Excellence in Research: Unraveling Mechanisms of Host-Pathogen Conflict Using Caenorhabditis elegans and Environmental Klebsiella pneumoniae

Antimicrobial resistance is one of the most significant biological challenges of the 21st century, threatening human health, food systems, and environmental sustainability. Although resistant bacteria are commonly studied in hospitals and clinical settings, natural and human-impacted environments are increasingly recognized as important reservoirs where resistance and virulence traits emerge and evolve. However, little is known about how environmental bacteria interact with host organisms or how ecological pressures shape the evolution of traits that enable pathogens to survive, colonize hosts, and resist antimicrobial treatment. This project will advance fundamental understanding of the biological processes that drive pathogen adaptation in environmental settings. The research will provide new insights into host–microbe interactions, microbial evolution, and the ecological dimensions of antimicrobial resistance. This project is led by an investigator at Fayetteville State University (FSU) in collaboration with a co-PI at the University of North Carolina Wilmington (UNCW). The partnership will strengthen research and training capacity in microbial genomics, host–pathogen biology, and computational analysis at FSU through the development of new experimental and analytical workflows, cross-institutional mentorship, and hands-on research opportunities for undergraduate students. By engaging students in STEM, the project will contribute to workforce development in the biological sciences while fostering interdisciplinary training at the interface of microbiology, genomics, organismal biology and environmental health. By improving understanding of how environmentally derived pathogens evolve and interact with hosts, the project contributes to the national interest by advancing scientific knowledge and promoting the long-term health, prosperity, and welfare of society. This project investigates how environmental strains of Klebsiella pneumoniae, an opportunistic bacterial pathogen, interact with host defense systems and evolve traits associated with antimicrobial resistance and virulence. The research tests the hypothesis that competition for iron between host and pathogen is a key factor influencing bacterial colonization and pathogenicity. Environmental K. pneumoniae isolates will be collected from wastewater and agricultural settings and characterized using genomic, phenotypic, and functional analyses. The nematode Caenorhabditis elegans will serve as a model host for examining innate immune responses and host genetic pathways involved in nutritional immunity. The project will evaluate bacterial virulence traits, including iron acquisition systems and biofilm formation, and will use functional genomics approaches to investigate the contribution of specific bacterial genes to host–pathogen interactions. By integrating environmental microbiology, microbial genomics, and experimental host–pathogen biology, this research will generate new knowledge about the evolutionary and molecular mechanisms that shape antimicrobial resistance and virulence in environmental pathogens. Collectively, the project will advance fundamental understanding of how environmental bacteria adapt to host-associated environments, provide insight into the ecological and evolutionary processes that influence pathogen emergence, and establish sustainable research infrastructure and collaborative networks that support continued innovation in environmental microbiology, organismal biology and genomic science. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.