Multidrug resistance pump

Multidrug resistance pumps (MDR pumps) also known Multidrug efflux pumps are a type of efflux pump and P-glycoprotein. MDR pumps in the cell membrane extrudes many foreign substances out of the cells and some pumps can have a broad specificity.[1] MDR pumps exist in animals, fungi, and bacteria and likely evolved as a defense mechanism against harmful substances. There are seven families of MDRs and are grouped by homology, energy source, and overall structure.[2]

There are five major classes of efflux pumps in bacteria: the ATP-binding cassette (ABC) superfamily, the resistance nodulation division (RND) superfamily, the major facilitator superfamily (MFS), the small multidrug resistance (SMR) superfamily, and the multidrug and toxic compound extrusion (MATE) family. There are also two minor classes: the proteobacterial antimicrobial compound efflux (PACE) family, and the p-aminobenzoyl-glutamate transporter (AbgT) family.[2] The ABC superfamily uses ATP as an energy source for export while the rest of the efflux pumps use proton motive force. Between them, the efflux pump classes cover a wide range of substrate specificities and are involved in numerous cellular processes including cell-to-cell communication, biofilm formation, virulence, and impart cellular protection through extrusion of toxic metabolic byproducts, toxic compounds, and clinical antibiotics.

Extrusion of compounds by efflux pumps is energy dependent.[2] ABC transporters use ATP hydrolysis for efflux. The rest of the characterized pumps use proton motive force. The increased use in antibiotics has resulted in a concomitant increase in antibiotic resistant bacteria. Pathogenic bacterial and fungal species have developed MDR pumps which efflux out many antibiotics and antifugals, increasing the concentration needed for their effect. In bacteria, overexpression of some efflux pumps can result in decreased susceptibility to multiple antibiotics.[3]

Because of their importance in drug evasion such as in antibiotic resistance, there is a growing about of research on Efflux pump inhibitors (EPIs).[4] Many promising EPIs come from plant secondary metabolites[5] and small molecule compounds.[6]

References
  1. Laura J. V. Piddock (2006). "Multidrug-resistance efflux pumps ? not just for resistance". Nature Reviews Microbiology. 4 (8): 629–636. doi:10.1038/nrmicro1464. PMID 16845433. S2CID 3336576.
  2. Chitsaz, Mohsen; Brown, Melissa H. (2017-03-03). "The role played by drug efflux pumps in bacterial multidrug resistance". Essays in Biochemistry. 61 (1): 127–139. doi:10.1042/EBC20160064. ISSN 0071-1365. PMID 28258236.
  3. Li, Xian-Zhi; Plésiat, Patrick; Nikaido, Hiroshi (April 2015). "The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria". Clinical Microbiology Reviews. 28 (2): 337–418. doi:10.1128/CMR.00117-14. ISSN 0893-8512. PMC 4402952. PMID 25788514.
  4. AlMatar, Manaf; Albarri, Osman; Makky, Essam A.; Köksal, Fatih (February 2021). "Efflux pump inhibitors: new updates". Pharmacological Reports. 73 (1): 1–16. doi:10.1007/s43440-020-00160-9. ISSN 2299-5684. PMID 32946075. S2CID 221786479.
  5. Seukep, Armel Jackson; Kuete, Victor; Nahar, Lutfun; Sarker, Satyajit D.; Guo, Mingquan (August 2020). "Plant-derived secondary metabolites as the main source of efflux pump inhibitors and methods for identification". Journal of Pharmaceutical Analysis. 10 (4): 277–290. doi:10.1016/j.jpha.2019.11.002. ISSN 2095-1779. PMC 7474127. PMID 32923005.
  6. Cauilan, Allea; Ruiz, Cristian (2022-11-24). "Sodium Malonate Inhibits the AcrAB-TolC Multidrug Efflux Pump of Escherichia coli and Increases Antibiotic Efficacy". Pathogens (Basel, Switzerland). 11 (12): 1409. doi:10.3390/pathogens11121409. ISSN 2076-0817. PMC 9781404. PMID 36558743.
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