Resistance to fluoroquinolones by the combination of target site mutations and enhanced expression of genes for efflux pumps in Shigella flexneri and Shigella sonnei strains isolated in Korea

Abstract

Among 5938 clinical Shigella spp. isolates, two S. flexneri strains were isolated as those resistant to fluoroquinolones based on the MICs of the following antibiotics: ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin and levofloxacin. S. flexneri 021787 had three substitutions, one in GyrA (Ser83Leu) and two in ParC (Ser80Ile and Arg91Gln). S. flexneri 021895 had four substitutions, two in GyrA (Ser83Leu and Asp87Gly) and two in ParC (Ser80Ile and Arg91Gln). The increased susceptibility of S. flexneri 021787 and S. flexneri 021895 to ciprofloxacin, norfloxacin and ofloxacin in the presence of the uncoupler carbonyl cyamide-m-chlorophenyldrazone implied that energy-dependent active efflux pumps contributed to the resistance against fluoroquinolones. Both S. flexneri 021787 and S. flexneri 021895 were also induced to express tolC (encoding a resistance-nodulation-division transporter), mdfA (encoding a major facilitator superfamily transporter), and ydhE (encoding a multidrug and toxic compound extrusion transporter) in the presence of ciprofloxacin. Thus, these results indicated that chromosome-mediated fluoroquinolone resistance of S. flexneri 021787 and S. flexneri 021895 resulted from the combination of target site mutations and enhanced expression of genes encoding efflux pumps.

Genetic characteristics and changing antimicrobial resistance among Shigella spp. isolated from hospitalized diarrhoeal patients in Kolkata, India

“…During 1999-2003, .60 % of Bangladeshi S. sonnei isolates were resistant to nalidixic acid, but none to ciprofloxacin (Talukder et al, 2006a). In developed countries, although nalidixic acid resistance was common among S. sonnei isolates, the trend of fluoroquinolone resistance is slowly increasing (Kim et al, 2008;Vrints et al, 2009). It is worthwhile mentioning that all S. sonnei isolates in this study were susceptible to ampicillin, which is not used in the treatment of shigellosis in Kolkata.…”

Genomic Portrait of the Evolution and Epidemic Spread of a Recently Emerged Multidrug-Resistant Shigella flexneri Clone in China

“…Resistance genes commonly present in Shigella spp. and Enterobacteriaceae, including the SRL, Tn7, gyrA, dfrA5, bla CTX-M , bla TEM , bla SHV , bla CMY , qnr, qepA, and aac(6=)-Ib-cr, were selected as references (9,(28)(29)(30)(31)) (see Table S1 in the supplemental material). The antibiotic resistance genes were searched using BLASTn, with an E value of 1 ϫ 10 Ϫ15 as the cutoff value for a significant match, based on the data generated by whole-genome sequencing.…”

Genome‐wide transcriptome analysis of fluoroquinolone resistance in clinical isolates of Escherichia coli

“…Another major FQN resistance is chromosomal mutations of DNA gyrase, which is caused by quinolone resistance-determining region modifications. 3,6 It might be interesting to know how quinolone resistance- …”

“…[2][3][4][5][6] In E. coli cells, FQN can be extruded from the outer or inner membrane through the action of various efflux pumps. Previous studies have reported that acrAB, mdfA and norE are involved in FQN resistance.…”

“…The mechanisms of FQN resistance in various bacteria include biofilm formation, overexpression of multidrug efflux pump related genes and chromosomal mutations of DNA gyrase and topoisomerase IV. [2][3][4][5][6] Phage shock protein (psp) response and pilus operons play an important role in acquiring pathogenesis of UTI and biofilm formation in E. coli. [7][8][9] Many investigators are making every effort to overcome FQN resistance by investigating novel mechanisms.…”