Contribution of Type II Topoisomerase Mutations to Fluoroquinolone Resistance in Enterococcus faecium from Japanese Clinical Setting

Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease
Noriko UrushibaraNobumichi Kobayashi

Abstract

High-level fluoroquinolone resistance is conferred by the mutation of conserved serine and acidic amino acids in the quinolone resistance-determining region (QRDR) of the A subunits of the type II topoisomerases, DNA gyrase (GyrA) and topoisomerase IV (ParC). In Japan, fluoroquinolone-resistant Enterococcus faecium continues to emerge in clinical settings. We analyzed 131 Japanese E. faecium clinical isolates for susceptibility to levofloxacin (LVFX), and QRDR mutational status. The bacterial collection had a high percentage of resistance (79%) and showed elevated drug minimal inhibitory concentrations (MICs). Eighty-three isolates had single or combined mutations in gyrA and/or parC; all were resistant to LVFX. A strong correlation was evident between log-transformed MICs and the total number of QRDR mutations (r = 0.7899), confirming the involvement of QRDR mutations in drug resistance, as previously described. Three-dimensional modeling indicated that the amino acid change(s) in QRDR could disrupt the interaction between the enzymes and drugs: the most common cause of quinolone resistance. Interestingly, eight isolates had a single mutation on gyrA and exhibited significantly reduced susceptibility. These data imply that eit...Continue Reading

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Citations

Mar 23, 2021·Journal of Medical Microbiology·Aleksandra TrościańczykBeata Chudzik-Rząd

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Methods Mentioned

BETA
X-ray
nuclear magnetic resonance

Software Mentioned

GraphPad Prism
RAMPAGE
ProSA
UCSF Chimera
Plot
GraphPad

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