[Active efflux as the multidrug resistance mechanism]
Anna Wasaznik1, Mariusz Grinholc, Krzysztof P Bielawski
1Pracownia Diagnostyki Molekularnej, Katedra Biotechnologii, Miedzyuczelniany Wydział Biotechnologii Uniwersytetu Gdańskiego i Akademii Medycznej w Gdańsku, 80-822 Gdańsk.
Abstract:
Active efflux is a common resistance mechanism in a wide range of bacterial pathogens. It is responsible for the transport of such toxic compounds as drugs, toxins, and detergents. Pumps with broad substrate profiles promote the emergence of multidrug-resistant bacterial pathogens that are a particular threat to contemporary medicine, such as Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Salmonella enterica sv Typhimurium. One can distinguish five major class of transport systems on the basis of their structure and function: MFS (major facilitator superfamily), SMR (small multidrug-resistance family), MATE (multidrug and toxic compound extrusion family), ABC (ATP binding cassette superfamily), and RND (resistance nodulation cell division family). Substrate transport may include hydrogen proton exchange or energy generated via ATP hydrolysis. The transport is effectively regulated by local regulatory proteins.such as BmrR from Bacillus subtilis, or by the global bacterial regulatory system. Investigations into efflux pumps and their substrate profiles and regulatory mechanisms have led to the discovery of new therapeutics and pump inhibitors that could potentially become alternative and effective antimicrobial drugs. Additionally, some alternative therapies such as photodynamic inactivation could be more effective if the synergistic action of efflux pump inhibitors are used.Thus research into efflux transport systems seems to be an important element of contemporary medicine .
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