外排泵的作用：MexAB - OprM和MexXY（- OprA）、AmpC头孢菌素酶及OprD孔蛋白在从囊性纤维化患者和烧伤患者中分离出的非产金属β - 内酰胺酶铜绿假单胞菌中的作用
Role of efflux pumps: MexAB-OprM and MexXY(-OprA), AmpC cephalosporinase and OprD porin in non-metallo-β-lactamase producing Pseudomonas aeruginosa isolated from cystic fibrosis and burn patients.
作者信息
Aghazadeh Mohammad, Hojabri Zoya, Mahdian Reza, Nahaei Mohammad Reza, Rahmati Marveh, Hojabri Tina, Pirzadeh Tahereh, Pajand Omid
机构信息
Tabriz Research Center of Infectious and Tropical Diseases, Tabriz University of Medical Sciences, Tabriz, Iran.
Tabriz Research Center of Infectious and Tropical Diseases, Tabriz University of Medical Sciences, Tabriz, Iran; Microbiology Department, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
出版信息
Infect Genet Evol. 2014 Jun;24:187-92. doi: 10.1016/j.meegid.2014.03.018. Epub 2014 Mar 30.
PURPOSE OF THE RESEARCH
In order to gain a better understanding of the role of several mechanisms in antibiotic resistance in Pseudomonas aeruginosa clinical isolates obtained from CF and burn patients, we evaluated gene expression of efflux pumps MexAB-OprM and MexXY(-OprA), the natural β-lactamase AmpC and outer membrane porin protein OprD. Also, the presence of genes encoding Ambler classes A, B β-lactamases and aminoglycoside modifying enzymes (AMEs) was examined.
PRINCIPAL RESULTS
Piperacillin-tazobactam and amikacin retained the highest in vitro activities among 21 CF and 27 burn P. aeruginosa isolates. Based on Enterobacterial Repetitive Intergenic Consensus (ERIC) PCR, 15 distinct patterns were detected. There were 5 CF and 6 burn isolates harbored PER-1 and VEB-1, respectively. Among AMEs, involved in resistance of anti-Pseudomonas aminoglycosides, aac(6')-Ib was the most prevalent gene. Among CF isolates, mexA overexpression was the most prevalent mechanism (47.6%) followed by mexX (42.8%), ampC (9.5%) and oprD downregulation (4.7%). Among burn isolates, the prevalence of mexX, mexA, and ampC overexpression was 62.9%, 74%, and 11.1%, respectively. Downregulation of oprD was observed in 14.8% of burn isolates.
MAJOR CONCLUSIONS
Among CF isolates, mexX and mexA overexpression were the major contributing factors to aminoglycoside (gentamicin) and carbapenem (meropenem) resistance, respectively while among burn isolates, AMEs in conjunction with mexX hyperexpression were identified to be responsible for aminoglycoside resistance. Also mexA overexpression was partially associated with carbapenem resistance. Moreover, cephalosporin resistance was linked to overexpression of mexA and/or mexX. The impact of interplay between different resistance mechanisms on resistant phenotypes was more complicated among burn than CF isolates.
研究目的
为了更好地了解多种机制在从囊性纤维化（CF）患者和烧伤患者中分离出的铜绿假单胞菌临床菌株抗生素耐药性中的作用，我们评估了外排泵MexAB - OprM和MexXY（-OprA）、天然β-内酰胺酶AmpC以及外膜孔蛋白OprD的基因表达。此外，还检测了编码Ambler A类、B类β-内酰胺酶和氨基糖苷修饰酶（AMEs）的基因的存在情况。
主要结果
在21株CF和27株烧伤铜绿假单胞菌分离株中，哌拉西林-他唑巴坦和阿米卡星保持了最高的体外活性。基于肠杆菌重复基因间共识（ERIC）PCR，检测到15种不同的模式。分别有5株CF分离株和6株烧伤分离株携带PER - 1和VEB - 1。在参与抗假单胞菌氨基糖苷类耐药的AMEs中，aac(6')-Ib是最普遍的基因。在CF分离株中，mexA过表达是最普遍的机制（47.6%），其次是mexX（42.8%）、ampC（9.5%）和oprD下调（4.7%）。在烧伤分离株中，mexX、mexA和ampC过表达的发生率分别为62.9%、74%和11.1%。在14.8%的烧伤分离株中观察到oprD下调。
主要结论
在CF分离株中，mexX和mexA过表达分别是对氨基糖苷类（庆大霉素）和碳青霉烯类（美罗培南）耐药的主要促成因素，而在烧伤分离株中，AMEs与mexX过表达共同导致氨基糖苷类耐药。此外，mexA过表达与碳青霉烯类耐药部分相关。此外，头孢菌素耐药与mexA和/或mexX过表达有关。不同耐药机制之间的相互作用对耐药表型的影响在烧伤分离株中比在CF分离株中更复杂。
Zotero 插件