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Multidrug Efflux Pumps in Bacteria and Efflux Pump Inhibitors Cover

Multidrug Efflux Pumps in Bacteria and Efflux Pump Inhibitors

Advancements of Microbiology
Volume 61 (2022): Issue 3 (September 2022)
By: Abhirami P. Sreekantan,  Pooja P. Rajan,  Minsa Mini and  Praveen Kumar  
Open Access
|Oct 2022

Figures & Tables

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/CompoundsEPIsTarget EPsBacteriaSubstratesReferences
1. Mechanism of Action
Energy DisruptionCCCP-Carbonyl cyanide chlorophenyl hydrazoneMFS- tetA, tetBH. pylori, Klebsiella spp.Tetracycline[98, 99]
Synthetic EPI- IITR08027MATE- abeME. coli, A. baumaniiFluoroquinolones[100]
PAβNRND- mexAB-oprM, mexCD-oprJ, mexEF-oprNP. aeruginosaLevofloxacinErythromycinStreptomycin[90, 101]
Competitive InhibitionVerapamilMATE- dinF and norMM. tuberculosisBedaquilineOfloxacin[102]
1-(1-napthylmethyl)-piperazine (NMP)RND- acrAB, acrEFE. coliLevofloxacinRifampinChloramphenicol[103]
2. Plant origin
AlkaloidsReserpine (Rawfolia serpentia)MFS- norA, tetK, BmrMATE- mepAS. aureusBacillus subtilisStreptococcus pneumoniaeNorfloxacinTetracyclineCiprofloxacin[104]
Piperine (Piper nigram)ABC transportersMFS- norAS. aureus, Mycobacterium tuberculosisCiprofloxacinRifampicin[105]
Conessine (Holarrheaa antidysenterica)RND- adeIJK, mexAB-oprMAcinetobacter baumanniiNovobiocinRifampicin[91]
FlavanoidsBaicalein (Thymus vulgaris)MFS- tetK, norAStaphylococciTetracyclineCiprofloxacin[106, 107]
5’-methoxy-hydnocarpin (Berberis fremontii)MFS- norAS. aureusTetracyclineNorfloxacinBerberine[108]
Genistein (Isoflavone)MFS- norAS. aureusBerberine[109]
Epigallocatechin gallateMFS- tetKStaphylococciCamphylobacterTetracyclineErythromycinCiprofloxacin[110]
PolyphenolsCurcumin (Curcuma longa)MFS- norARNDS. aureusP. aeruginosaNorfloxacinCiprofloxacinGentamicin[111, 112]
Coumarin (Mesua ferrea)MFS- norAS. aureusNorfloxacinCiprofloxacin[113]
Phenolic diterpenesCarnosic acid (Rosmarinus officinalis)ABC transporter msrAS. aureusErythromycin[114]
MonoterpenoidCarnosol (Rosmarinus officinalis)ABC transporter msrAMFS- tetKS. aureusTetracycline[114]
Geraniol (Helichrysum italicum)RND- acrAB-tolCEnterobacter aerogenesChloramphenicol[115]
Catharanthine (Catharanthus roseus)RND- mexAB-oprMP. aeruginosaTetracyclineStreptomycin[116]
3. Synthetic origin
Quinolone derivativesPyridoquinolonesRND- acrAB-tolCEnterobacter aerogenesNorfloxacin[117]
Arylpiperidines and aryl piperazine derivativesPhenylpiperadinesRND- acrAB-tolCE. coliLinezolid[118]
Pyridopyrimidine and pyranopyridine derivativesD2 and D13-9001RND- mexAB-oprMP. aeruginosaFluoroquinolones[119, 120]
MBX2319RND- acrAB-tolCE. coliFluoroquinolones[121]
Naphthyridine derivatives1,8-naphthyridines sulfonamideMFS- norAS. aureusNorfloxacinEthidium bromide[97]
Boronic acid derivatives6-(3-Phenylpropoxy) pyridine-3-boronic acidMFS- norAS. aureusCiprofloxacinEthidium bromide[122]
Indole derivatives3-amino-6-carboxyl-indole3-nitro-6-amino-indoleRND- acrAB-tolCE. coliChloramphenicolTetracyclineErythromycinCiprofloxacin[123, 124]
4. Clinically approved drug
Hypoglycemic biguanide drugMetforminRND- acrAB-tolCMATE- mdtKK. pneumoniaeAmpicillin-sulbactamMeropenemAmikacin[125]
Tyrosine kinase InhibitorNilotinibMFS- EmrDS. aureusCiprofloxacin[86]
Ergot alkaloid-vasoconstrictorDihydroergotamineMFS- norAS. aureusCiprofloxacin[86]
5. Microbial origin
EA-371α and EA-371d (fermentation extract of Streptomyces spp.RND- mexAB-oprMP. aeruginosaLevofloxacin[126]
DOI: https://doi.org/10.2478/am-2022-009 | Journal eISSN: 2545-3149 | Journal ISSN: 0079-4252
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Language: English, Polish
Page range: 105 - 114
Submitted on: Mar 1, 2022
Accepted on: May 1, 2022
Published on: Oct 4, 2022
Published by: Polish Society of Microbiologists
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
Antimicrobial resistance,
MDR,
Multidrug efflux pumps,
Biofilm,
Efflux Pump Inhibtor (EPI)
Related subjects:
Life sciences,
Microbiology and virology

© 2022 Abhirami P. Sreekantan, Pooja P. Rajan, Minsa Mini, Praveen Kumar, published by Polish Society of Microbiologists
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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