Combating Antibiotic Resistance by Exploring Bacterial Envelope Stress Response as the Mechanism for Enhancing Collateral Sensitivity to Antibiotics
DescriptionAntibiotic resistance is a major threat to human health. Our team has recently identified 430 bioinformatically predicted antimicrobial peptides (AMPs) from fish plasma. One of them (BING) shows broad-spectrum antibacterial toxicity through the suppression of CpxR, a master regulator of Envelope Stress Responses (ESR). We showed that BING can suppress the emergence of antibiotic resistance in E. Coli. These data suggest ESR is a novel target for a new generation of drugs that can suppress antibiotic resistance, thus extending the functional span of existing antibiotics. Building on this foundation, we propose to explore the commercial application of BING as an inducer of sensitivity towards antibiotics in Pseudomonas aeruginosa, a clinically important species. P. aeruginosa will be passaged in antibiotic-containing media in the presence of BING. Bacterial growth will be monitored in order to determine the rate of resistance development. We will also test the role of CpxR in BING’s effect on antibiotic resistance by deleting and overexpressing this gene in P. aeruginosa. The outcome of this project will establish BING as a lead compound that can control antibiotic resistance. The results of this project are patentable, and will be used as the basis for an ITF application.
|Effective start/end date||1/09/19 → …|