Single-Cell Approach Reveals Intercellular Heterogeneity in Phage-Producing Capacities

Area of Science:

• Microbiology
• Molecular Biology
• Virology

Background:

• Bacteriophage burst size, the number of progeny virions released per infected cell, is crucial for phage replication dynamics.
• Traditionally measured at the population level, single-cell burst size and its variability remain less understood.
• Intracellular progeny accumulation duration directly influences bacteriophage burst size.

Purpose of the Study:

• To investigate bacteriophage lambda (λ) single-cell burst size mean and variance.
• To determine the impact of intracellular accumulation period on burst size and its variability.
• To explore the relationship between lysis timing, cell size, and burst size noise.

Main Methods:

• Utilized Escherichia coli lysogens with lysis-deficient λ prophages.
• Isolated single lysogens and chemically induced lysis at specific time points post-induction.
• Quantified intracellular progeny accumulation and estimated single-cell burst size mean and variance.

Main Results:

• λ phage burst size increased exponentially with lysis time, eventually saturating.
• Cell-to-cell variation in lysis timing did not significantly contribute to burst size noise.
• Burst size noise remained constant as mean burst size increased, suggesting intercellular heterogeneity in phage production capacity.

Conclusions:

• Cellular capacity for phage production, not lysis timing variation, is the primary driver of burst size noise.
• Mean burst size correlates positively with cell volume, indicating its role in phage production capacity.
• Factors beyond cell size also influence cellular capacity for phage production.