Unlocking the Potential of Bacterial ParE Toxins: Developing a Blueprint for Co-Opting Molecular Time Bombs That Impact Bacterial Cell Survival
Abstract
This project aims to Unlock[ing] the potential of bacterial ParE toxins: developing a blueprint for co-opting molecular time bombs that impact bacterial cell survival. The central problem addressed by the aims is of treating bacterial infections with an outcome of making existing antibiotics work better, and in understanding a fundamental bacterial mechanism that may help bacteria become resistant. When successful, this will provide an innovative new way to control bacterial growth, including antibacterial resistant strains. During the funding period we established a potent toxicity of ParE toxins to their native bacterial hosts. Some variation in the absolute toxicity was noted, and appears to reside with the toxin itself rather than the host bacteria. One toxin, as previously noted, is attenuated and does not mediate decreased growth. We found that the extent of toxicity correlates with an increase in the frequency of mutations except for in P. aeruginosa, which appears to have potent repair pathways. However, the increased mutation frequency does not correlate to loss of sensitivity to antibiotics. Surprisingly we note a collateral sensitivity such that ParE expression increases the impact of some antibacterial classes, including anti-gyrase antibiotics. Technical complication limited progress on Aim 2, which was designed to demonstrate antitoxin removal and thus liberation of ParE toxins within cells. Continued optimization of novel detection methods is being explored beyond the current proposal.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2023
- Accession Number
- AD1219300
Entities
People
- Christina R Bourne
Organizations
- University of Oklahoma