Mutations in the , , and genes provide functional insights into the fluoroquinolone-resistant isolated in Vietnam.

INTRODUCTION

has many mechanisms of resistance to fluoroquinolones. The main mechanism is to change the effect of two enzymes that open the DNA helix - the enzyme DNA gyrase () and the topoisomerase IV (). In addition, mutations that render the MexAB-oprM pump () dysfunctional, leading to its overexpression, also enhance resistance to fluoroquinolones. In this study, we aim to detect point mutations of , , and genes that are predicted to be associated with fluoroquinolone resistance in 141 fluoroquinolone-resistant clinical isolates of isolated in Vietnam during 2013-2016.

METHODS

We tested minimum inhibitory concentrations (MICs) of fluoroquinolone antibiotics in 141 clinical isolates of using the VITEK 2 Compact System, followed by PCR assay, to detect and clone the fluoroquinolone resistance-determining region (FRDR) of , , and . Point mutations were analyzed through Sanger sequencing, and the correlation between genetic mutations and phenotypic resistance of 141 clinical isolates was undertaken.

RESULTS

Fluoroquinolone-resistant substitution mutations such as Ile for Thr83 and Met for Thr133 in , Leu for Ser87 in , and Val for Glu126 in the repressor of were mainly detected. Comparative analytical data indicated that amino acid alterations within the and genes are highly associated with resistance to ciprofloxacin (CIP) and levofloxacin (LEV) in the isolates, whereas alterations in the efflux regulatory gene are not highly consistent with resistance in these isolates. Moreover, fluoroquinolone-resistant clinical isolates of were mainly isolated from pus and sputum specimens.

CONCLUSION

In clinical isolates of , a high correlation was observed between MICs of CIP and LEV and alterations in and genes. However, mutations occurring in did not highly correlate with the antibiotic resistance of the bacterium.