Biology:Multidrug resistance pump

From HandWiki
Schematic overview of the major families of bacterial multidrug efflux pumps. RND: Resistance-Nodulation cell Division superfamily; ABC: ATP Binding Cassette superfamily; MFS: Major Facilitator Superfamily; MATE: Multidrug and Toxic Compound Efflux family; DMT: Drug/Metabolite Transporter superfamily; PACE: Proteobacterial Antimicrobial Compound Efflux family; AbgT: p-Aminobenzoyl-glutamate Transporter family[1]

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.[2] 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.[3]

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.[3] 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.[3] 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.[4]

Because of their importance in drug evasion such as in antibiotic resistance, there is a growing about of research on Efflux pump inhibitors (EPIs).[5] Promising EPIs have been identified from plants,secondary metabolites[6] small molecule compounds,[7] or peptides derived from antibody fragments.[8][9]

References

  1. ↑ Pasqua, Martina; Bonaccorsi di Patti, Maria Carmela; Fanelli, Giulia; Utsumi, Ryutaro; Eguchi, Yoko; Trirocco, Rita; Prosseda, Gianni; Grossi, Milena et al. (2021-07-26). "Host - Bacterial Pathogen Communication: The Wily Role of the Multidrug Efflux Pumps of the MFS Family" (in en). Front. Mol. Biosci. 8. doi:10.3389/fmolb.2021.723274. PMID 34381818. 
  2. ↑ 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. 
  3. ↑ 3.0 3.1 3.2 Chitsaz, Mohsen; Brown, Melissa H. (2017-03-03). "The role played by drug efflux pumps in bacterial multidrug resistance" (in en). Essays in Biochemistry 61 (1): 127–139. doi:10.1042/EBC20160064. ISSN 0071-1365. PMID 28258236. 
  4. ↑ 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. PMID 25788514. 
  5. ↑ 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. 
  6. ↑ 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. PMID 32923005. 
  7. ↑ Cauilan, Allea; Ruiz, Cristian (2022-11-24). "Sodium Malonate Inhibits the AcrAB-TolC Multidrug Efflux Pump of Escherichia coli and Increases Antibiotic Efficacy". Pathogens 11 (12): 1409. doi:10.3390/pathogens11121409. ISSN 2076-0817. PMID 36558743. 
  8. ↑ Brawley, Douglas N.; Sauer, David B.; Li, Jianping; Zheng, Xuhui; Koide, Akiko; Jedhe, Ganesh S.; Suwatthee, Tiffany; Song, Jinmei et al. (July 2022). "Structural basis for inhibition of the drug efflux pump NorA from Staphylococcus aureus". Nature Chemical Biology 18 (7): 706–712. doi:10.1038/s41589-022-00994-9. 
  9. ↑ Haus‐Cohen, Maya; Assaraf, Yehuda G.; Binyamin, Liat; Benhar, Itai; Reiter, Yoram (May 2004). "Disruption of P‐glycoprotein anticancer drug efflux activity by a small recombinant single‐chain Fv antibody fragment targeted to an extracellular epitope". International Journal of Cancer 109 (5): 750–758. doi:10.1002/ijc.20037. 



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