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The ABC family of multidrug transporters in microorganisms
1Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan, The Netherlands. h.w.van.veen@biol.rug.nl
Abstract:
Multidrug transporters are membrane proteins that are able to expel a broad range of toxic molecules from the cell. In humans, the overexpression of the multidrug resistance P-glycoprotein (Pgp) and the multidrug resistance-associated protein MRP1 (MRP) is a principal cause of resistance of cancers to chemotherapy. These multidrug transporters belong to the ATP-binding cassette (ABC) family of transport proteins that utilize the energy of ATP hydrolysis for activity. In microorganisms, multidrug transporters play an important role in conferring antibiotic resistance on pathogens. In the last decade, homologs of human Pgp and MRP have been found in microorganisms such as Plasmodium falciparum, Candida albicans, Saccharomyces cerevisiae and, more recently, in Lactococcus lactis. In this review, we will summarize the current state of knowledge on three major aspects of microbial ABC-type multidrug transporters: (i) the functional and structural similarities among these proteins in prokaryotic and eukaryotic cells, (ii) the molecular mechanism of these transporters, and (iii) their potential physiological role.
Insights
Microbial multidrug transporters, similar to human P-glycoprotein (Pgp) and MRP1, are ATP-binding cassette (ABC) proteins. This review explores their similarities, mechanisms, and roles in antibiotic resistance.
Area of Science:
- Biochemistry
- Molecular Biology
- Microbiology
Background:
- Multidrug transporters, including P-glycoprotein (Pgp) and MRP1, are ABC proteins that confer drug resistance in humans.
- These transporters expel a wide array of toxic compounds from cells.
- In microorganisms, similar transporters are crucial for antibiotic resistance in pathogens.
Purpose of the Study:
- To review microbial ATP-binding cassette (ABC)-type multidrug transporters.
- To summarize functional and structural similarities between microbial and human transporters.
- To elucidate the molecular mechanisms and physiological roles of these microbial transporters.
Main Methods:
- Literature review of microbial ABC-type multidrug transporters.
- Comparative analysis of functional and structural data.
- Examination of molecular mechanisms and physiological roles.
Main Results:
- Homologs of human Pgp and MRP have been identified in various microorganisms.
- These microbial transporters share functional and structural similarities with their human counterparts.
- Evidence suggests significant roles in conferring antibiotic resistance.
Conclusions:
- Microbial ABC-type multidrug transporters are functionally and structurally analogous to human Pgp and MRP.
- Understanding their molecular mechanisms is key to combating microbial drug resistance.
- These transporters play vital physiological roles in microorganisms.
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