Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition
Abstract
:1. Introduction
2. Staphylococcal Infections as a Global Health Problem Requiring Urgent Attention
3. Development and Dissemination of Multidrug Resistance in Staphylococci
4. Molecular Mechanisms of Antimicrobial Resistance in Staphylococci
5. Efflux-Mediated Antimicrobial Resistance: Clinical Implications
6. Major Classes of Bacterial Efflux Pumps
7. Prototypical Characterised Efflux Pumps in Staphylococci
7.1. NorA, NorB and NorC Efflux Proteins
7.2. TetA(K) and Tet38 Efflux Pumps
7.3. QacA Multidrug Efflux Protein
8. Commonly Used Methodological Approaches for Evaluating Efflux Inhibition in Staphylococci
9. In Quest of Staphylococcal Efflux Pump Inhibitors
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Family | Transporter | TMS | Gene Location | Prominent Substrates | Reference(s) |
---|---|---|---|---|---|
ABC | AbcA | 12 | Chromosome | Hydrophobic β-lactams | [104] |
MsrA | 12 | Plasmid | Macrolides, type B streptogramins, erythromycin | [105,106] | |
Sav1866 | 12 | Chromosome | Vinblastine, doxorubicin, Dyes (ethidium, Hoechst 33,342) | [107,108] | |
VgaA | 12 | Plasmid | Lincosamides, streptogramin A, pleuromutilins | [109,110] | |
VgaB | 12 | Plasmid | Pristinamycin, streptogramin A, streptogramin B virginiamycin, mikamycin, synergistin, dalfopristin | [111,112] | |
MATE | MepA | 12 | Chromosome | Fluoroquinolones (norfloxacin, ciprofloxacin, moxifloxacin), Glycylcyclines (tigecycline), QACs (benzalkonium, cetrimide), Dyes (ethidium) | [113,114,115] |
MFS | FexA | 14 | Transposon | All phenicols | [103,116] |
LmrS | 14 | Chromosome | Lincomycin, Oxazolidinone (linezolid), Phenicols (chloramphenicol), QACs (tetraphenylphosphonium), Dyes (ethidium) | [117,118] | |
MdeA | 14 | Chromosome | Fluoroquinolones (norfloxacin, ciprofloxacin), QACs (benzalkonium, dequalinium), Dyes (ethidium) | [90,119,120] | |
NorA | 12 | Chromosome | Fluoroquinolones (norfloxacin, ciprofloxacin), QACs (benzalkonium), Dyes (ethidium, rhodamine) | [121,122] | |
NorB | 14 | Chromosome | Fluoroquinolones (norfloxacin, ciprofloxacin, moxifloxacin), QACs (cetrimide), Dyes (ethidium) | [123,124] | |
NorC | 14 | Chromosome | Fluoroquinolones (ciprofloxacin, moxifloxacin), Dyes (rhodamine) | [125,126] | |
QacA | 14 | Plasmid | QACs (benzalkonium, dequalinium), Diamidines (pentamidine), Biguanidines (chlorhexidine), Dyes (ethidum, rhodamine, acriflavine) | [127,128,129,130] | |
QacB | 14 | Plasmid | QACs (benzalkonium), Dyes (ethidium, rhodamine 6G, acriflavine) | [127,131] | |
SdrM | 14 | Chromosome | Fluoroquinolones (norfloxacin), Dyes (ethidium, acriflavine) | [27,103,132] | |
TetA(K) | 14 | Plasmid | Tetracyclines | [122,133] | |
Tet38 | 14 | Chromosome | Tetracyclines, certain unsaturated fatty acids fosfomycin | [134] | |
RND | FarE | 12 | Chromosome | linoleic and arachidonic acids, rhodomyrtone | [102,135] |
SMR | QacC | 4 | Plasmid | QACs (benzalkonium, cetrimide), Dyes (ethidium) | [136,137,138] |
QacJ | 4 | Plasmid | QACs (benzalkonium, cetyltrimethylammonium bromide) | [139] | |
QacG | 4 | Plasmid | Benzalkonium, ethidium | [140,141] | |
QacH | 4 | Plasmid | Benzalkonium, ethidium, proflavine | [141,142] | |
SepA | 4 | Chromosome | Benzalkonium, chlorhexidine, acriflavine | [143,144] |
EPI Compound 1 | Chemical Class | Structure | Efflux Pump(s) | Antimicrobials 2,3 | Reference |
---|---|---|---|---|---|
15-copaenol | terpene | | NorA | EtBr, ciprofloxacin | [184] |
α-bisabolol | terpene | | NorA, TetK | Norfloxacin, tetracycline | [269] |
α-terpinene | terpene | | TetK | EtBr, tetracycline | [270] |
benzophenanthridine | alkaloid | | NorA | EtBr, ciprofloxacin | [271] |
boeravinone B | flavonoid | | NorA | EtBr, ciprofloxacin | [190] |
chalcone | flavonoid | | MepA, NorA | EtBr, norfloxacin | [272] |
baicalein | flavonoid | | MsrA, NorA | erythromycin, ciprofloxacin | [273] |
caffeic acid | polyphenol | | MsrA, NorA | EtBr, erythromycin, norfloxacin | [274] |
caffeoylquinic acids | polyphenol | | NorA | EtBr, ciprofloxacin, norfloxacin | [275] |
capsaicin | alkaloid | | NorA | EtBr, ciprofloxacin | [276] |
coumarin | polyphenol | | NorA | EtBr, norfloxacin | [277] |
curcumin | polyphenol | | NorA | ciprofloxacin | [278] |
dimethyl octanol | terpene | | NorA | EtBr, norfloxacin | [279] |
genistein | flavonoid | | NorA | EtBr, ciprofloxacin | [280] |
indirubin | alkaloid | | NorA | ciprofloxacin | [281] |
kaempferol rhamnoside | flavonoid | | NorA | EtBr, ciprofloxacin | [282] |
limonene | terpene | | MepA | EtBr, ciprofloxacin | [283] |
nerol | terpene | | NorA | EtBr, norfloxacin | [279] |
olympicin A | flavonoid | | NorA | enoxacin | [284] |
osthol | polyphenol | | NorA | ciprofloxacin | [278] |
phyllanthin | polyphenol | | NorA | EtBr, norfloxacin | [285] |
piperine | alkaloid | | MdeA, NorA | EtBr, mupirocin, ciprofloxacin | [286,287] |
tannic acid | polyphenol | | NorA | EtBr, norfloxacin | [288] |
EPI Compound | Structure 1 | Efflux Pump(s) | Antimicrobials 2 | Reference |
---|---|---|---|---|
3-(1-chloro-3,4-dihydronaphthalen-2-yl) acrylic acid | | NorA | EtBr, ciprofloxacin | [289] |
aglycone and 3-O-glycoside forms of flavonoids | | NorA | EtBr, ciprofloxacin | [290] |
aminophenyl chalcone | | MepA | EtBr, ciprofloxacin | [291] |
3-aryl-4-methyl-2-quinolones | | NorA | EtBr, ciprofloxacin | [292] |
benzothiazine 5,5-dioxide derivatives | | NorA | EtBr, ciprofloxacin | [293] |
bis-indolic derivatives | | NorA | ciprofloxacin | [294] |
boronic acid derivatives | | NorA | ciprofloxacin | [266] |
chalcone derivatives | | NorA | EtBr, ciprofloxacin | [295] |
cinnamamide derivatives | | NorA | ciprofloxacin | [296] |
dithiazole thione derivative | | NorA | EtBr, ciprofloxacin | [297] |
1-(1H-indol-3-yl)ethanamine derivatives | | NorA | EtBr, ciprofloxacin | [298] |
4-ethylpiperic acid amide derivatives | | NorA | EtBr, ciprofloxacin | [299] |
eugenol derivatives | | NorA | EtBr, norfloxacin | [300] |
hydroxyamines derived from lapachol and norlachol | | MrsA, TetK | EtBr, erythromycin, tetracycline | [301] |
indole-based compounds | | NorA | EtBr, ciprofloxacin | [181] |
murucoidins | | NorA | norfloxacin | [302] |
1,8-naphthyridine sulfonamides | | NorA | EtBr, norfloxacin | [303] |
1,3,4-oxadiazole conjugates of capsaicin | | NorA | EtBr, ciprofloxacin | [304] |
2-phenyl-4-hydroxyquinoline derivatives | | NorA | EtBr, norfloxacin | [305] |
2-phenylquinoline core | | NorA | EtBr, ciprofloxacin | [243] |
piperic acid amide derivatives | | NorA | EtBr, ciprofloxacin | [299] |
3-(substituted 3,4-dihydronaphthyl)-propenoic acid amides | | NorA | EtBr, ciprofloxacin | [306] |
riparin-derived compounds | | NorA | EtBr, ciprofloxacin, norfloxacin | [188] |
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Dashtbani-Roozbehani, A.; Brown, M.H. Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition. Antibiotics 2021, 10, 1502. https://doi.org/10.3390/antibiotics10121502
Dashtbani-Roozbehani A, Brown MH. Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition. Antibiotics. 2021; 10(12):1502. https://doi.org/10.3390/antibiotics10121502
Chicago/Turabian StyleDashtbani-Roozbehani, Abolfazl, and Melissa H. Brown. 2021. "Efflux Pump Mediated Antimicrobial Resistance by Staphylococci in Health-Related Environments: Challenges and the Quest for Inhibition" Antibiotics 10, no. 12: 1502. https://doi.org/10.3390/antibiotics10121502