Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations.
Biochem Biophys Res Commun
; 453(2): 254-67, 2014 Oct 17.
Article
em En
| MEDLINE
| ID: mdl-24878531
ABSTRACT
Multidrug resistance (MDR) refers to the capability of bacterial pathogens to withstand lethal doses of structurally diverse drugs which are capable of eradicating non-resistant strains. MDR has been identified as a major threat to the public health of human being by the World Health Organization (WHO). Among the four general mechanisms that cause antibiotic resistance including target alteration, drug inactivation, decreased permeability and increased efflux, drug extrusion by the multidrug efflux pumps serves as an important mechanism of MDR. Efflux pumps not only can expel a broad range of antibiotics owing to their poly-substrate specificity, but also drive the acquisition of additional resistance mechanisms by lowering intracellular antibiotic concentration and promoting mutation accumulation. Over-expression of multidrug efflux pumps have been increasingly found to be associated with clinically relevant drug resistance. On the other hand, accumulating evidence has suggested that efflux pumps also have physiological functions in bacteria and their expression is subject tight regulation in response to various of environmental and physiological signals. A comprehensive understanding of the mechanisms of drug extrusion, and regulation and physiological functions of efflux pumps is essential for the development of anti-resistance interventions. In this review, we summarize the development of these research areas in the recent decades and present the pharmacological exploitation of efflux pump inhibitors as a promising anti-drug resistance intervention.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Bactérias
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Farmacorresistência Bacteriana Múltipla
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article