Skip to main content
Global One Health Academy

GCAP Antimicrobial Resistance Seed Grants Awarded

September 30, 2024

Over the summer the Global One Health Academy launched a new initiative – the Grand Challenges Addressing Program (GCAP) – to address wicked problems that demand an interdisciplinary approach. The first GCAP is targeting the silent pandemic of antimicrobial resistance (AMR) at the human-animal-plant-environment interface. To accelerate this effort, GOHA launched and awarded seed grants for interdisciplinary AMR research. Learn more about the five funded projects below!

Launch Projects

Launch Projects are awarded to those that will lead to external grant submission within a short time window.

Decoding antimicrobial resistant organisms’ colonization through One Health interdisciplinary research

  • PIs: Cristina Lanzas (CVM), Casey Theriot (CVM), Josh Fletcher (CVM), Ben Callahan (CVM), Alun Lloyd (COS), Frank Scholle (COS), Reza Ghiladi (COS), Nathan Crook (COE), and Angela Harris (COE)
  • Abstract: Antimicrobial resistant organisms (ARO) are a significant public health threat worldwide. Colonization with ARO is a necessary precursor to infection, but it often occurs asymptomatically and is not detected unless infection occurs. This project aims to establish an interdisciplinary team to advance the understanding of ARO colonization through a One Health approach, integrating human, animal, and environmental health perspectives. Our research team combines the experiences of nine experts in infectious disease modeling, microbiome, microbiology, synthetic biology, bioinformatics, microbial ecology, environmental engineering, and chemistry, and will focus on two key objectives: 1) To produce a comprehensive review/perspective paper on ARO colonization that identifies key research gaps and establishes a collaborative framework for future studies; and 2) To develop an NIH R01 proposal based on the application of multi-scale models that integrate within-host dynamics, population-level transmission, and environmental factors influencing ARO colonization, followed by the establishment of an animal model to parametrize and validate the model, and the in-silico evaluation of the impact of pathogen load reduction strategies on the colonization and transmission of ARO. Our integrative perspective will lead to the development of comprehensive strategies for ARO detection, management, and decolonization. The outcomes of this project will inform better risk assessments for ARO, guide novel interventions targeting colonization, and contribute to the reduction of the burden of ARO in human, veterinary, and environmental health.

Development of novel antimicrobial materials for infection prevention

  • PIs: Reza Ghiladi (COS) and Richard Spontak (COE)
  • Abstract: Microbial infections are one of the most prevalent health challenges of our time. Despite advances made over the years to develop antimicrobial agents, emerging pathogens and resistant strains mean there is a significant need to identify new agents and innovative approaches with which to treat, and more importantly, prevent microbial infections. While the COVID-19 pandemic illustrated the acute need for materials designed to keep healthcare staff and patients safe from novel pathogens, the 1.7 million healthcare-associated infections (HAIs) that occur annually in the US, and which cause upwards of 100,000 deaths each year, demonstrate the chronic problem associated with pathogen transmission. To address the lack of options for simple and cost-effective self-disinfecting materials for use in healthcare settings, here we propose to study anionic polymers that are inherently antimicrobial, without the need for any additives or inclusion of antimicrobial agents. These thermoplastic elastomeric polymers reduce the pH at the localized pathogen:surface interface to as low as ~0.8 due to their sulfonated styrenic midblock, resulting in rapid pathogen inactivation. Our preliminary results demonstrate that these polymers are highly effective at inactivating a range of Gram-positive and negative drug-resistant bacteria, enveloped (including coronaviruses) and non-enveloped viruses, and fungi, all in just minutes. By increasing the scope of polymers that employ this novel mechanism of action, this proposal will provide the necessary studies to translate ‘pH-dynamic’ polymers for use in self-disinfecting materials as a new tool against pathogen transmission relevant to HAIs, with broader applicability to the agricultural and livestock sectors.

Pilot Projects

Pilot Projects are awarded to those involving new collaborations and/or new research directions.

Sunny-day flooding and AMR organisms: filling a ONE health knowledge gap to understand human health risks posed by rising sea levels

  • PIs: Angela Harris (COE), Natalie Nelson (CALS), Katherine Anarde (COE), and Benjamin Callahan (CVM)
  • Abstract: Rising global sea levels, caused by glacier mass loss and climate change, are negatively affecting coastal communities through the increase in severity and frequency of inundation of seawater from high tides into stormwater networks. This phenomenon, called “sunny day flooding”, can trigger the spread of fecal bacteria and antimicrobial resistance (AMR) genes, which is an increasing global health threat. AMR bacteria represent a critical risk to environmental, animal, and human health as they render antibiotic treatments ineffective. This study aims to assess the presence of AMR bacteria present in sunny day floodwaters and impacted soils to support the evaluation of the currently unknown risk these events pose to coastal communities in North Carolina. Floodwater sampling will occur at Carolina Beach, North Carolina during 3 different field campaigns, capturing both spatial and temporal variability in contamination levels. Through the use of mixed culture sequencing and metagenomics, we will be able to genetically characterize the AMR bacteria to better understand the risks they pose and the sources of contamination. This exploratory study seeks to provide insights to AMR bacteria contamination levels, transport processes, and potential health hazards and to inform future studies to better understand exposures and risks as well as management and mitigation strategies to protect human, animal, and environmental health.

GOHA STARS: Student-driven Tiny earth Antimicrobial Resistance Solutions

  • PIs: Stephanie Mathews (COS), Nathalie Lavoine (CNR), and Michael Taveirne (COS)
  • Abstract: According to the 2019 CDC report on Antimicrobial Resistance (AMR) in the United States, there are more than 2.8 million AMR infections and 35,000 associated deaths each year. The 2022 report showed that hospital-onset infections of AMR bacteria increased by 20% annually. This health crisis requires action; efforts are needed to prevent infection but also to find novel solutions to treat, and ultimately prevent AMR infections. Tiny Earth is a Course-Based Undergraduate Research Experience (CURE) that utilizes a student-led approach to novel antimicrobial discovery. Every semester, NC State University Tiny Earth students isolate, identify, and characterize antimicrobial producing bacteria from soil. Students work towards identifying the antimicrobial compounds and assessing its effectiveness against surrogate pathogens to clinically relevant AMR bacteria. This proposal aims to leverage the resources of Global One Health Academy and student discovery to expand the scope of the Tiny Earth course to include genomic characterization of bacterial isolates, identification and purification of antimicrobial compounds, and suitable application of these antimicrobial agents. Successful completion of these objectives will support the development of new CURE courses across the University, allowing students to address the AMR crisis from soil to clinical applications.

Machine Learned Synergistic Antibiotic Combinations to Expand Access to Therapies

  • PIs: Kaixiong Zhou (COE), Albert Keung (COE), and Yi-Hui Zhou (COS)
  • Abstract: The effectiveness of antibiotics is undermined by antimicrobial resistance (AMR) due to widespread antibiotic overuse. The development of antibiotics has not kept pace with the evolution of pathogens – There is no new class of antibiotics that has been developed and applied to clinical use as new medicines for decades. One promising solution is to adopt drug combination therapy to reduce the frequency of antimicrobial resistance. However, the roadway to discover antibiotic combinations for bacterial infection is still elusive because of the immense search space and unclear drug synergistic mechanism. To bridge this gap, this project aims to develop a high-throughput drug combination screening framework based on machine learning to recognize the synergistic effects of drug combinations, facilitating in-silico therapy discovery and wet-lab verification. Specifically, we propose to design a generalizable and trustworthy screening platform by integrating robust machine learning algorithms and interpretable techniques. While a recipe of robust neural network training aims to enhance prediction accuracy of large-scale drug combinations, interpretable learning sheds insight into how the drug substructures synergizes towards inhibiting the target microbes. The project will result in the dissemination of robust and interpretable DNN models that the broader biomedicine communities can use in real-world antibiotic combination discovery.