Decoding Bacterial Persistence: Mechanisms and Strategies for Effective Eradication

Area of Science:

• Microbiology
• Infectious Diseases
• Drug Discovery

Background:

• Antimicrobial resistance (AMR) is a major global health threat, often linked to treatment failures.
• Bacterial persisters, a distinct subpopulation of non-heritably drug-tolerant cells, are increasingly recognized for their role in infection recalcitrance and AMR.
• While AMR determinants have been extensively studied, bacterial persistence has been relatively overlooked.

Purpose of the Study:

• To review the contributing factors to the bacterial persister phenotype.
• To highlight the significance of bacterial persisters in recurring infections and AMR.
• To inform the development of novel therapeutic strategies targeting bacterial persisters.

Main Methods:

• Literature review of fundamental research on bacterial persisters over the past decade.
• Analysis of studies identifying unique tolerance factors in clinically relevant pathogens.
• Synthesis of current knowledge on persister cell biology and their role in treatment failure.

Main Results:

• Bacterial persisters are crucial for the survival of infections under antibiotic stress.
• Numerous unique tolerance factors contribute to the persister phenotype in various pathogens.
• Persister cells are linked to the emergence of antimicrobial resistance variants and recurring infections.

Conclusions:

• Bacterial persisters represent a critical, yet understudied, aspect of antimicrobial resistance.
• Understanding the mechanisms of bacterial persistence is essential for overcoming treatment failures.
• Targeting bacterial persisters offers a promising avenue for developing new anti-infective strategies.