Do Multiple Drug Resistance Transporters Interfere with Cell Functioning under Normal Conditions?
Autor: | Atanu Banerjee, Dmitry A. Knorre, Rajendra Prasad, Kseniia V. Galkina, T. Shirokovskikh |
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Rok vydání: | 2020 |
Předmět: |
0303 health sciences
Chemistry Cell Membrane 030302 biochemistry & molecular biology Cell Membrane Transport Proteins Transporter General Medicine Biochemistry Drug Resistance Multiple Yeast Cell biology Fungal Proteins Multiple drug resistance 03 medical and health sciences Adenosine Triphosphate Membrane medicine.anatomical_structure ATP hydrolysis Yeasts medicine Efflux Lipid bilayer |
Zdroj: | Biochemistry (Moscow). 85:1560-1569 |
ISSN: | 1608-3040 0006-2979 |
Popis: | Eukaryotic cells rely on multiple mechanisms to protect themselves from exogenous toxic compounds. For instance, cells can limit penetration of toxic molecules through the plasma membrane or sequester them within the specialized compartments. Plasma membrane transporters with broad substrate specificity confer multiple drug resistance (MDR) to cells. These transporters efflux toxic compounds at the cost of ATP hydrolysis (ABC-transporters) or proton influx (MFS-transporters). In our review, we discuss the possible costs of having an active drug-efflux system using yeast cells as an example. The pleiotropic drug resistance (PDR) subfamily ABC-transporters are known to constitutively hydrolyze ATP even without any substrate stimulation or transport across the membrane. Besides, some MDR-transporters have flippase activity allowing transport of lipids from inner to outer lipid layer of the plasma membrane. Thus, excessive activity of MDR-transporters can adversely affect plasma membrane properties. Moreover, broad substrate specificity of ABC-transporters also suggests the possibility of unintentional efflux of some natural metabolic intermediates from the cells. Furthermore, in some microorganisms, transport of quorum-sensing factors is mediated by MDR transporters; thus, overexpression of the transporters can also disturb cell-to-cell communications. As a result, under normal conditions, cells keep MDR-transporter genes repressed and activate them only upon exposure to stresses. We speculate that exploiting limitations of the drug-efflux system is a promising strategy to counteract MDR in pathogenic fungi. |
Databáze: | OpenAIRE |
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