Combatting persister cells: The daunting task in post-antibiotics era

Area of Science:

• Microbiology
• Molecular Biology
• Drug Discovery

Background:

• Antibiotic resistance is well-studied, but bacterial persisters, which cause drug treatment failure through distinct mechanisms, are often overlooked.
• Persisters are phenotypic variants that survive antibiotic exposure without genetic resistance, posing a significant clinical challenge.

Purpose of the Study:

• To review the clinical significance of bacterial persisters.
• To explore the evolutionary relationships between antibiotic resistance, tolerance, and persistence.
• To summarize mechanisms of persister formation and methods for their study.

Main Methods:

• Literature review of bacterial persister cells.
• Analysis of evolutionary links between resistance, tolerance, and persistence.
• Discussion of novel findings on aggresomes in regulating bacterial dormancy.

Main Results:

• Persister cells represent a critical factor in antibiotic treatment failure, distinct from antibiotic resistance.
• Multiple redundant mechanisms contribute to the formation of persister cells.
• Aggresomes play a role in regulating the depth of bacterial dormancy.

Conclusions:

• Bacterial persisters have significant clinical implications and require further research.
• A novel therapeutic strategy is proposed: inducing deeper dormancy in persisters to create viable but non-culturable (VBNC) cells, preventing regrowth.
• Further investigation into persister biology and anti-persister therapies is warranted.