Spring 2020 Seminars

 

Lunch at 12 PM (Grote 403)/Seminar at 3 PM (Grote 411, Presentation 3-3:45 PM & Question Sesssion 3:45-4:00 PM)

 

Date Speaker Home Institution Host Type of Chemistry
February 21, 2020 Veronica Hubble University of Notre Dame Gretchen Potts Medicinal Chemistry
         
March 20, 2020 Paul Wagenknecht Furman University John Lee Inorganic Chemistry
         
April 3, 2020 Ron Pongdee Sewanee Jared Pienkos Organic Chemistry

 

Ms. Veronica Hubble (University of Notre Dame)

Using Small Molecule Adjuvants to Combat Antibiotic Resistant Bacteria in Cystic Fibrosis

Abstract:  Cystic fibrosis (CF) is a life-threatening disease inherited by approximately one in 2,500
American children each year. CF is diagnosed by defects in the cystic transmembrane
conductance regulator (CFTR) gene, which causes an over-accumulation of thickened mucus
that coats the lungs and acts as an ideal breeding ground for bacterial infections. The main cause
of fatality in CF patients is directly related to infection with a deadly bacterial pathogen,
Pseudomonas aeruginosa. Antimicrobials are the main treatment focus for CF due to the
patient’s vulnerability to infection. The highly adaptive nature of P. aeruginosa, in addition to
the intrinsic resistance to many antibiotics exhibited by most Gram-negative bacteria, means that
multi-drug resistant (MDR) strains are increasingly prevalent. This results in eradication of
pseudomonal lung infections becoming nearly impossible once the infection becomes chronic.
New methods to treat pseudomonal infections by both lowering inflammation within the
respiratory tract and eradicating the bacteria responsible for this inflammation are greatly needed
to better the quality of life for CF patients. Azithromycin is a macrolide antibiotic currently
prescribed to CF patients as an anti-inflammatory agent due to its well-documented ability to
lower inflammation in patients with known respiratory diseases. However, P. aeruginosa
exhibits intrinsic resistance to macrolide antibiotics, including azithromycin, making this
antibiotic ineffective in eradicating infections caused by this bacterium. Herein, we describe a
novel approach for combatting pseudomonal infections through the use of nonmicrobicidal bis-2-
aminoimidazole (bis-2-AI) adjuvants that suppress azithromycin resistance in a highly resistant
strain of P. aeruginosa. Our lead bis-2-AI exhibits a 1024-fold reduction in the minimum
inhibitory concentration of azithromycin in vitro and increases survival rates in a Galleria
mellonella model of infection, demonstrating the potential dual use of azithromycin not only as
an anti-inflammatory agent, but also as an antibiotic for CF treatment regimens.

 

Dr. Paul Wagenknecht (Furman University)

 

Dr. Ron Pongdee (Sewanee: The University of the South)