Tufts Research Team Awarded Global Grant to Advance Antibiotic Discovery

A research team at Tufts University School of Medicine has been awarded a competitive international grant through the Gates Foundation’s Global Grand Challenges program to accelerate the discovery of new antibiotics against multidrug‑resistant infections.

The project is led by Joan Mecsas, PhD, Professor of Molecular Biology and Microbiology, in collaboration with Bree Aldridge, PhD, Professor of Molecular Biology and Microbiology and of Biomedical Engineering, and Ralph Isberg, PhD, Professor of Molecular Biology and Microbiology. The team was selected as one of 18 projects funded through the Gram‑Negative Antibiotic Discovery Innovator (Gr‑ADI) consortium, a first‑of‑its‑kind global effort to transform early‑stage antibiotic discovery for Gram‑negative bacteria. The consortium is jointly supported by the Gates Foundation, Novo Nordisk Foundation, and Wellcome.

Selected from a pool of more than 500 proposals, the Tufts project, Tissue‑Based Target Profiling to De‑Risk Drug Discovery for Multidrug‑Resistant Klebsiella, targets one of the most urgent threats in global public health: antimicrobial resistance (AMR) caused by Gram‑negative bacteria.

A New Way to Identify Drug Targets

One of the main problems the Tufts team is trying to solve is that Klebsiella pneumoniae is highly variable from strain to strain. This genetic diversity, known as genetic heterogeneity, means that a novel drug that works well against one strain may not work against another. At the same time, the bacteria can live in different parts of the body, such as the lungs, intestines, or bloodstream. Each of these tissues provides a unique environment, and bacteria can behave differently and respond differently to drugs depending on where the infection occurs.

“This research fills a major gap in the field,” said Mecsas. “Here we will develop and use tools that specifically target the bacteria in their infectious environments and in places where they hide out. We hope to identify where they are most vulnerable in these places.”

The project focuses on improving how new antibiotics are developed to fight multi-drug resistant Klebsiella pneumoniae, which can cause serious illnesses such as pneumonia, bloodstream infections, and urinary tract infections.

To address the limitations of conventional laboratory models, the Tufts team will develop portable, tissue‑specific systems that more accurately reflect how Klebsiella behaves in real infections. Alongside these models, they will create a genetic screening platform to identify bacterial genes and biological pathways that remain vulnerable across many strains and tissue environments.

“We want to develop and make available innovative tools to accelerate screening of novel therapeutics for ESKAPE pathogens and other MDR bacteria,” Mecsas said, referring to a group of pathogens responsible for a large proportion of hospital-acquired infections worldwide.

By combining tissue‑based modeling with genetic target profiling, the team aims to generate a robust set of high‑confidence drug targets. This information can help guide the development and prioritization of new antibiotics before they enter costly later‑stage development, reducing risk and increasing the likelihood of success.

A Tradition of Contribution to AMR Research

The award reflects Tufts University School of Medicine’s long-standing leadership in infectious disease and antimicrobial resistance research, anchored by the Stuart B. Levy Center for Integrative Management of Antimicrobial Resistance at Tufts (Levy CIMAR). This legacy dates back to the 1970s, when Tufts scientist Stuart Levy and his colleagues made a landmark discovery while studying resistance to tetracycline. They were the first to demonstrate that some bacteria can actively pump antibiotics out of their cells using energy—a mechanism now known as antibiotic efflux.

Levy CIMAR continues that legacy as a hub for interdisciplinary research on resistant and emerging pathogens, encompassing bacterial pathogenesis, host–pathogen interactions, antimicrobial tolerance, and treatment failure. The research supported by this award will draw on Levy CIMAR’s expertise and resources, reinforcing its role as a catalyst for innovation in the field.

The project also aligns closely with existing Tufts research strengths and collaborative initiatives. Mecsas noted the strong synergy with ongoing efforts within the Tufts Infection and Immunity Initiative and the Transplant, Immunity, and Infection pillar of the Tufts University–Tufts Medicine Research Enterprise.

Together, this work and its institutional context reflect the School of Medicine’s depth and continuity in antimicrobial resistance research—combining fundamental microbiology with clinically and globally relevant approaches to address one of the most urgent challenges in infectious disease.