Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions

Area of Science:

• Microbiology
• Infectious Diseases
• Bacterial Physiology

Background:

• Antibiotic persisters are a small subpopulation of bacteria surviving high antibiotic concentrations.
• Persisters, alongside biofilms, contribute significantly to recalcitrant and recurring infections, leading to severe morbidity and mortality.
• Understanding persister cell formation is crucial for developing effective treatments against persistent bacterial infections.

Purpose of the Study:

• To review the clinical significance of persister cells.
• To elucidate the central role of bacterial metabolism in persister cell formation.
• To explore persister formation as an evolutionary strategy and discuss implicated response mechanisms.

Main Methods:

• Literature review focusing on bacterial metabolism, stress response, and evolutionary strategies.
• Contextualization of in vitro findings with potential in vivo conditions.
• Discussion of how advanced 'big data' tools can advance research.

Main Results:

• Bacterial metabolism, including carbon catabolite repression, sugar metabolism, and growth regulation, is central to persister cell formation.
• Persister formation is an evolutionary strategy for tolerating extended stress periods.
• In vivo conditions may create ecological niches that promote persistence, differing from in vitro models.

Conclusions:

• Persister cells pose a significant clinical challenge due to their role in persistent infections.
• Bacterial metabolism and stress response mechanisms are key targets for understanding and combating persisters.
• Future research utilizing advanced sequencing and big data tools is essential for investigating in vivo persistence mechanisms and improving clinical outcomes.