From Polyphenols to β-Lactamases: Multitarget Strategies to Defeat Severe Resistance

Area of Science:

• Microbiology
• Pharmacology
• Public Health

Background:

• Antimicrobial resistance (AMR) is a critical global health threat, reducing antibiotic efficacy and increasing mortality.
• A lack of novel antibiotics necessitates alternative strategies to combat resistant bacteria.
• Natural compounds and synthetic inhibitors offer promising avenues to restore antibiotic effectiveness.

Purpose of the Study:

• To review recent literature on natural compounds and synthetic/semi-synthetic small-molecule inhibitors targeting AMR mechanisms.
• To highlight agents that restore antibiotic susceptibility or reduce bacterial virulence.
• To assess the potential of these agents as adjuvants in antimicrobial stewardship.

Main Methods:

• Narrative review of recent scientific literature.
• Analysis of studies documenting the activity of natural compounds and small-molecule inhibitors against AMR.
• Focus on agents targeting specific resistance mechanisms like efflux pumps, biofilms, and quorum sensing.

Main Results:

• Natural compounds (polyphenols, alkaloids, etc.) exhibit multitarget activities against bacteria.
• Synthetic inhibitors are designed to target specific resistance determinants (e.g., beta-lactamases, SOS response).
• These agents act as adjuvants, enhancing existing antibiotic efficacy without strong selective pressure.

Conclusions:

• Integrating natural compounds and targeted small-molecule inhibitors is a promising strategy to combat AMR.
• Further research and clinical trials are needed to implement these approaches in public health.
• These alternative strategies are crucial for mitigating the global burden of antimicrobial resistance.