# Host Targeted Therapy for Drug Resistant Salmonella and Francisella infection

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $1,043,412

## Abstract

Abstract
 The formation of antibacterial drug resistance is a public health crisis and has led to increaseing
healthcare costs and even death. Drug resistance can occur when an antibiotic directly kills a pathogen or
prevents its growth because of selective pressure. This phenomena has generated various multi-drug resistant
bacterial species that are a global public health concern.
 Most antibacterial therapeutics target the pathogen in an attempt to clear infection. However, more
recently the concept of antibacterial therapeutics that target host specific pathways has been developed. These
pathways can potentially prevent infection, virulence, replication, and proliferation. Therapies that target these
pathways could potentially treat traditional antibiotic resistant strains. Additionally, targeting the host instead of
the pathogen could prevent the development of drug resistance because the therapy could activate pathways
that fight resistance and activate the host’s defense mechanisms. Futhermore, because many pathogens take
advantage of similar pathways, there is a potential for developing therapies that target a broad-spectrum of
pathogens.
 We were one of the first groups to use a host-targeted therapeutic (HTT) for the treatment of a pathogen
that is considered a Threat Level of Serious by the CDC. This HTT does not work directly on intracellular
pathogens but instead targets host cell promoting pathways that result in clearance of the pathogen. Additionally,
this HTT has broad-spectrum activity against pathogens including a NIAID Category A class pathogen. We have
both in vitro and in vivo data showing activity and increase in survival. In order to increase activity we have
encapsulated this compound in a novel biomaterial that is acid sensitive. This acid sensitivity allows for the
intracellular release of encapsulated cargo. Our preliminary data shows that encapsulation of the HTT drastically
enhances the efficacy of the compound compared to non-encapsulated form.
 In this proposal, we propose on performing medicinial chemistry on our HTT to develop a compound with
increased activity. We will formulate this compound in our novel polymeric particles for both in vitro and in vivo
testing. We will perform various biological assays to determine activity of optimized compounds. In order to do
this, our proposal is a partnership between the University of North Carolina, National Taiwan University, and the
Research Triangle Institute (RTI). This partnership will be invaluable in obtaining an optimized HTT compound
that has activity against a broad spectrum of pathogens as it incoporates academic researchers in the field and
RTI’s experience with drug development.

## Key facts

- **NIH application ID:** 9901429
- **Project number:** 5R01AI125147-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Kristy M Ainslie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,043,412
- **Award type:** 5
- **Project period:** 2016-04-22 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9901429

## Citation

> US National Institutes of Health, RePORTER application 9901429, Host Targeted Therapy for Drug Resistant Salmonella and Francisella infection (5R01AI125147-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9901429. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*