C2D2 research 1a - Assessment of the activity of novel antimicrobial therapies against bacterial biofilms: establishing a resource to support non-microbiologists

Project: Other internal award

Project participant(s)

Department / unit(s)

Layman's description

Biofilm growth of bacteria, a mode of growth particularly associated with chronic infections, can confer drug resistant behaviour, complicating treatment of infections. The project brings together microbiology expertise (Van der Woude, CII) to test effectiveness of novel antimicrobial therapies under development, specifically: modifying drugs to circumvent resistance (Duhme-Klair and Routledge, Chemistry), identifying bacterial targets for biofilm inhibiting agents (Potts, Biology), and biomedical plasmas (Plasma Institute). An additional aim is to support the establishment of a University “biofilm interest” network through which resources and strategies can be shared, and encourage the development of complementary strategies.

Key findings

FINDINGS/RESULTS
The outputs are summarized according to the three scientific areas supported:

1. Work that was carried out between the MvdW and ADK/AR groups introduced expertise in Pseudomonas aeruginosa (P.a.), a major pathogen especially in cystic fibrosis, microbiology into CII. The work identified a suitable assay from the literature, and developed and applied this to P.a. for determining biofilm penetration of novel "trojan" horse antimicrobials. Results showed that chemical modifications have unpredicted effects on biofilm penetration. This will inform future compound design. Data will form part of a joint manuscript on these novel compounds (Milner et al, in preparation), with MvdW and MH as co-authors and C2D2 funding acknowledged. The assay, which is now well-established, can be applied to new compounds in the future.

2. The Potts group is studying the formation of staphylococcal biofilms from a structural perspective. It is essential that hypotheses based on the protein structures can be tested in-house in biofilm assays; c2d2 funding has provided this capability. Fundamental differences were observed between strains reported previously to form protein and carbohydrate-mediated biofilms, respectively. Only the strain that forms a protein-mediated biofilm aggregated in solution. This aggregation appears to be zinc-dependent. Other data support and extend observations on the two types of biofilms, and indicate that it is likely that the protein and carbohydrate mediated mechanisms of cell-cell interaction should be considered as fundamentally different in terms of both mechanism and in vivo function. This is an important consideration for further studies on developing therapeutic strategies for Staphylococcal infections.
In addition to these results, a postdoctoral researcher from the Potts lab was trained in the vdW lab so that further assays can be performed as the understanding of the structural biology is advanced.
The work supported and extended a project funded by the British Heart Foundation. Further applications are planned Three manuscripts related to staphylococcal biofilm formation are currently in preparation.

3. Adaptations to the plasma application setup in the CII made applications to biological samples much more amenable. This, along with initial data (supported by WT funded PhD student), helped develop ideas that became part of a funded N8 project on the biological activity of plasma. MH’s C2D2 experience allowed that work to proceed smoothly with new assays trialed. Future work will use the equipment, protocols and build upon gained expertise.
Having a setup that allows plasma application in the CII has already facilitated interactions with other Biologists to assess possible novel applications (Sweeney group; also part of a C2D2 application).

4. The goal of sharing knowledge and insights centred around bacterial infections was achieved. Benefiting from regular discussions and a final meeting, all parties gained appreciation of the potential and complexities of each other’s fields of expertise. New approaches were trialed and established, robust protocols for these were drawn up and staff (Mike Hodgkinson) generated useful data.


COLLABORATIONS
A collaboration between the Potts and van der Woude labs was established. Collaboration between the Plasma Institute and CII strengthened.


STAFF
Dr Gemma Harris was trained in biofilm assays relevant to the S. epidermididis work.
Mike Hodgkinson (C2D2 supported) gained additional expertise in microbiology and advanced imaging techniques.
MvdW gained knowledge and insight into P.a. and S. epidermididis biofilms.
CIDCATS PhD student Angela Privat Maldonado Oct 2012-

COMMERCIALISATION/TRANSLATION
none

APPLICATIONS SUBMITTED
Biomedical plasma therapy for bacterial infections: reasonable risks for significant rewards
Van Der Woude, M., Brockhurst, M. & O'Connell, D.
R15722, British Society for Antimicrobial Chemotherapy
£49,644
1/06/14 → 31/05/15
Also see
Summary for information on manuscripts in preparation and relationship to funded applications

ARTICLES SUBMITTED
None, but see Summary for information on manuscripts in preparation and relationship to funded applications
StatusFinished
Effective start/end date1/03/1230/09/12

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