Event Title

Determining the Mechanism of Action of the Antibiotic Argyrin B

Co-Author(s)

Riley Roberts, Jessica Mantchev, Justin Walter, Tanner Thuet, Catie Shelton, Amanda Weis

Research Mentor(s)

Clint Spiegel

Description

Elongation factor G (EF-G) is a key bacterial translation factor and GTPase that is highly conserved in bacteria, with homologs in many other organisms. The peptide argyrin B, derived from myxobacteria and actinomycetes targets EF-G specifically. Argyrin B has shown antibiotic activity against the bacteria Pseudomonas aeruginosa and membrane compromised strains of other gram negative bacteria. In order to elucidate the mechanism of action for argyrin B we performed in vitro experiments with the E. coli 70s bacterial ribosomes and different EF-G variants. We initially observed the results of argyrin B on EF-G to 70S binding and the GTPase activity that this binding facilitates. We also examined the binding affinity for substrate analogues. This work then investigated the effects on the two key functions of EF-G, translocation and ribosome recycling. We ascertained from our experimentation that argyrin B increases binding to the ribosome, while having only a marginal effect on GTPase activity and substrate binding. Furthermore argyrin B did not present a change in ribosomal translocation but the drug does appear to inhibit ribosome dissociation, a key step in ribosome recycling. These experiments will narrow the possibilities of the mechanism of argyrin B and work to further the understanding of a unique antibiotic.

Document Type

Event

Start Date

15-5-2019 9:00 AM

End Date

15-5-2019 5:00 PM

Location

Carver Gym (Bellingham, Wash.)

Department

Chemistry

Genre/Form

student projects, posters

Type

Image

Rights

Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this document for commercial purposes, or for financial gain, shall not be allowed without the author’s written permission.

Language

English

Format

application/pdf

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May 15th, 9:00 AM May 15th, 5:00 PM

Determining the Mechanism of Action of the Antibiotic Argyrin B

Carver Gym (Bellingham, Wash.)

Elongation factor G (EF-G) is a key bacterial translation factor and GTPase that is highly conserved in bacteria, with homologs in many other organisms. The peptide argyrin B, derived from myxobacteria and actinomycetes targets EF-G specifically. Argyrin B has shown antibiotic activity against the bacteria Pseudomonas aeruginosa and membrane compromised strains of other gram negative bacteria. In order to elucidate the mechanism of action for argyrin B we performed in vitro experiments with the E. coli 70s bacterial ribosomes and different EF-G variants. We initially observed the results of argyrin B on EF-G to 70S binding and the GTPase activity that this binding facilitates. We also examined the binding affinity for substrate analogues. This work then investigated the effects on the two key functions of EF-G, translocation and ribosome recycling. We ascertained from our experimentation that argyrin B increases binding to the ribosome, while having only a marginal effect on GTPase activity and substrate binding. Furthermore argyrin B did not present a change in ribosomal translocation but the drug does appear to inhibit ribosome dissociation, a key step in ribosome recycling. These experiments will narrow the possibilities of the mechanism of argyrin B and work to further the understanding of a unique antibiotic.