Structure and operation of bacterial tripartite pumps
Philip Hinchliffe1, Martyn F Symmons, Colin Hughes
1Department of Pathology, Cambridge University, Cambridge CB2 1QP, United Kingdom; email: ph298@cam.ac.uk , mfs@mole.bio.cam.ac.uk , ch@mole.bio.cam.ac.uk , vk103@cam.ac.uk.
Annual Review of Microbiology
|July 2, 2013
Summary
Bacterial tripartite pumps export toxins and antibiotics, aiding survival against multidrug-resistant pathogens. Atomic structures reveal pump assembly and operation, offering insights into potential inhibition strategies.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Bacteria utilize tripartite membrane pumps for efflux of toxins, antibiotics, and other molecules.
- These pumps are crucial for bacterial survival, especially in infections involving multidrug-resistant pathogens.
- Tripartite pumps span the bacterial cell envelope, comprising an inner membrane transporter, a periplasmic adaptor, and an outer membrane TolC duct.
Purpose of the Study:
- To review atomic structures of tripartite pump components.
- To elucidate high-resolution views of tripartite pump assembly and operation.
- To discuss potential strategies for inhibiting tripartite pump function.
Main Methods:
- Review of existing atomic structure data for tripartite pump components.
- Analysis of structural information to understand pump assembly and mechanism.
- Discussion of implications for drug development and inhibition.
Main Results:
- Detailed atomic structures of the inner membrane transporter, periplasmic adaptor, and TolC duct are available.
- Structural insights provide a high-resolution understanding of how these components assemble and function together.
- The review highlights conserved mechanisms across different bacterial species.
Conclusions:
- Atomic structures of tripartite pump components are key to understanding their function.
- High-resolution structural data facilitates the study of pump assembly, operation, and inhibition.
- This knowledge can inform the development of novel strategies to combat multidrug resistance.
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