Defeating Antibiotic-Resistant Bacteria: Exploring Alternative Therapies for a Post-Antibiotic Era
Abstract
:1. Introduction
2. Combination Therapy I: Increases Membrane Permeability
3. Combination Therapy II: Reduces Efflux Pump Activity
4. Combination Therapy III: Inhibits Kinase Activity and Intrinsic Antibiotic Resistance
5. Anti-Regulators
6. Anti-Quorum Sensing System
7. Anti-Bacterial Virulence Factors (Adhesion and Motility)
8. Anti-Toxins and Secretion System
9. Engineered Bacteriophage
10. Modulate the Microbiome
11. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Compound | Structure and Molecular Weight | Action | Function | Reference |
---|---|---|---|---|
Mitotane | 320 g/mol | Unknown | Combine with polymyxin B to target carbapenem-resistant P. aeruginosa, A. baumannii, and K. pneumoniae | [24] |
SPR741 | 992.1 g/mol | Disrupts the bacterial outer membrane, permeabilizing it to antibiotics | Combine with antibiotics to target antibiotic-resistant E. coli, K. pneumoniae, and A. baumannii | [25,26] |
Phenylalanyl arginyl β-naphthylamide (PAβN) | 446.5 g/mol | Inhibits Gram-negative efflux pumps | Combine with antibiotics to target fluoroquinolones- resistant P. aeruginosa | [31,32] |
Curcumin | 368.4 g/mol | Efflux pump inhibitor | Combine with antibiotics target multidrug- resistant P. aeruginosa | [33] |
Quinazoline compounds-GI261520A | 357.4 g/mol | Inhibits kinase activity of PhoP/PhoQ two-component system | Anti-virulence effect by blocking S. Typhimurium intramacrophage replication | [34] |
GW779439X | 454.5 g/mol | Inhibits S. aureus PASTA kinase Stk1 activity | Resensitizes methicillin-resistant S. aureus to various β-lactams | [35] |
Virstatin | 283.28 g/mol | Inhibits dimerization of regulator ToxT of V. cholerae | Reduces the nization of V. cholera in a murine model of infection | [36,37] |
LED209 | 383.5 g/mol | Anti-E. coli quorum sensing system | Abolishes EHEC A/E lesion formation and decreases expression of shiga toxin | [38] |
Quercitrin | 448.4 g/mol | Inhibits the enzymatic activity of surface protein sortase A (SrtA) | Reduces attachment of S. aureus to fibronectin-coated or fibrinogen-coated surface; inhibits biofilm formation of S. pneumoniae | [39,40] |
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Wang, C.-H.; Hsieh, Y.-H.; Powers, Z.M.; Kao, C.-Y. Defeating Antibiotic-Resistant Bacteria: Exploring Alternative Therapies for a Post-Antibiotic Era. Int. J. Mol. Sci. 2020, 21, 1061. https://doi.org/10.3390/ijms21031061
Wang C-H, Hsieh Y-H, Powers ZM, Kao C-Y. Defeating Antibiotic-Resistant Bacteria: Exploring Alternative Therapies for a Post-Antibiotic Era. International Journal of Molecular Sciences. 2020; 21(3):1061. https://doi.org/10.3390/ijms21031061
Chicago/Turabian StyleWang, Chih-Hung, Yi-Hsien Hsieh, Zachary M. Powers, and Cheng-Yen Kao. 2020. "Defeating Antibiotic-Resistant Bacteria: Exploring Alternative Therapies for a Post-Antibiotic Era" International Journal of Molecular Sciences 21, no. 3: 1061. https://doi.org/10.3390/ijms21031061