[Efflux-mediated antimicrobial multidrug resistance]
Agata Jarmuła1, Ewa Obłąk, Donata Wawrzycka
1Instytut Genetyki i Mikrobiologii, Uniwersytet Wrocławski.
Abstract:
Multidrug resistance is a major problem in the treatment of infectious diseases caused by bacteria and fungi. One of the basic mechanisms of resistance is active efflux of distinct drugs from cells. Export of toxic compounds from bacterial cells is mediated by proteins of 5 distinct families: MF, SMR, ABC, RND and MATE. The substrate spectrum of efflux pumps includes antibiotics, chemotherapeutics and detergents. Genes that determine resistance can be located on chromosomes or mobile elements (plasmids, transposons, integrons). The presence of resistance genes on mobile elements enables bacteria to transfer those genes between cells and spread the multidrug resistance phenotype. There are several inhibitors of efflux pumps that are currently in the experimental phase. Proteins that mediate multidrug resistance are also present in fungal cells. They belong mainly to the ABC superfamily of transporters and PDR subfamily. These efflux pumps are widely investigated in Saccharomyces cerevisiae.
Insights
Multidrug resistance in infections stems from active drug efflux by bacterial and fungal proteins. Inhibitors are being developed to combat this challenge, which spreads via mobile genetic elements.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Context:
- Multidrug resistance (MDR) poses a significant challenge in treating bacterial and fungal infections.
- Active efflux of drugs by cellular pumps is a primary resistance mechanism.
- Efflux pumps export a wide range of compounds, including antibiotics and antifungals.
Purpose:
- To elucidate the mechanisms of multidrug resistance mediated by efflux pumps in bacteria and fungi.
- To highlight the role of efflux pump proteins in drug export and resistance.
- To discuss the genetic basis of resistance and potential therapeutic strategies.
Summary:
- Bacterial multidrug resistance involves efflux pumps from five families (MF, SMR, ABC, RND, MATE) exporting diverse substrates.
- Resistance genes on mobile elements facilitate rapid spread of multidrug resistance.
- Fungal multidrug resistance also involves efflux pumps, notably the ABC superfamily's PDR subfamily, extensively studied in Saccharomyces cerevisiae.
Impact:
- Understanding efflux pump function is crucial for developing novel antimicrobial therapies.
- Targeting efflux pumps offers a strategy to overcome existing drug resistance.
- Research into efflux pump inhibitors (EPIs) is vital for combating infectious diseases.
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