The macrophage-bacterium mismatch in persister formation

Area of Science:

• Microbiology
• Cell Biology
• Immunology

Background:

• Antibiotic persisters are bacterial subpopulations that survive antibiotic treatment despite lacking resistance mechanisms.
• Intracellular antibiotic persisters, residing within host cells, are increasingly recognized, with bacterial stress responses playing a key role.
• The precise conditions driving the formation of stress-induced persisters within a seemingly uniform intracellular environment remain unclear.

Purpose of the Study:

• To review current knowledge on intracellular antibiotic persisters.
• To explore the roles of host cell and bacterial heterogeneity in persister formation.
• To propose a model explaining stress-induced persister emergence.

Main Methods:

• Literature review and synthesis of existing research on antibiotic persisters.
• Conceptual analysis of macrophage functional heterogeneity.
• Conceptual analysis of bacterial phenotypic heterogeneity.

Main Results:

• Macrophage functional heterogeneity can influence the intracellular environment.
• Bacterial phenotypic heterogeneity affects their ability to survive and replicate intracellularly.
• A mismatch between macrophage permissiveness and bacterial preparedness is proposed as a driver for persister formation.

Conclusions:

• Host cell and bacterial heterogeneity are critical factors in the development of intracellular antibiotic persisters.
• The interplay between macrophage permissiveness and bacterial preparedness offers a framework for understanding stress-induced persister formation.
• Further research into these heterogeneities could reveal new therapeutic strategies against persistent infections.