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Transport of essential nutrients across the outer membrane of a bacterial pathogen

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Gram-negative bacteria possess a second membrane, the outer membrane (OM), that serves as an additional line of defence against noxious agents, including antibiotics. However, this comes at a price, as the OM also serves as a barrier to the uptake of some essential nutrients. Smaller molecules are able to pass through OM porins (pore-forming proteins) in an energy-independent fashion, but larger molecules (certain sugars, vitamins and metal chelates) have to be transported in an energy dependent process. This creates a problem as ATP is not available at the OM. Therefore, Gram-negative bacteria have evolved a mechanism for transducing energy to the OM to allow for active transport of these molecules.

This mechanism involves gated OM receptors known as TonB-dependent transporters (TBDTs). These are β-barrel proteins with an N-terminal plug domain that blocks the channel. When the ligand docks at the surface of the TBDT, the plug moves, thereby allowing access of the ligand to the periplasmic space. The energy for movement of the plug domain is provided by a protein complex known as the TonB system. The TonB system consists of three proteins, TonB itself, ExbB and ExbD, that are anchored to the cytoplasmic membrane. TonB has a long unstructured central region that extends across the periplasmic space and terminates in a folded C-terminal domain that contacts the N-terminal region of the TBDT. It is this interaction between TonB and the TBDT that allows for transduction of the proton motive force generated at the cytoplasmic membrane to the movement of the TBDT plug domain.

Some bacteria have a single type of TonB system that is able to interact with the different TBDTs present in the OM. However, other species contain two, three, or more distinct TonB systems. As an example, Burkholderia cenocepacia, an opportunistic pathogen, encodes three different TonB systems, the TonB1, TonB2 and TonB3 systems. The aim of this project is to elucidate the specific role of each of these systems in B. cenocepacia, i.e. to identify the particular nutrients and their TBDTs that depend on each TonB system. The project will involve a variety of molecular biological, molecular genetic and microbiological techniques.

Funding Notes

Funding:
Open to Home/EU and Overseas students that have secured funding for their studies.

Entry Requirements:
Candidates must have a first or upper second class honors degree or equivalent.

Enquiries:
Interested candidates should in the first instance contact Dr Mark Thomas ()

References

How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply


Please clearly state the prospective main supervisor in the respective box and select 'Infection Immunity & Cardiovascular Disease' as the department.

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