Computational Analysis of the Cystic Fibrosis Lung Microbiome and Development of a Non-Toxic Quorum Quenching Cocktail Therapy To Inhibit Multispecies Biofilm Proliferation
ISEF · 2022 Microbiology First Award
Overview
Bacterial biofilms account for 80% of all chronic microbial infections. ESKAPE pathogens form dense, multispecies biofilms that are resistant to most antibiotics. In this project, a combination treatment of FDA-approved concentrations of quorum quenching agents was devised to target three major interspecies biofilm-pathways: Chlorogenic Acid (CA) inhibiting Pseudomonas fluorescens-Staphylococcus epidermidis HQNO production by targeting Pqs Quorum Sensing (QS), carvacrol inhibiting P. fluorescens-Burkholderia pyrrocinia N-acyl-homoserine-lactone production by targeting Las QS, and 6-gingerol inhibiting P. fluorescens-Candida albicans phenazine production by targeting Rhl QS. Computational analysis of the cystic fibrosis lung microbiome using QIIME2 and PICRUSt2 confirmed the prevalence of these biofilm pathways. Docking analysis supported the binding affinities of each treatment with targeted enzymes (LasR/LasI/PqsR). Dual combinations of microbes were treated with 0.75% carvacrol, 30ug/ml CA, or 32ug/ml 6-gingerol, and the multispecies group was treated with all agents. Of the dual-species groups, CA had a 70% efficacy in inhibiting P. fluorescens-S. epidermidis biofilm, carvacrol a 60% efficacy on P. fluorescens-B. pyrrocinia biofilm, and 6-gingerol a 45% efficacy on P. fluorescens-C. albicans biofilm. The combination treatment demonstrated an 80% efficacy in inhibiting P. fluorescens-S. epidermidis-B. pyrrocinia-C. albicans biofilm. Statistical significance was confirmed using ANOVA and T-test. Treatment safety was supported by a cytotoxicity assay on A549 human alveolar epithelial cells. These findings support the delivery of the cocktail therapy as an adjuvant to antibiotics in-vivo, thus reducing morbidity and mortality from chronic biofilm-related infections.
Awards (3)
- First Award of $5,000 $5,000
- Air Force Research Laboratory on behalf of the United States Air Force: Glass trophy and USAF medal for each recipient
- Air Force Research Laboratory on behalf of the United States Air Force: First Award of $750 in each Regeneron ISEF Category $750
Competition history
- ISEF 2022
Resources
Related projects
ISEF · 2021
Generating a Non-toxic, Multi-pathway Targeted Cocktail Treatment Composed of N- Acetylcysteine, Carvacrol, and DNase to Inhibit Pseudomonas Biofilm Proliferation in vitro
ISEF · 2014
Novel Treatment of Chronic Bacterial Infection: Investigation and Multi-Compound Inhibition of Acyl-homoserine Lactone-Based Quorum Sensing in Pseudomonas aeruginosa and Its Role in Biofilm Development in vitro
ISEF · 2026
Design of a Multi-Mechanistic Triple Therapy to Overcome Biofilm-Associated Resistance in Pseudomonas aeruginosa
ISEF · 2019
Viruses to the Rescue?: Using Microtiter Assays and an In-Lab Developed Simulated Anatomic Lung Model to Determine the Effectiveness of Bacteriophage Therapy as a Preventative Measure against Poly-Microbial Biofilms in Cystic Fibrosis Patients
Closest projects by meaning, across every fair and year in the corpus.
Source: Regeneron International Science and Engineering Fair