# Subproject 3 New Approaches to Treatment and Prevention of Antibiotic Resistant Infection

> **NIH NIH P01** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2020 · $408,302

## Abstract

Summary 
Antibiotic resistance is an acute problem in US hospitals, and threatens every branch of medicine as 
currently practiced. Antibiotic resistance is now even a national security concern. Staphylococcus 
aureus (esp. MRSA) and the enterococci (esp. VRE) are among top causes of hospital infection that 
are especially difficult to treat, because of multiple drug resistances and intrinsic hardiness. This 
proposal, in collaboration and synergy with all other subprojects, attempts to respond to the national 
challenge by building on advances made in the previous period of support, and focusing those 
resources sharply on advancing tangible solutions to this crisis. Our overarching goals are to 
improve the utility of antibiotic classes that currently exist, and to explore new therapeutic paradigms 
for multidrug resistant infection. To achieve this goal, in this Subproject, we will pursue 2 Specific 
Aims: 1) Identify impediments in MRSA/MSSA and VRE/VSE to antibiotic activity, and 2) Explore a 
new paradigm for VRE infection prevention and treatment – Gut ecology management. This project 
takes advantage of cutting-edge technologies and unique assets, including a crowd sourced strain 
collection, to obtain new information from which new and better approaches for preventing and 
treating multidrug resistant MRSA and VRE infections can be designed. We have pioneered the 
application of comparative genomics to understand the origin and spread of antibiotic resistances 
among enterococci; showing in the previous period, that anthropogenic factors such as the 
urbanization of humans and the application of antibiotics in unprecedented levels, has driven their 
evolution; and in collaboration with other subprojects, applied Tn-seq, to identify genes required for 
S. aureus growth in vitro and in vivo as well as new drug targets. Each has been precedent-setting 
in application to staphylococci and enterococci. These technologies now will be used to identify 
impediments to target inhibition by antibiotics, and to inform the design of new antibiotics and 
antibiotic potentiators. Further, a new treatment paradigm will be explored for prevention of VRE 
colonization and infection. These results will provide critical information for optimizing the design of 
new drugs and antibiotic potentiators; and new tools for improving the ecological management of 
patients to reduce the likelihood and numbers of multidrug resistant infections. We believe this data 
will be of substantial value in directly addressing the antibiotic resistance crisis that now exists.

## Key facts

- **NIH application ID:** 9996468
- **Project number:** 5P01AI083214-13
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Michael S Gilmore
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $408,302
- **Award type:** 5
- **Project period:** 2009-09-01 → 2022-02-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996468

## Citation

> US National Institutes of Health, RePORTER application 9996468, Subproject 3 New Approaches to Treatment and Prevention of Antibiotic Resistant Infection (5P01AI083214-13). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9996468. Licensed CC0.

---

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