About this Event
35 East 12th Street, Holland, MI 49423-3605
View map
TITLE: "A novel chemical design platform for developing selective antibiotics against resistant, pathogenic bacteria in mixtures"
ABSTRACT: The rise of β-lactam resistance necessitates new strategies to combat bacterial infections. I purposefully engineered the β-lactam prodrug AcephPT to exploit β-lactamase activity to selectively suppress resistant bacteria producing extended-spectrum-β-lactamases (ESBLs). Selective targeting of resistant bacteria requires avoiding interaction with penicillin-binding proteins, the conventional targets of β-lactam antibiotics, while maintaining recognition by ESBLs to activate AcephPT only in resistant cells. We show AcephPT selectively suppresses gram-negative ESBL-producing bacteria in clonal populations and in mixed microbial cultures, with effective selectivity for both lab strains and clinical isolates expressing ESBLs. Time-course NMR experiments confirm hydrolytic activation of AcephPT exclusively by ESBL-producing bacteria. In mixed microbial cultures, AcephPT suppresses proliferation of an ESBL-producing strain while sustaining growth of β-lactamase-non-producing bacteria, highlighting its potential to combat β-lactam resistance while promoting antimicrobial stewardship.
BIO: Addison Duda earned a BS in Chemistry from Hope College in 2019. While at Hope, his research in Prof. Jason Gillmore’s group was on optimizing Sonogashira coupling conditions to be used for polymerization of azo dyes. Additionally, Addison was on Dance Marathon’s Dream Team, helping the team to raise nearly $1 million for Helen DeVos Children’s Hospital of Grand Rapids during his three-year involvement with the group. Following graduation, he worked as a Research Associate with Dr. Tom Guarr at Michigan State University Bioeconomy Institute synthesizing derivatized heterocycles for battery redox shuttles and linked heterocyclic systems for nonaqueous redox flow batteries. While there, he applied and developed a hypervalent iodine mediated, oxidative diaryl coupling reaction method for preparation of tetrasubstituted carbazoles, which was later submitted as a provisional patent with MSU. Addison is currently a graduate student at Duke University pursuing a PhD in Chemistry, with a focus in Chemical Biology, and has completed a graduate certificate in Innovation and Entrepreneurship. He will defend his dissertation later this Spring. Addison works in the lab of Prof. Kathy Franz developing β-lactam prodrugs that selectively target resistant, pathogenic bacteria by hijacking the β-lactamase resistance enzymes those pathogens harbor; these molecules are being considered for patent by Duke University. Addison has also been an elected chair member for the Duke Chemistry Department’s outreach program and alumni engagement program to provide science demos at schools in the greater RTP area and to facilitate the organization of alumni networking events for his fellow colleagues. Addison’s involvement with Duke University will continue after graduation as he serves as a Graduate-Alumni member of Duke’s Trinity Board of Visitors to help the Deans and the largest donors of Duke University enhance academic excellence for students in Arts and Sciences. Addison is currently searching for the next place to call home as a postdoctoral researcher, aiming to continue to hone the skills he has developed at Hope, MSU, and Duke to become a strong independent academic scientist.
Event Details
See Who Is Interested
0 people are interested in this event
