Targeting resistance at its source: identifying superspreaders of antimicrobial resistance genes in hospital ecosystems

The National Institute of Allergy and Infectious Diseases awarded the University of Virginia $795,990 on April 23, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to identify and target bacterial and genetic superspreaders of antimicrobial resistance genes in hospital ecosystems.

The research investigates mechanisms of antibiotic resistance gene transfer within hospital environments, particularly focusing on carbapenemase resistance spreading through wastewater and premise plumbing such as sink drains. The project applies genomics, epidemiology, microbiology, infection control, and network science to track resistance gene movement. Three synergistic aims drive the work: investigating gene mobility within bacterial cells through cutting-edge genomics and mathematical approaches to identify dominant transposons moving carbapenemase genes in isolates collected from patients and the environment; identifying plasmids driving carbapenemase gene transfer between bacteria; and analyzing biological factors influencing gene transfer. The ultimate goal is to disrupt antimicrobial resistance networks by targeting superspreaders, halting resistance spread at its origin.

The University of Virginia, a state-controlled public research university headquartered in Charlottesville, Virginia, serves as the recipient. Performance occurs in Charlottesville, Virginia. The award runs through March 31, 2031.

Abstract

Antibiotic resistance (AMR) is a critical global health challenge, contributing to nearly 5 million deaths annually. The rapid spread of resistance is often driven by the transfer of AMR genes via mobile genetic elements such as plasmids and transposons. Hospitals face unique challenges in controlling transmission, as AMR genes can move within and between bacterial species within patients, and the hospital environment. For more than 15 years, our hospital has worked to eliminate many species and strains that all share a single resistance gene, a carbapenemase, spreading through wastewater premise plumbing such as sink drains. Despite disinfection efforts, resistant bacteria have adapted and continued to spread resistance, underscoring the need for targeted strategies to address the source of resistance genes. This project seeks to unravel the mechanisms of antibiotic resistance gene movement and identify key bacterial and genetic superspreaders that drive transmission. Our overarching goal is to disrupt AMR networks by targeting these superspreaders, ultimately halting the spread of resistance at its origin. Our research brings together an effective expert team with knowledge of genomics, epidemiology, microbiology, infection control, and the mathematics of network science to track the spread of AMR genes in ways that were not previously possible. To achieve this, we propose three synergistic aims: first, we will investigate gene mobility within bacterial cells by combining cutting-edge genomics and novel mathematical approaches to determine the dominant transposons and mechanisms moving a carbapenemase gene in isolates that we have collected from patients and the environment. Second, we will identify plasmids that are driving carbapenemase gene transfer between bacteria. We will analyze the biological factors influencing gene transfer by combining innovative mathematical modeling with laboratory experiments. Our unique sink-drain lab, simulating hospital plumbing, provides an unparalleled environment for testing these dynamics. Lastly, we will develop predictive models of AMR gene spread by integrating genomic and epidemiological data into comprehensive models to predict AMR gene movement across bacterial communities. To demonstrate the generalizability of our approach, we will apply IT to a different class of emerging antibiotic resistance genes. This research aligns with the agency's mission by addressing a critical public health threat through innovative and actionable science. Efforts to eliminate drug-resistant bacteria using disinfectants and antibiotics have largely failed, often creating selective pressure that allows AMR to persist while killing off beneficial bacteria. By shifting the focus to the genetic elements that spread resistance, our work will lay the foundation for smarter, more effective infection control strategies. This approach has the potential to reshape how hospitals, public health agencies, and scientists combat AMR, reducing its impact on patients and preventing the emergence of even more dangerous antibiotic resistant superbugs.