College
Buchtel College of Arts and Sciences (BCAS)
Date of Last Revision
2023-05-03 16:44:27
Major
Biology
Honors Course
3100 499-003
Number of Credits
3
Degree Name
Bachelor of Science
Date of Expected Graduation
Spring 2020
Abstract
Since their discovery over a century ago, antibiotics have been a staple of combating infectious diseases. However, bacteria develop resistance to antibiotics through a variety of mechanisms. Efforts to identify new antibiotics often fail by discovering already-known antibiotics, or failing to synthesize new antibiotics that are safe for clinical use. The aim of this research was to dereplicate bacteria- to screen for antibiotic production in- normally isolated in cave ecosystems. Using two new technologies, the Antibiotic Resistance Platform (ARP) and a data acquisition and bioinformatics technique (IDBac), my dereplicating method allowed high throughput of bacterial screening for antibiotics. In this work, 252 bacterial isolates from Lechuguilla Cave, NM, were screened using IDBac spectra data to cluster into 21 unique groups. These groups were then dereplicated for novel antibiotic production using the ARP using an Escherichia coli ΔΔbamBtolC mutant with limited efflux that was previously engineered to express resistance genes to several classes of antibiotics. Growth of the E.coli resistant strains indicated which antibiotics were being produced, while those with no growth had the potential to produce an unknown antibiotic or adjuvant. Using this approach, a library of over 600 bacterial strains was dereplicated and 18 lead strains were identified. This novel dereplication method therefore demonstrates the ability to rapidly screen cave isolates, allowing large libraries of isolates to be rapidly screened in the future for novel antibiotics.
Research Sponsor
Dr. Hazel Barton
First Reader
Dr. Robert Joel Duff
Second Reader
Dr. Richard Londraville
Honors Faculty Advisor
Dr. Brian Bagatto
Recommended Citation
Archey, Alexander, "High-throughput two-stage dereplication of cave bacteria to discover novel antibiotic compounds" (2020). Williams Honors College, Honors Research Projects. 1200.
https://ideaexchange.uakron.edu/honors_research_projects/1200