Clermont Université, UMR 1071 Inserm/Université d'Auvergne, 63000 Clermont-Ferrand, France.
J Antimicrob Chemother. 2013 Jul;68(7):1558-61. doi: 10.1093/jac/dkt051. Epub 2013 Feb 26.
Bacteria multiresistant to antibiotics are widely supposed to be weakly virulent. However, the virulence traits of carbapenem-resistant Enterobacteriaceae have not been investigated. In this work, we investigated the virulence and resistance mechanism of an extraintestinal pathogenic Escherichia coli (ExPEC) strain (LEB15) that exhibited decreased susceptibility to carbapenems.
The MICs were determined by a microdilution method. The β-lactamase-encoding gene was identified by PCR and sequencing, and the genetic environment was analysed by PFGE and PCR mapping. The genetic background was investigated by multilocus sequence typing (MLST). Virulence-factor-encoding genes and pathogenic islands (PAIs) were detected by multiplex PCR. Virulence was assessed in a mouse sepsis model.
Strain LEB15 produced a chromosomal OXA-48 carbapenemase. The complete bla(OXA-48)-encoding Tn1999.2 transposon was inserted in the LEB15 chromosome. The strain belonged to an MLST cluster of emerging ExPEC strains (ST-127/ST-22). It had a high pathogenic score and eight PAIs (I536, II536, III536, IV536, VI536, I(CFT073), II(CFT073) and II(J96)) and induced an unusually high lethality in the mouse sepsis model.
Strain LEB15 combines both an atypical broad accumulation of virulence factors, which confers a strong killer phenotype, and a decrease in susceptibility to carbapenems following the chromosomal acquisition of bla(OXA-48). This association of virulence and carbapenemase in E. coli strains might pose major problems in the future for E. coli infection management.
人们普遍认为，对抗生素具有多种耐药性的细菌毒力较弱。然而，尚未研究过耐碳青霉烯肠杆菌科的毒力特征。在这项工作中，我们研究了一种表现出对碳青霉烯类药物敏感性降低的肠外致病性大肠杆菌（ExPEC）菌株（LEB15）的毒力和耐药机制。
采用微量稀释法测定 MIC。通过 PCR 和测序鉴定β-内酰胺酶编码基因，并通过 PFGE 和 PCR 图谱分析遗传环境。通过多位点序列分型（MLST）研究遗传背景。通过多重 PCR 检测毒力因子编码基因和致病岛（PAIs）。在小鼠败血症模型中评估毒力。
菌株 LEB15 产生了染色体 OXA-48 碳青霉烯酶。完整的 bla（OXA-48）编码 Tn1999.2 转座子插入 LEB15 染色体中。该菌株属于新兴 ExPEC 菌株（ST-127/ST-22）的 MLST 簇。它具有较高的致病性评分和 8 个 PAI（I536、II536、III536、IV536、VI536、I（CFT073）、II（CFT073）和 II（J96）），并在小鼠败血症模型中引起异常高的致死率。
菌株 LEB15 结合了典型的广泛积累的毒力因子，赋予了强大的杀伤表型，以及在染色体获得 bla（OXA-48）后对碳青霉烯类药物的敏感性降低。这种大肠杆菌菌株毒力和碳青霉烯酶的关联可能在未来对大肠杆菌感染管理构成重大问题。
