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Inactivation of Mgrb Gene Regulator and Resistance to Colistin is Becoming Endemic in Carbapenem-Resistant Klebsiella Pneumoniae in Greece: A Nationwide Study from 2014 to 2017.

AIDS research and human retroviruses(2020)SCI 4区

Aix Marseille Univ | Natl & Kapodistrian Univ Athens | Univ Hosp Larissa | Thriasio Gen Hosp | KAT Gen Hosp | Sismanogleio Gen Hosp | Univ Hosp | Iaso Matern & Gynecol Hosp | Evagelismos Gen Hosp

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Abstract
INTRODUCTION:In Greece, the spread of carbapenem-resistant Enterobacteriaceae in humans has led to the reintroduction of colistin as a therapeutic agent. Unfortunately, colistin resistance with different mechanisms has emerged. The present work aims to determine the prevalence of carbapenem and colistin resistance and the corresponding mechanisms in Klebsiella pneumoniae clinical isolates from Greece.METHODS:From 2014 to 2017, 288 carbapenem-resistant K. pneumoniae clinical strains were gathered from a collection of 973 isolates from eight different hospitals in Greece. Antibiotic susceptibility testing was performed using three different methods. Screening of carbapenem and colistin resistance genes was conducted using polymerase chain reaction (PCR) amplification and sequencing.RESULTS:Among the 288 (29.6 %) carbapenem-resistant isolates, 213 (73.9%) were colistin-resistant (minimum inhibitory concentration [MIC] >2 mg/L). The KPC type was the most common carbapenemase gene (116; 40.3%), followed by VIM (41; 14.2%), NDM (33; 11.5%) and OXA-48 (22; 7.6%). Moreover, 44 (15.3%) strains co-produced two types of carbapenemases. No mcr genes were detected for colistin resistance but mutations in chromosomal genes were found. These included inactivation of the mgrB gene for 148 (69.5%) strains, including insertion sequences for 94 (44.1%), nonsense mutations for 4 (1.9%) and missense mutations for 24 (11.3%). Moreover, PCR amplification of mgrB gene was negative for 26 (12.2%) strains. Finally, 65 (30.5%) colistin-resistant strains exhibited a wild-type mgrB, the mechanisms of which remain to be elucidated.CONCLUSION:This study shows that K. pneumoniae clinical strains in Greece are resistant to both carbapenems and colistin and this is endemic and is likely chromosomally encoded.
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Klebsiella pneumoniae,Greece,carbapenems,colistin resistance,mgrB gene
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要点】:在希腊,碳青霉烯类耐药肺炎克雷伯菌对粘菌素耐药性日益普遍,本研究发现 mgrB 基因调节因子失活是主要的耐药机制,且存在染色体编码的耐药性。

方法】:通过聚合酶链反应(PCR)扩增和测序,对2014至2017年间来自希腊八所医院的288株碳青霉烯类耐药肺炎克雷伯菌临床分离株进行抗生素敏感性测试和耐药基因筛查。

实验】:实验收集了288株碳青霉烯类耐药肺炎克雷伯菌临床分离株,发现其中213株对粘菌素耐药,主要通过 mgrB 基因失活(包括插入序列、无义突变和错义突变)实现,无 mcr 基因检测到,且部分菌株表现出野生型 mgrB 基因但耐药机制尚未明确。