Phages produce persisters.

Area of Science:

• Microbiology
• Bacteriology
• Virology

Background:

• Bacteriophages (phages) are a primary threat to bacterial populations.
• Bacterial survival of phage infection is typically attributed to mutations conferring resistance or active defense systems.
• An alternative survival strategy, the persister state, involves transient dormancy without genetic mutation, previously observed under antibiotic stress.

Purpose of the Study:

• To investigate bacterial survival mechanisms against lytic phage infection.
• To determine if bacteria form persister cells during phage attack, similar to antibiotic stress.
• To characterize the genetic and physiological state of bacteria surviving phage infection.

Main Methods:

• Isolation of surviving bacteria from plaques of virulent phages (T2, T4, lambda cI mutant).
• Genome sequencing of surviving bacterial populations to identify genetic mutations.
• Assessment of phage sensitivity and antibiotic survival in isolated bacterial cells.
• Experimental validation using T2 phage and pre-established persister cell cultures.

Main Results:

• Bacteria survived phage infection through both mutation-driven resistance and non-mutational persistence.
• Mutations conferring high-level phage resistance (e.g., mucoidy) were observed in T4 and lambda phage infections.
• A significant subpopulation survived T2 phage infection without detectable mutations, retaining wild-type phage sensitivity and antibiotic resistance.
• Persister cells exhibited a 137,000-fold higher survival rate against T2 phage compared to exponentially growing cells.
• Persister cell formation was also observed in Klebsiella pneumonia and Pseudomonas aeruginosa under phage treatment.

Conclusions:

• Bacteria employ both genetic mutation (resistance) and physiological dormancy (persistence) to survive lytic phage infections.
• Persister cell formation represents a significant, previously underappreciated survival strategy against phages.
• The findings suggest that dormancy allows bacteria more time to activate or develop phage defense mechanisms.
• This study broadens the understanding of bacterial resilience in the face of phage predation and potential therapeutic applications.