Zelinskaya Natalia, Witek Marta A, Conn Graeme L
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA
Antimicrob Agents Chemother. 2015 Dec;59(12):7862-5. doi: 10.1128/AAC.01872-15. Epub 2015 Sep 28.
Chemical modification of 16S rRNA can confer exceptionally high-level resistance to a diverse set of aminoglycoside antibiotics. Here, we show that the pathogen-derived enzyme NpmA possesses dual m(1)A1408/m(1)G1408 activity, an unexpected property apparently unique among the known aminoglycoside resistance 16S rRNA (m(1)A1408) methyltransferases. Although the biological significance of this activity remains to be determined, such mechanistic variation in enzymes acquired by pathogens has significant implications for development of inhibitors of these emerging resistance determinants.
16S rRNA的化学修饰可赋予对多种氨基糖苷类抗生素极高水平的抗性。在此,我们表明病原体来源的酶NpmA具有双重m(1)A1408/m(1)G1408活性,这一意外特性在已知的氨基糖苷类抗性16S rRNA(m(1)A1408)甲基转移酶中显然是独特的。尽管这种活性的生物学意义仍有待确定,但病原体获得的酶的这种机制变异对这些新出现的抗性决定因素的抑制剂开发具有重要意义。