Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics
Abstract
:1. Introduction
- (1)
- targeting antimicrobial-resistant enzymes;
- (2)
- targeting antimicrobial-resistant bacteria;
- (3)
- drug delivery systems;
- (4)
- physiochemical methods; and
- (5)
- unconventional strategies.
2. Historical Perspectives
3. Conventional Antibiotics to Combination Therapy
3.1. Antibiotics Groups and Their Mode of Action
3.2. Understanding AMR Mechanisms and the Use of Inhibitors
- (1)
- Enzymatic degradation of antibiotics, e.g., bacterial synthesis of β-lactamases that degrade the β-lactam class of antibiotics;
- (2)
- Modification of the antibiotic target, i.e., the target becomes modified so that the antibiotic is no longer able to bind to its site of action;
- (3)
- Control of drug entry through mutations in bacterial cell wall porin molecules and membrane modifications;
- (4)
- Activation of efflux pump systems that are able to pump antibiotics out of the cell before antibiotic–target interactions take place.
- (a)
- AMR gene silencers, which silence the AMR genes, e.g.: CRISPR-Cas system
- (b)
- Ribosomal inhibitors, which bind with ribosomal subunits and alter the protein production so that the bacteria cannot fight by proteins; and
- (c)
- efflux pump inhibitors.
3.3. Combination Therapy
3.3.1. Antibiotic Combinations
3.3.2. Antibiotic Combination with β-Lactamase INHIBITORS
3.3.3. Combination of Antibiotics with Biocides
4. Strategies Targeting Antimicrobial-Resistant Enzymes
4.1. Enzyme Inhibitors
4.2. Medicinal Plants and Phytochemicals
4.3. Small Molecules-Improved Chemical Entities (ICE)
4.4. Essential Oils
4.5. RNA Silencing
4.6. CRISPR-Cas System
5. Strategies Targeting Antimicrobial-Resistant Bacteria
5.1. Lantibiotics and Bacteriocins
5.2. Antimicrobial Peptides (AMP)–Including AMP + Antibiotics Combination
5.3. Insect Derived Enzymes and AMPs
5.4. Nanoparticle Based Strategies
5.5. Coinfection Strategies & Probiotic Bacteria against Pathogens
5.6. Utility of Monoclonal Antibodies against Pathogens
5.7. Bacteriophages Based-Specific or Selective or Both!
5.7.1. Phage Therapy
5.7.2. Phage-Derived Lytic Proteins as a Antibacterials
5.8. Biofilm Dispersion Methods
5.9. Discovery and Role of Anti-Persister Antimicrobials
5.10. Disruption of Quorum Sensing
6. Strategies Based on Drug Delivery Systems
6.1. Facilitated Drug Delivery Systems
6.2. Anti-Plasmid and Plasmid Curing-However, Not Suitable for In Vivo
6.3. Antivirulence Compounds
7. Physicochemical Methods
7.1. Atmospheric Pressure Non-Thermal Plasma (APNTP)
7.2. Sonodynamic Antimicrobial Chemotherapy
7.3. Photoinactivation
7.4. Other Physicochemical Means
8. Expected Role of Vaccines in Combating AMR Pathogens
9. Unconventional Strategies
10. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Antibiotic Class | Mechanism of Action | References |
---|---|---|
Beta lactams: carbapenems, cephalosporins, monobactam, penicillin, glycopeptides | Inhibit cell wall synthesis | [15] |
Lipopeptides | Depolarize cell membrane | [16] |
Aminoglycosides, tetracyclines Chloramphenicol, macrolides | Inhibit protein synthesis by binding to 30S ribosomal unit and 50S ribosomal unit | [17,18] |
Quinolones | Inhibit nucleic acid synthesis | [19] |
Sulfonamides, trimethoprim | Inhibit metabolic pathways | [20] |
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Murugaiyan, J.; Kumar, P.A.; Rao, G.S.; Iskandar, K.; Hawser, S.; Hays, J.P.; Mohsen, Y.; Adukkadukkam, S.; Awuah, W.A.; Jose, R.A.M.; et al. Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics. Antibiotics 2022, 11, 200. https://doi.org/10.3390/antibiotics11020200
Murugaiyan J, Kumar PA, Rao GS, Iskandar K, Hawser S, Hays JP, Mohsen Y, Adukkadukkam S, Awuah WA, Jose RAM, et al. Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics. Antibiotics. 2022; 11(2):200. https://doi.org/10.3390/antibiotics11020200
Chicago/Turabian StyleMurugaiyan, Jayaseelan, P. Anand Kumar, G. Srinivasa Rao, Katia Iskandar, Stephen Hawser, John P. Hays, Yara Mohsen, Saranya Adukkadukkam, Wireko Andrew Awuah, Ruiz Alvarez Maria Jose, and et al. 2022. "Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics" Antibiotics 11, no. 2: 200. https://doi.org/10.3390/antibiotics11020200