Visualizing Teixobactin Supramolecular Assemblies and Cell Wall Damage in B. Subtilis Using CryoEM.
Paul Joshua Hurst1, Michael A Morris1, Annissa A Graham1
1Department of Chemistry, University of California-Irvine, Irvine, California 92697-2025, United States.
ACS Omega
|October 25, 2021
Summary
The antibiotic teixobactin forms sheet-like assemblies that target bacterial cell walls. Lower concentrations show transient or sparse aggregation on the cell surface, indicating its mechanism of action.
Area of Science:
- Microbiology
- Biochemistry
- Structural Biology
Background:
- Teixobactin is a potent antibiotic targeting bacterial cell walls.
- Its active form was previously hypothesized to be a nano-/micron-sized supramolecular assembly.
Purpose of the Study:
- To elucidate the structural assembly of teixobactin and its interaction with bacterial cell walls.
- To characterize the physical state of teixobactin at different concentrations.
Main Methods:
- Cryogenic transmission electron microscopy (cryo-TEM) was employed.
- Teixobactin assemblies were analyzed at concentrations of 1 mg/mL and 4 μg/mL.
Main Results:
- At 1 mg/mL, teixobactin forms distinct sheet-like assemblies.
- These assemblies were observed to selectively act upon the bacterial cell wall.
- At the active concentration of 4 μg/mL, teixobactin exhibited transient or sparse aggregation at the cell surface.
Conclusions:
- Teixobactin's mechanism involves sheet-like supramolecular assemblies targeting the cell wall.
- The concentration-dependent aggregation behavior influences its activity and interaction with bacteria.
