Mechanisms by which ICP3 Overcomes Vibrio cholerae Phage Defenses

PROJECT SUMMARY
Bacteriophages (phages) are bacteria-specific viruses. Phages play a major role in the life cycle and evolution
of Vibrio cholerae, the bacteria that causes cholera. Despite the presence of many V. cholerae-specific phage
types in the environment, only three types, ICP1, ICP2 and ICP3, are commonly found at high concentrations
in the watery diarrhea shed by cholera patients. Thus, these three phages are special for their ability to survive
in the human intestinal tract, where they replicate on and kill V. cholerae. Of these phages, ICP3 is the most
virulent in terms of its ability to kill V. cholerae. The emergence of resistance to ICP1, ICP2 and to other phages
is frequent in V. cholerae, but, for unknown reasons, resistance to ICP3 is exceedingly rare. This makes ICP3
of great interest for use as a product to treat or prevent cholera. The use of phages for therapy or prevention of
bacterial infections is gaining broad interest due to the emergence of multidrug resistance in many bacterial
pathogens, including V. cholerae. To gain a better understanding of ICP3’s virulence and lack of emergence of
host resistance, in this exploratory project we will delete each of the approximately four dozen accessory genes
of ICP3 and test their roles in circumventing the phage defense systems of V. cholerae. Addionally, we will
identify the cognate host phage defense genes in V. cholerae for each ICP3 accessory gene. The results will
shed much light on ICP3's special abilities, and will encourage the development of ICP3 into a product for use
in combatting cholera.

Grant Number: 5R21AI181039-02
NIH Institute/Center: NIH
Principal Investigator: Andrew Camilli