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Structural biology of adhesin-like proteins in the bacterial predator bdellovibrio

Principal Supervisor: Dr Andrew Lovering - School of Biosciences

Co-supervisor: Damon Huber

PhD project title: Structural Biology of Adhesin-like Proteins In the Bacterial Predator Bdellovibrio

University of Registration: University of Birmingham

Project outline:

Bdellovibrio bacteriovorus bacteria are natural inhabitants of soil & water and are also found in the oral & faecal flora of animals & man – they are predatory towards other bacteria (including many pathogens, antibiotic-resistant strains) and possess a remarkable lifecycle where they invade the periplasmic space of their prey. Essentially, the larger bacterial prey is eaten from within. An overview of this process is described here.

Bdellovibrio can be taken orally by farmed poultry without health-related side-effects; they reduce the numbers of infectious Salmonella in infected birds (Atterbury et al 2011). This orally-ingested-safety bodes well for the application of Bdellovibrio in the future as a topical agent for mouth, foot & skin infections of animals and as a spray for crop pathogens. These exciting applications are now in the process of being expanded upon (Reardon 2015).

We are using X-ray crystallography and related methods to uncover the mechanisms by which Bdellovibrio proteins manipulate and metabolize prey bacteria (e.g. Lovering et al 2011, Lerner et al 2012, Lambert et al 2015). This project will look at a specific subset of these predatory proteins (those possessing domains predicted to be involved in adhesion) and use information derived from high resolution protein structures to describe prey interaction at the molecular level. This structural biology approach is particularly powerful in the study of this unusual bacterium, as homology to other organisms is weak (predators are uniquely adapted to their unusual lifestyle, wherein a proportion of their genome reflects this extreme specialization). By understanding the association of predator and prey outer surfaces, it may be possible in future to manipulate prey range (specifically which species are amenable to killing by Bdellovibrio).

References:

  1. Atterbury RJ, Hobley L, Till R, Lambert C, Capeness MJ, Lerner TR, Fenton AK, Barrow P, Sockett RE. Effects of orally administered Bdellovibrio bacteriovorus on the well-being and Salmonella colonization of young chicks. Appl Environ Microbiol. 2011 Aug 15;77(16):5794-803
  2. Lambert C, Cadby IT, Till R, Bui NK, Lerner TR, Hughes WS, Lee DJ, Alderwick LJ, Vollmer W, Sockett ER, Lovering AL. Ankyrin-mediated self-protection during cell invasion by the bacterial predator Bdellovibrio bacteriovorus. Nature Commun. 2015 Dec 2;6:8884
  3. Lerner TR, Lovering AL, Bui NK, Uchida K, Aizawa S-I, Vollmer W, Sockett RE. Specialized peptidoglycan hydrolases sculpt the intra-bacterial niche of predatory Bdellovibrio and increase population fitness. PLoS Pathogens. 2012; 8(2):Feb 9 e10025424
  4. Lovering AL, Capeness MJ, Lambert C, Hobley L, Sockett RE. The Structure of an unconventional HD-GYP Protein from Bdellovibrio Reveals the Roles of Conserved Residues in This Class of Cyclic-di-GMP Phosphodiesterases. mBio. 2011 Oct 11;2(5)
  5. Reardon 2015. http://www.nature.com/news/antibiotic-alternatives-rev-up-bacterial-arms-race-1.17621

BBSRC Strategic Research Priority: Food Security

Techniques that will be undertaken during the project:

  • Molecular Biology (chiefly cloning, mutagenesis)
  • Protein expression & purification
  • Protein crystallization Structure Determination
  • X-Ray Crystallography
  • Protein function/analysis
  • Enzyme Assays
  • Biophysical methods (AUC, SAXS, ITC, microscale thermophoresis)
  • Bioinformatics

Contact: Dr Andrew Lovering, University of Birmingham