Efflux Pumps of Gram‐Negative Bacteria: Genetic Responses to Stress and the Modulation of their Activity by pH, Inhibitors, and Phenothiazines

Amaral, Leonard; Fanning, Séamus; Pagès, Jean‐Marie

doi:10.1002/9780470920541.ch2

Cited by 46 publications

(48 citation statements)

References 180 publications

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“…Prior to that, MICs of PA␤N were measured and were found to be Ն300 g/ml for all isolates. On the basis of this, a concentration of 40 g/ml, which is more than 7 times lower than the MIC and which does not inhibit bacterial growth, was chosen (4,33). Antibiotics and PA␤N were purchased from Sigma, Ireland.…”

Section: Methodsmentioning

confidence: 99%

Mechanisms of Fluoroquinolone Resistance in Escherichia coli Isolates from Food-Producing Animals

Karczmarczyk

Martins

Quinn

et al. 2011

Appl Environ Microbiol

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Eleven multidrug-resistant Escherichia coli isolates (comprising 6 porcine and 5 bovine field isolates) displaying fluoroquinolone (FQ) resistance were selected from a collection obtained from the University Veterinary Hospital (Dublin, Ireland). MICs of nalidixic acid and ciprofloxacin were determined by Etest. All showed MICs of nalidixic acid of >256 g/ml and MICs of ciprofloxacin ranging from 4 to >32 g/ml. DNA sequencing was used to identify mutations within the quinolone resistance-determining regions of target genes, and quantitative real-time PCR (qRT-PCR) was used to evaluate the expression of the major porin, OmpF, and component genes of the AcrAB-TolC efflux pump and its associated regulatory loci. Decreased MIC values to nalidixic acid and/or ciprofloxacin were observed in the presence of the efflux pump inhibitor phenylalaninearginine-␤-naphthylamide (PA␤N) in some but not all isolates. Several mutations were identified in genes coding for quinolone target enzymes (3 to 5 mutations per strain). All isolates harbored GyrA amino acid substitutions at positions 83 and 87. Novel GyrA (Asp87 3 Ala), ParC (Ser80 3 Trp), and ParE (Glu460 3 Val) substitutions were observed. The efflux activity of these isolates was evaluated using a semiautomated ethidium bromide (EB) uptake assay. Compared to wild-type E. coli K-12 AG100, isolates accumulated less EB, and in the presence of PA␤N the accumulation of EB increased. Upregulation of the acrB gene, encoding the pump component of the AcrAB-TolC efflux pump, was observed in 5 of 11 isolates, while 10 isolates showed decreased expression of OmpF. This study identified multiple mechanisms that likely contribute to resistance to quinolone-based drugs in the field isolates studied.

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Section: Methodsmentioning

confidence: 99%

Mechanisms of Fluoroquinolone Resistance in Escherichia coli Isolates from Food-Producing Animals

Karczmarczyk

Martins

Quinn

et al. 2011

Appl Environ Microbiol

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“…The question of whether TDR TB infections can be currently cured by an alternative to current ineffective therapy is discussed in this editorial and the supporting evidence that indeed the use of an old neuroleptic phenothiazine drug will most like cure an TDR TB is true for most phenothiazines, inhibits efflux pumps of bacteria [10] and human cells [11] that when over-expressed render these cells multi -drug resistant. Inhibition of these over-expressed efflux pumps reduces or reverses resistance to antibiotics to which the bacterium is initially resistant [12].…”

mentioning

confidence: 99%

Totally Drug Resistant Tuberculosis can be treated with thioridazine in combination with antibiotics to which the patient was initially resistant.

Amaral¹

2012

Biochem & Pharmacol

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“…It all the while expands the bioavailability of different compound and lessens the adequacy of a few medications. Investigations of piperine and piperidine recommend an inhibitory activity against dynamic bacterial efflux pumps, incorporating those in mycobacteria 20 .…”

Section: Efflux Pump Inhibitor Originate From Plantmentioning

confidence: 99%

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2017

IJPSR

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Efflux Pumps of Gram‐Negative Bacteria: Genetic Responses to Stress and the Modulation of their Activity by pH, Inhibitors, and Phenothiazines

Cited by 46 publications

References 180 publications

Mechanisms of Fluoroquinolone Resistance in Escherichia coli Isolates from Food-Producing Animals

Mechanisms of Fluoroquinolone Resistance in Escherichia coli Isolates from Food-Producing Animals

Totally Drug Resistant Tuberculosis can be treated with thioridazine in combination with antibiotics to which the patient was initially resistant.

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