title: Efflux as a mechanism of antimicrobial drug resistance in clinical relevant microorganisms: the role of efflux inhibitors.
abstract: Microbial resistance against antibiotics is a serious threat to the effective treatment of infectious diseases. Several mechanisms exist through which microorganisms can develop resistance against antimicrobial drugs, of which the overexpression of genes to produce efflux pumps is a major concern. Several efflux transporters have been identified in microorganisms, which infer resistance against specific antibiotics and even multidrug resistance. Areas covered: This paper focuses on microbial resistance against antibiotics by means of the mechanism of efflux and gives a critical overview of studies conducted to overcome this problem by combining efflux pump inhibitors with antibiotics. Information was obtained from a literature search done with MEDLINE, Pubmed, Scopus, ScienceDirect, OneSearch and EBSCO host. Expert opinion: Efflux as a mechanism of multidrug resistance has presented a platform for improved efficacy against resistant microorganisms by co-administration of efflux pump inhibitors with antimicrobial agents. Although proof of concept has been shown for this approach with in vitro experiments, further research is needed to develop more potent inhibitors with low toxicity which is clinically effective.
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Willers
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Johannes Frederik
authors.initials: JF
authors.lastname: Wentzel
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Lissinda Hester
authors.initials: LH
authors.lastname: du Plessis
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Chrisna
authors.initials: C
authors.lastname: Gouws
authors.affiliation: a Centre of Excellence for Pharmaceutical Sciences , North-West University , Potchefstroom , South Africa.
authors.forename: Josias Hendrik
authors.initials: JH
authors.lastname: Hamman
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000235:genetics; D003141:Communicable Diseases / Q000188:drug therapy* / Q000382:microbiology; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D026901:Membrane Transport Proteins
keywords: Antimicrobial drug resistant; efflux pump inhibition; efflux transporters; multidrug resistance