# Investigating nanobodies to target multidrug resistant bacterial pathogens

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $686,587

## Abstract

Project Summary.
While rates of antibiotic resistance bacterial infections continue to rise, our development of new antimicrobials
has stagnated. The failure of traditional small molecule leads to restock are arsenal demands the development
of alternative approaches to prevent our slide back to the pre-antibiotic medical era. Antimicrobial peptides are
highly effective against multidrug resistant pathogens but have poor pharmacological properties hindering their
in vivo use. Antibodies have excellent pharmacological properties but generally lack direct antimicrobial action,
which limits their therapeutic use in treating infection, especially in immune compromised populations most at
risk for multidrug resistant infection. The objective of this proposal is to develop a new therapeutic paradigm
that joins the direct action of antimicrobial peptide antibiotics with the benefits of antibody structure in a single
antimicrobial agent. To develop this new modality we are leveraging the unique qualities of variable heavy
chain domain of Camelid heavy chain antibodies, known as a VHH or nanobody. Supported by a high-
throughput approaches for lead antimicrobial nanobody identification we have developed, this new paradigm
takes advantage of the benefit of direct antimicrobial peptide activity while providing a modular way to multiplex
peptide action in a pharmacologically beneficial nanobody backbone structure. Our approach has the ability to
identify both broad spectrum and target antimicrobials to selectively eliminate invading pathogens.
Furthermore, our approach has the future potential to utilize immune functions for enhanced pathogen
clearance. This proposal offers a quantum leap forward in anti-infective research. Completion of the planned
work is expected to have a positive translational impact by introducing a new direction in immune based anti-
infective therapy and new high-throughput tools for lead antimicrobial nanobody discovery, both of which will
support the fight against antibiotic resistant bacteria.
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## Key facts

- **NIH application ID:** 10225294
- **Project number:** 5R01AI148419-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Bryan William Davies
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $686,587
- **Award type:** 5
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225294

## Citation

> US National Institutes of Health, RePORTER application 10225294, Investigating nanobodies to target multidrug resistant bacterial pathogens (5R01AI148419-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10225294. Licensed CC0.

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