Bacteriophages (phages) are viruses that specifically infect bacteria. Phages have been shown to play important roles in the life cycle of many bacterial pathogens, particularly water-borne pathogens that cause gastrointestinal tract infections. For example, the lysogenic phages, which integrate their DNA into the host genome, can play positive roles by providing virulence factors such as toxins that enhance the virulence of their host bacterium. Other phages known as lytic or virulent phages can play negative roles by infecting and killing their host bacterium, thus reducing the number of the pathogen below the threshold needed to cause disease. Vibrio cholerae is a water-borne pathogen that infects the small intestine to cause the severe diarrheal disease cholera. Although it is well known that a lysogenic phage called the CTX phage enhances virulence by providing the genes encoding cholera toxin, our recently published and preliminary data indicate a pervasive negative role for several virulent phages that are commonly found in cholera endemic areas around the Bay of Bengal. These virulent phages appear to reduce the virulence, transmission, and potentially dissemination of V. cholerae. However, there is much we still do not know about these phages in terms of their ability to kill V. cholerae in the environment, to inhibit fecal-oral transmission of cholera such as occurs frequently within households, and their impact on the emergence of new V. cholerae strains. In this project, we will investigate each of these areas. In addition, we will study the importance of another lysogenic phage called Kappa in the virulence of V. cholerae.

Public Health Relevance

Bacteriophages (phages) are believed to reduce the density of bacterial pathogens in their environments and therefore transmission of disease, and also to impact the evolution of bacteria, perhaps contributing to the emergence of new strains. Yet, there is scant evidence to support these claims. To reveal if and how phages can play these important roles, we will investigate the impact of four phages that are commonly associated with Vibrio cholerae on bacterial virulence, transmission, and strain evolution.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI055058-17
Application #
10064987
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Baqar, Shahida
Project Start
2003-05-15
Project End
2025-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
17
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Tufts University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111