Single-cell Studies of Phage Decision Making and Infection Dynamics

Bacterial viruses (bacteriophages) are the most abundant biological identities on earth. Quantitative studies of their infection cycles can elucidate the underlying mechanisms of the infection processes, shed important insight on how other viruses operate in higher organisms and help develop novel antibacterial strategies. In my talk, I will share two stories of different phages. In the first story, I will discuss our recent high-resolution studies of a paradigmatic system of cell-fate determination, the bacterium E. coli and its virus – phage lambda. Our studies suggest that individual phages vote for lysis or lysogeny and exhibit different interactions within the cell which include cooperation during lysognization, competition against each other during lysis, and confusion or coexistence between the two pathways. In addition, we found that phage DNAs establish separate subcellular compartments (‘ph(f)actories’) inside the cell which sustains heterogeneous viral development in single cells. In the second story, I will discuss our recent findings of ssRNA phages. We found that during the course of infection, ssRNA phage MS2 or Qbeta can detach the F-pilus of E. coli which is used for conjugation. This pilus-detachment feature can be thought of as a novel mechanism for superinfection exclusion and ssRNA phages can be engineered to remove retractile pili (virulence factors) thereby to disarm pathogens.