Fighting drug-resistant bacteria with AI-designed nanomaterials

UIC College of Engineering faculty member Lisa Stabryla is one of only four researchers from the Chicago area to receive a What If…? Award for Creative Medical Research from the Science Philanthropy Alliance.

The What If…? Awards Program is a new philanthropic initiative from the Science Philanthropy Alliance to catalyze innovative early-stage research in biomedical and health science. The program supports high-risk, high-reward projects that pose bold "What if?" questions in areas ranging from neurodegenerative diseases and cancer to artificial intelligence in clinical care and antimicrobial resistance.

Stabryla, assistant professor of civil, materials and environmental engineering, received $500,000 in pilot funding over two years for her project. The question she's investigating: What if we could fight drug-resistant bacteria with AI-designed nanomaterials?

Antimicrobial resistance is making wound infections increasingly challenging to treat, underscoring the need for alternatives to conventional antibiotics. Metal and metal-oxide nanoparticles, especially silver-based formulations, called AgNPs, are a promising class of antimicrobials already used in wound dressings and medical device coatings.

"Our preliminary findings indicate that clinically relevant bacteria can adapt to and develop resistance against specific AgNP designs. Yet, our work also shows that variations in AgNP design can dramatically enhance antimicrobial efficacy," said Stabryla, director of the Stabryla Lab at UIC. "These results highlight the urgency and the opportunity: Nanoparticle properties are tunable, but the relationships between design parameters, antimicrobial performance and evolutionary outcomes in bacteria remain poorly understood."

Stabryla and her team plan to rationally design next-generation, "evolution-resilient" nanoparticles by linking size, shape and other physicochemical geometric/morphological properties to antimicrobial efficacy and bacterial adaptation pathways. They will integrate laboratory evolution under controlled conditions, whole-genome sequencing and a machine learning-based generative design model to identify nanoparticle designs that maximize antimicrobial activity while minimizing or redirecting the evolution of resistance.

This generative approach, led by Jida Huang, UIC assistant professor of mechanical and industrial engineering, is essential to efficiently explore this vast design space and navigate thousands of possible nanoparticle designs that cannot be tested experimentally to identify the most promising candidates. Outside of engineering, the team includes Dr. William Ackerman, research assistant professor in the College of Medicine, and Kyunghee Han, associate professor of mathematics, statistics and computer science.

"Rather than focusing on optimization of a single material in isolation, this approach will set the stage for conceptualizing nanoparticles as tools that can be designed to work together as part of a larger engineered system," Stabryla said. "By deliberately combining different nanoparticle designs, we can tune how they work together - using complementary or opposing effects - to create 'evolutionary traps' that reduce the chances of bacteria adapting and developing resistance.

"Promising candidates will be chemically synthesized, tested against pathogenic bacteria and incorporated into a prototype polymeric nanocomposite coating for future clinical application," she added. "The outcome of this work could accelerate antimicrobial materials discovery and enable new infection-control technologies that improve patient safety and reduce the burden of antimicrobial resistance."

The Science Philanthropy Alliance, founded in 2014, advises philanthropists on giving to discovery science in a wide range of disciplines, in order to advance scientific discovery for the benefit of humanity.

- David Staudacher, UIC College of Engineering