The hitchhiker's guide to the periplasm: Unexpected molecular interactions of polymyxin B1 in E. coli.
Structure
; 29(5): 444-456.e2, 2021 05 06.
Article
in En
| MEDLINE
| ID: mdl-33577754
ABSTRACT
The periplasm of Gram-negative bacteria is a complex, highly crowded molecular environment. Little is known about how antibiotics move across the periplasm and the interactions they experience. Here, atomistic molecular dynamics simulations are used to study the antibiotic polymyxin B1 within models of the periplasm, which are crowded to different extents. We show that PMB1 is likely to be able to "hitchhike" within the periplasm by binding to lipoprotein carriers-a previously unreported passive transport route. The simulations reveal that PMB1 forms both transient and long-lived interactions with proteins, osmolytes, lipids of the outer membrane, and the cell wall, and is rarely uncomplexed when in the periplasm. Furthermore, it can interfere in the conformational dynamics of native proteins. These are important considerations for interpreting its mechanism of action and are likely to also hold for other antibiotics that rely on diffusion to cross the periplasm.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymyxins
/
Escherichia coli Proteins
/
Periplasmic Binding Proteins
/
Bacterial Outer Membrane
/
Anti-Bacterial Agents
Language:
En
Journal:
Structure
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
United kingdom