# Mechanistic insights into bacteriophage properties required for enhanced therapeutic potential at mucosal surfaces

> **NIH NIH U19** · BAYLOR COLLEGE OF MEDICINE · 2022 · $400,444

## Abstract

Project Summary
The human mucosal surface is a complex ecosystem made of bacteria, viruses, epithelial cells,
mucus, and molecules such as proteins, sugars, and other solutes whose balance is key to the
health of the host. It is also the first line of defense against invading bacteria, and a site of
colonization by diverse microbiota. Some members of this microbiota, termed pathobionts,
cause serious local and systemic infections. However, the use of antibiotics to treat these
infections is a classic Catch-22; there may temporary relief but down the road the very solution
generates a bigger version of the original problem. Whereas one may rid the environment of the
pathobiont, one also eliminates the beneficial microbiota that antagonize the pathobiont while
creating a selection that further increases rates of resistance. In addition, the destruction of the
balance of the ecosystem further predisposes that system to invasion by other pathobionts, and,
in the long run, increases the risk of infection and inflammation. There is a real need to develop
an alternative line of antibacterials that lack these limitations.
 The overall objective of this project is to discover bacteriophage, viruses that infect and kill
bacteria, that are specifically active against drug-resistant pathobionts in the complex
environment of a human mucosal surface. These phage should be specific for their bacterial
target, as well as have evolved features that promote enhanced activity in the face of the
complexity presented by such surfaces. Furthermore, should the pathobiont spread
systemically, these phage should synergize with conventional antibiotics while simultaneously
generating a steep evolutionary path for the emergence of new resistance. Using one of the
world’s largest collections of therapeutic phages and characterizing them for enhanced activity
in human mucosal biomimetics, the research program described here lays the foundation for the
development of a novel class of mucosal-active antibacterials that clear problematic pathobionts
while simultaneously maintaining balance of the native microbiota.

## Key facts

- **NIH application ID:** 10357968
- **Project number:** 5U19AI157981-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** ANTHONY W MARESSO
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,444
- **Award type:** 5
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357968

## Citation

> US National Institutes of Health, RePORTER application 10357968, Mechanistic insights into bacteriophage properties required for enhanced therapeutic potential at mucosal surfaces (5U19AI157981-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10357968. Licensed CC0.

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