不断增加，其用途正在减少。阴沟肠杆菌最近开始成为一种容易表现出多重耐药的重要病原菌。本研究旨在探讨44株阴沟肠杆菌对至少一种碳青霉烯类抗生素耐药的分子基础，以及21株敏感菌株对碳青霉烯类抗生素耐药的分子基础。对65株阴沟肠杆菌临床分离株进行了定量聚合酶链式反应(QPCR)，扩增AmpC、OmpF和OMPC转录本，并对MLST方案中包含的等位基因进行核苷酸序列分析。据报道，三种不同的碳青霉烯类耐药机制共同作用--产生OXA-48(5%)，过度产生AmpC酶(97.7%)，以及改变外膜(OM)转录组平衡。耐碳青霉烯类阴沟肠杆菌的特征为(1.)OmpF基因下调(53.4%)，该基因编码具有广泛跨膜通道的蛋白质；OM转录组平衡(79.1%)偏向于OMPC基因，编码最近报道的具有限制性跨膜通道的蛋白。碳青霉烯类敏感菌株的亚群表现出相对较高的序列多样性，没有优势类型。在碳青霉烯类耐药株中，ST-89明显占优势(88.6%)，表明耐药株呈克隆性传播。越来越多的病原体对目前所有可用的抗菌剂产生抗药性，这预示着未来“后抗生素时代”的潜在风险。需要作出巨大努力来探索抗菌素对“最后手段”产生抗药性的背景。
The growing incidence of multidrug-resistant (MDR) bacteria is an emerging challenge in modern medicine. The utility of carbapenems, considered “last-line” agents in therapy of infections caused by MDR pathogens, is being diminished by the growing incidence of various resistance mechanisms. Enterobacter cloacae have lately begun to emerge as an important pathogen prone to exhibiting multiple drug resistance. We aimed to investigate the molecular basis of carbapenem-resistance in 44 E. cloacae clinical strains resistant to at least one carbapenem, and 21 susceptible strains. Molecular investigation of 65 E. cloacae clinical strains was based on quantitative polymerase chain reaction (qPCR) allowing for amplification of ampC, ompF, and ompC transcripts, and analysis of nucleotide sequences of alleles included in MLST scheme. Co-operation of three distinct carbapenem resistance mechanisms has been reported—production of OXA-48 (5%), AmpC overproduction (97.7%), and alterations in outer membrane (OM) transcriptome balance. Carbapenem-resistant E. cloacae were characterized by (1.) downregulation of ompF gene (53.4%), which encodes protein with extensive transmembrane channels, and (2.) the polarization of OM transcriptome-balance (79.1%), which was sloped toward ompC gene, encoding proteins recently reported to possess restrictive transmembrane channels. Subpopulations of carbapenem-susceptible strains showed relatively high degrees of sequence diversity without predominant types. ST-89 clearly dominates among carbapenem-resistant strains (88.6%) suggesting clonal spread of resistant strains. The growing prevalence of pathogens resistant to all currently available antimicrobial agents heralds the potential risk of a future “post-antibiotic era.” Great efforts need to be taken to explore the background of resistance to “last resort” antimicrobials.