Antimicrobial resistance is a current major challenge in chemotherapy and infection control. The ability of bacterial and eukaryotic cells to recognize and pump toxic compounds from within the cell to the environment before they reach their targets is one of the important mechanisms contributing to this phenomenon. Drug efflux pumps are membrane transport proteins that require energy to export substrates and can be selective for a specific drug or poly-specific that can export multiple structurally diverse drug compounds. These proteins can be classified into seven groups based on protein sequence homology, energy source and overall structure. Extensive studies on efflux proteins have resulted in a wealth of knowledge that has made possible in-depth understanding of the structures and mechanisms of action, substrate profiles, regulation and possible inhibition of many clinically important efflux pumps. This review focuses on describing known families of drug efflux pumps using examples that are well characterized structurally and/or biochemically.
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http://dx.doi.org/10.1042/EBC20160064 | DOI Listing |
J Bacteriol
January 2025
Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), Department of Microbiology and Biotechnology, University of Tübingen, Tübingen, Baden-Württemberg, Germany.
Unlabelled: is well adapted to survive and persist in the infected host, escaping the host's immune response. Since polyamines such as spermine, which are synthesized by infected macrophages, are able to inhibit the growth of , the pathogen needs strategies to cope with these toxic metabolites. The actinomycete , a close relative of makes use of a gamma-glutamylation pathway to functionally neutralize spermine.
View Article and Find Full Text PDFAMB Express
January 2025
Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Candida albicans is a commensal fungus that naturally inhabits the vagina. However, overgrowth of C. albicans can result in vulvovaginal candidiasis (VVC), one of the most prevalent fungal infections affecting women.
View Article and Find Full Text PDFMicrobiol Spectr
January 2025
Department of Microbiology, University of Massachusetts, Amherst, Massachusetts, USA.
Unlabelled: is an acid-fast, aerobic, non-motile, and biofilm-forming bacterium. The increasing prevalence of mycobacterial infections makes it necessary to find new methods to combat the resistance of bacteria to conventional antibiotics. is an emerging pathogen that is intrinsically drug resistant due to several factors, including an impermeable cell envelope, drug efflux pumps, target-modifying enzymes, and the ability to form thick, robust biofilms.
View Article and Find Full Text PDFJ Antimicrob Chemother
January 2025
Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Background: The use of fluconazole for long-term oral candidiasis treatment in HIV/AIDS patients can potentially affect the clearance rate and antifungal efficacy of voriconazole against Talaromyces marneffei infection. We isolated two T. marneffei strains that were both resistant to fluconazole and voriconazole.
View Article and Find Full Text PDFPLoS Comput Biol
January 2025
Department of Physics, University of Toronto, Toronto, Ontario, Canada.
Efflux pumps that transport antibacterial drugs out of bacterial cells have broad specificity, commonly leading to broad spectrum resistance and limiting treatment strategies for infections. It remains unclear how efflux pumps can maintain this broad spectrum specificity to diverse drug molecules while limiting the efflux of other cytoplasmic content. We have investigated the origins of this broad specificity using theoretical models informed by the experimentally determined structural and kinetic properties of efflux pumps.
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