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Multidrug Efflux Pumps in Bacteria and Efflux Pump Inhibitors

Abhirami P. Sreekantan
Abhirami P. Sreekantan
, 
Pooja P. Rajan
Pooja P. Rajan
, 
Minsa Mini
Minsa Mini
 y 
Praveen Kumar
Praveen Kumar
   | 24 jul 2022
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Publicado en línea: 24 jul 2022
Páginas: -
Recibido: 01 mar 2022
Aceptado: 01 may 2022
DOI: https://doi.org/10.2478/am-2022-0009
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© 2022 Abhirami P. Sreekantan et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1

Schematic representation of five superfamilies of EPs found in bacteria(ABC) ATP-Binding Cassette Superfamily [17]; (MFS) Major Facilitator Superfamily [18]; (MATE) Multidrug And Toxic Compound Extrusion Family [19]; (SMR) Small Multi-Drug Resistance Family [20]; (RND) Resistance-Nodulation-Division Superfamily [21].
Schematic representation of five superfamilies of EPs found in bacteria(ABC) ATP-Binding Cassette Superfamily [17]; (MFS) Major Facilitator Superfamily [18]; (MATE) Multidrug And Toxic Compound Extrusion Family [19]; (SMR) Small Multi-Drug Resistance Family [20]; (RND) Resistance-Nodulation-Division Superfamily [21].

List of Efflux Pump Inhibitors based on mechanism of action, origin, targets and substrates

Mechanism of action/Compounds EPIs Target EPs Bacteria Substrates References
1. Mechanism of Action
Energy Disruption CCCP-Carbonyl cyanide chlorophenyl hydrazone MFS- tetA, tetB H. pylori, Klebsiella spp. Tetracycline [98, 99]
Synthetic EPI- IITR08027 MATE- abeM E. coli, A. baumanii Fluoroquinolones [100]
PAβN RND- mexAB-oprM, mexCD-oprJ, mexEF-oprN P. aeruginosa LevofloxacinErythromycinStreptomycin [90, 101]
Competitive Inhibition Verapamil MATE- dinF and norM M. tuberculosis BedaquilineOfloxacin [102]
1-(1-napthylmethyl)-piperazine (NMP) RND- acrAB, acrEF E. coli LevofloxacinRifampinChloramphenicol [103]
2. Plant origin
Alkaloids Reserpine (Rawfolia serpentia) MFS- norA, tetK, Bmr MATE- mepA S. aureusBacillus subtilisStreptococcus pneumoniae NorfloxacinTetracyclineCiprofloxacin [104]
Piperine (Piper nigram) ABC transporters MFS- norA S. aureus, Mycobacterium tuberculosis CiprofloxacinRifampicin [105]
Conessine (Holarrheaa antidysenterica) RND- adeIJK, mexAB-oprM Acinetobacter baumannii Rifampicin Novobiocin [91]
Flavanoids Baicalein (Thymus vulgaris) MFS- tetK, norA Staphylococci TetracyclineCiprofloxacin [106, 107]
5′-methoxy-hydnocarpin (Berberis fremontii) MFS- norA S. aureus TetracyclineNorfloxacinBerberine [108]
Genistein (Isoflavone) MFS- norA S. aureus Berberine [109]
Epigallocatechin gallate MFS- tetK StaphylococciCamphylobacter TetracyclineErythromycinCiprofloxacin [110]
Polyphenols Curcumin (Curcuma longa) MFS- norA RND S. aureusP. aeruginosa NorfloxacinCiprofloxacinGentamicin [111, 112]
Coumarin (Mesua ferrea) MFS- norA S. aureus NorfloxacinCiprofloxacin [113]
Phenolic diterpenes Carnosic acid (Rosmarinus officinalis) ABC transporter msrA S. aureus Erythromycin [114]
Monoterpenoid Carnosol (Rosmarinus officinalis) ABC transporter msrA MFS- tetK S. aureus Tetracycline [114]
Geraniol (Helichrysum italicum) RND- acrAB-tolC Enterobacter aerogenes Chloramphenicol [115]
Catharanthine (Catharanthus roseus) RND- mexAB-oprM P. aeruginosa TetracyclineStreptomycin [116]
3. Synthetic origin
Quinolone derivatives Pyridoquinolones RND- acrAB-tolC Enterobacter aerogenes Norfloxacin [117]
Arylpiperidines and aryl piperazine derivatives Phenylpiperadines RND- acrAB-tolC E. coli Linezolid [118]
Pyridopyrimidine and pyranopyridine derivatives D2 and D13-9001MBX2319 RND- mexAB-oprMRND- acrAB-tolC P. aeruginosaE. coli FluoroquinolonesFluoroquinolones [119, 120][121]
Naphthyridine derivatives 1,8-naphthyridines sulfonamide MFS- norA S. aureus NorfloxacinEthidium bromide [97]
Boronic acid derivatives 6-(3-Phenylpropoxy) pyridine-3-boronic acid MFS- norA S. aureus CiprofloxacinEthidium bromide [122]
Indole derivatives 3-amino-6-carboxyl-indole3-nitro-6-amino-indole RND- acrAB-tolC E. coli ChloramphenicolTetracyclineErythromycinCiprofloxacin [123, 124]
4. Clinically approved drug
Hypoglycemic biguanide drug Metformin RND- acrAB-tolC MATE- mdtK K. pneumoniae Ampicillin-sulbactamMeropenemAmikacin [125]
Tyrosine kinase Inhibitor Nilotinib MFS- EmrD S. aureus Ciprofloxacin [86]
Ergot alkaloid-vasoconstrictor Dihydroergotamine MFS- norA S. aureus Ciprofloxacin [86]
5. Microbial origin
EA-371α and EA-371d (fermentation extract of Streptomyces spp. RND- mexAB-oprM P. aeruginosa Levofloxacin [126]
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