The AcrAB-TolC Pump Is Involved in Multidrug Resistance in ClinicalShigella flexneriIsolates

Abstract

The two multiple-antibiotic resistance (Mar) phenotypes (n = 8, respectively) and susceptible isolates (n = 4) of Shigella flexneri from China were characterized involving the efflux pump AcrAB-TolC. The accumulation of ciprofloxacin, acrAB-tolC PCR, and levels of mRNA with northern blots were performed in three groups. Sequencing of acrAB-tolC was performed in selected isolates. An efflux inhibition was performed with Phe-Arg-beta-naphthylamide. The accumulation of ciprofloxacin at steady state in susceptible isolates was significantly higher than that in the two Mar groups (p < 0.05). The level of accumulation in the Mar strains was increased upon the addition of the protonophore carbonyl cyanidem-chlorophenylhydrazone. The expression level of acrA mRNA in the Mar isolates was significantly higher than that in the susceptible isolates (p < 0.05). Mar strain H26 had a single-nucleotide substitution in locus 322(G-->T) of acrA, and Mar 0008 in locus 171(C-->A). The susceptible strain N15 had a base deletion in locus 36 (C) of tolC gene. The role of the inhibitors of efflux pumps was significant in some isolates with the high expression of Mar pump genes. In conclusion, overexpression of acrA gene leads to Mar in clinical isolates of S. flexneri, and ciprofloxacin acquired susceptible to S. flexneri with Phe-Arg-beta-naphthylamide.

Antimicrobial susceptibility and mechanism of resistance in Shigella isolates from rural China

“…suggesting that the AcrAB-TolC efflux system is vital in multi-drug resistance in Shigella spp., and a similar study observed deletion in locus 36 (C) of the tolC gene. The rate of mutation in gene acrA was also observed anda similar study revealed that had a single nucleotide substitution in locus 322 (G toT) and in locus 171 (C toA) of acrA gene (Yang et al 2008). …”

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

“…For Shigella flexneri, the involvement of efflux, including AcrAB overproduction, leading to high-level resistance to fluoroquinolones, was reported (326,327). Inactivation of the MFS pump MdfA-encoding gene led to an 8-fold decease in the norfloxacin MIC (328).…”

Multidrug resistance in hydrocarbon-tolerant Gram-positive and Gram-negative bacteria

“…AcrB of Escherichia coli is the best studied member of the HAE1 family (Poole, 2001;Pos, 2009). Homologues of acrAB are apparently widespread among Gram-negative bacteria and were found in various genera (Nikaido, 1996;Nikaido and Zgurskaya, 2001;Poole, 2005;Singh et al, 2010;Yang et al, 2008).…”