# Bacteriophage diversity, dynamics, function, and exploitation

> **NIH NIH R35** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $454,027

## Abstract

Bacteriophages are the most numerous biological entities on the planet. The phage population is enormously
dynamic, replacing itself through infection and reproduction every few days, and may be more than three billion
years old. Not surprisingly, they are enormously diverse genetically, although this diversity remains ill-defined
and only an extremely small part of the phage population has been genomically explored.
Bacteriophages play prominent roles in the environment, in human health, and in biotechnology. They are
implicated in many bacterial diseases by coding for toxins, and modulate bacterial physiology in a variety of
ways. Their diversity is generated in part by the highly dynamic microbial community in which there is
enormous selective pressure for bacteria to survive the constant onslaught of viral infections, and for the
phages to co-evolve by mutating to infect new bacterial hosts or evolving counter-defense systems that
overcome resistance. Among the defense systems that bacteria use to fight off phage infection are restriction-
modification and CRISPR-Cas systems, both of which have played revolutionary roles in biotechnology and
genome engineering. The huge impact of these derives in part from their extraordinary efficiency and
specificity, the consequences of three billion years of highly dynamic evolution.
The growing problem of widespread antibiotic resistance by bacterial pathogens presents a substantial global
health risk. Addressing this requires innovative strategies for new therapeutic approaches, and an aggressive
search for new antimicrobial agents. The prospects of bacteriophage therapy have been contemplated for
nearly 100 years, but has not found widespread use in the US. Diseases caused by pathogens in the phylum
Actinobacteria, including tuberculosis and NTM infections of Cystic Fibrosis patients, are notable public health
challenges, but any prospects for therapeutic phage interventions requires an understanding of the
determinants of phage host range and the mechanisms and specificity of phage resistance.
A large collection of over 13,000 phages infecting Actinobacterial hosts, 2,500 of which are completely
sequenced, provide a powerful resource for investigating phage diversity, phage genome evolution, phage host
range, bacterial-phage dynamics, and genetic and clinical tools for tuberculosis and NTM infections. Many of
these phages are temperate, and code for defense systems that are prophage-expressed and inhibit the
infection of lysogens by different (i.e. heterotypic) phages. These defense systems are highly varied and most
of the genes do not have bioinformatically predicted functions. Defense is often specific for a few subset of the
phages, but the mechanisms of targeting is not known.
The characterization of phage diversity, evolution, dynamics, and resistance will facilitate the development of
new diagnostic, preventative, and therapeutic approaches for bacterial infections.

## Key facts

- **NIH application ID:** 9908115
- **Project number:** 5R35GM131729-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Graham F. Hatfull
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $454,027
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908115

## Citation

> US National Institutes of Health, RePORTER application 9908115, Bacteriophage diversity, dynamics, function, and exploitation (5R35GM131729-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9908115. Licensed CC0.

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