Fitness cost and interference of Arm/Rmt aminoglycoside resistance with the RsmF housekeeping methyltransferases.

Antimicrobial Agents and Chemotherapy
Belen GutierrezBruno Gonzalez-Zorn

Abstract

Arm/Rmt methyltransferases have emerged recently in pathogenic bacteria as enzymes that confer high-level resistance to 4,6-disubstituted aminoglycosides through methylation of the G1405 residue in the 16S rRNA (like ArmA and RmtA to -E). In prokaryotes, nucleotide methylations are the most common type of rRNA modification, and they are introduced posttranscriptionally by a variety of site-specific housekeeping enzymes to optimize ribosomal function. Here we show that while the aminoglycoside resistance methyltransferase RmtC methylates G1405, it impedes methylation of the housekeeping methyltransferase RsmF at position C1407, a nucleotide that, like G1405, forms part of the aminoglycoside binding pocket of the 16S rRNA. To understand the origin and consequences of this phenomenon, we constructed a series of in-frame knockout and knock-in mutants of Escherichia coli, corresponding to the genotypes rsmF(+), ΔrsmF, rsmF(+) rmtC(+), and ΔrsmF rmtC(+). When analyzed for the antimicrobial resistance pattern, the ΔrsmF bacteria had a decreased susceptibility to aminoglycosides, including 4,6- and 4,5-deoxystreptamine aminoglycosides, showing that the housekeeping methylation at C1407 is involved in intrinsic aminoglycoside susceptibi...Continue Reading

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Citations

Aug 18, 2016·Journal of Global Antimicrobial Resistance·Bingming OuGuoqiang Zhu
Dec 17, 2014·Biochimie·O V SergeevaP V Sergiev
Feb 19, 2015·Antimicrobial Agents and Chemotherapy·Antonio CannatelliGian Maria Rossolini
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Jan 12, 2017·The Journal of Antimicrobial Chemotherapy·C M OvejeroB Gonzalez-Zorn
Jul 29, 2020·The Journal of Antimicrobial Chemotherapy·Lorena Rodríguez-RubioBruno Gonzalez-Zorn
Mar 17, 2020·Frontiers in Genetics·Philipp PletnevPetr V Sergiev
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Oct 5, 2020·Infectious Disease Clinics of North America·Jun-Ichi WachinoYoshichika Arakawa
Jul 14, 2018·Microbiology Spectrum·Laurent PoirelStefan Schwarz

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