A Chemical Screen for Chemical Compound Modulators of the Vibrio Cholerae Phosphotransferase System

Undergraduate #27
Discipline: Biological Sciences
Subcategory: Microbiology/Immunology/Virology

Mahtab Waseem - Howard University
Co-Author(s): Emmanuel Ike, Kalah Ozimba, and Terinney Haley, Howard University, Washington, DC

---

Phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) is a multistep chemical process which regulates the intake and use of carbohydrates by bacteria. When bacteria grow through the use of nutrients, such as sugars, they may for a biofilm which in essence is a layer of bacterial cells that grow attached to one another in a film. In addition to controlling the sugar usage of bacteria, the PTS also regulates several cellular functions such as chemotaxis, glycogen metabolism, catabolite repression and the aforementioned biofilm formation. We hypothesize that given the established connection between PTS activity and biofilm formation in several biological species, the identification of small-molecule that can interfere with PTS activity will suggest new tools and approaches for the control of microbial biofilms. In order to do this, we have developed an assay to screen for Vibrio cholerae sugar fermentation. The screen uses sucrose, a sugar which can only be transported by the PTS. This screen was then used to test dozens of compounds which were selected for their physiochemical properties, such as solubility, decreased toxicity, and increased stability. For the screen assay, a V. cholerae O139 strain, MO10, growing in the absence of chemical compounds served as a negative compound. An altered strain, which lacked PTS activity, served as a positive control. Preliminary data suggests that some of the compounds screened exhibit antibacterial activity, while others seem to interfere with the ability of Vibrio to ferment sucrose. This interference may be due to interaction with the PTS. Success of this project will result in the identification and characterization of antimicrobial compounds that inhibit the bacterial PTS system and regulate biofilm formation. This may lead to the development of novel microbial control strategies with applications in engineering, physical, biological, medical, and pharmaceutical sciences.

Funder Acknowledgement(s): This study was supported by a grant from NSF (Research Initiation Award #1505301) awarded to Patrick Ymele-Leki PhD, Assistant Professor of Chemical Engineering, Howard University, Washington, DC 20059.

Faculty Advisor: Patrick Ymele-Leki,