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Instability of the 16S rRNA methyltransferase-encoding npmA gene: why have bacterial cells possessing npmA not spread despite their high and broad resistance to aminoglycosides?
The Journal of Antibiotics ( IF 3.3 ) Pub Date : 2018-Sep-01 , DOI: 10.1038/s41429-018-0070-y
Yoshimasa Ishizaki , Yuko Shibuya , Chigusa Hayashi , Kunio Inoue , Teruo Kirikae , Tatsuya Tada , Tohru Miyoshi-Akiyama , Masayuki Igarashi

The NpmA bacterial 16S rRNA methyltransferase, which is identified from Escherichia coli strains, confers high resistance to many types of aminoglycoside upon its host cells. But despite its resistance-conferring ability, only two cases of its isolation from E. coli (14 years apart) have been reported to date. Here, we investigated the effect of the npmA gene on aminoglycoside resistance in Pseudomonas aeruginosa and Klebsiella pneumoniae and its stability in E. coli cells by comparing it with armA, another 16S rRNA methyltransferase gene currently spreading globally. As a result, we found that npmA conferred resistance to all types of aminoglycoside antibiotics we tested (except streptomycin) in both P. aeruginosa and K. pneumoniae, as well in E. coli. In addition, co-expression of armA and npmA resulted in an additive effect for the resistance. However, in return for the resistance, we also observed that the growth rates and the cell survivability of the strains transformed with the npmA-harboring plasmids were inferior than those of the control strains and that these plasmids were easily disrupted by IS10, IS1, and IS5 insertion sequences. We discuss these data in the context of the threat posed by pathogenic strains possessing npmA.

中文翻译:

编码16S rRNA甲基转移酶的npmA基因的不稳定性:尽管具有npmA的细菌细胞对氨基糖苷类药物具有高度和广泛的抗性,但为什么它们仍不扩散?

从大肠杆菌菌株中鉴定出的NpmA细菌16S rRNA甲基转移酶对宿主细胞的许多类型的氨基糖苷具有很高的抗性。但是,尽管它具有赋予抗药性的能力,但迄今仅报道了两起与大肠杆菌分离的病例(相距14年)。在这里,我们通过与目前正在全球范围内传播的另一种16S rRNA甲基转移酶armA进行比较,研究了npmA基因对铜绿假单胞菌和肺炎克雷伯菌的氨基糖苷抗性的影响及其在大肠杆菌细胞中的稳定性。结果,我们发现npmA赋予了我们在铜绿假单胞菌和肺炎克雷伯氏菌以及大肠杆菌中测试的所有类型的氨基糖苷抗生素(链霉素除外)耐药性。此外,armA和npmA的共表达导致抗性的累加效应。然而,作为抗药性的回报,我们还观察到,用npmA-harboring质粒转化的菌株的生长速率和细胞存活率均低于对照菌株,并且这些质粒容易被IS10,IS1和IS10破坏。 IS5插入序列。我们在拥有npmA的致病菌株所构成的威胁的背景下讨论这些数据。
更新日期:2018-06-08
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