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Structure & Function of Predatory Bacteria Prey Exit Processes

Primary Supervisor: Dr Andrew LoveringLink opens in a new window, School of Biosciences

Secondary supervisor: Professor Dave GraingerLink opens in a new window

PhD project title: Structure & Function of Predatory Bacteria Prey Exit Processes

University of Registration: University of Birmingham

Project outline: 

    The bacterial predator Bdellovibrio bacteriovorus is a natural killer of other bacteria, and may eventually be used in a therapeutic or bioremediation context. It would thus be beneficial if we understood the molecular basis of its predatory lifestyle, and the “toolkit” encoded to manipulate (and eventually destroy) the prey cell. The staged lifecycle of predation is fascinating – the predator locating and entering the prey cell, metabolizing it from within, and then bursting out to begin the cycle anew.

    Efforts to identify key predation genes have been aided by RNAseq and array studies (1), and a recent transposon-based method to screen for essentiality (2). The Lovering lab specializes in protein structure:function relationships, and the basis of this project will be taking a select grouping of essential, yet cryptic genes whose timing indicates expression at the key point of prey cell rupture. We will use structural information to infer the role played in predation, collaborating with the laboratory of Simona Huwiler (University of Zurich, Switzerland) on in-vivo functionality.

    An overview of our approach can be seen here: https://www.youtube.com/watch?v=FioNZppFlKY, and good examples of discerning predatory function via structure can be taken from two of our recent publications (3, 4). Structure is particularly important because Bdellovibrio is unique and shares limited sequence homology with “traditionally well-characterized” bacteria. For example, our first clues into exit recently resulted in the discovery of a novel lysozyme that recognizes a chemical marker which Bdellovibrio uses to signify prey wall as different to self (5).

    There are many other potential “secrets” to uncover about prey cell exit, including maximizing usage of prey cell macromolecules, proper development of the new progeny cells to prepare for another round of killing, and cryptic functions that only make sense in the light of discovery!

    References:

    1. Caulton SG, Lovering AL. Bacterial invasion and killing by predatory Bdellovibrio primed by predator prey cell recognition and self protection. Curr Opin Microbiol. 2020. https://www.sciencedirect.com/science/article/pii/S1369527420300837?via%3Dihub
    2. Lambert C, Chang CY, Capeness MJ, Sockett RE. The first bite--profiling the predatosome in the bacterial pathogen Bdellovibrio. PLoS One. 2010 Jan 6;5(1):e8599.
    3. Duncan MC, Gillette RK, Maglasang MA, Corn EA, Tai AK, Lazinski DW, Shanks RMQ, Kadouri DE, Camilli A. High-Throughput Analysis of Gene Function in the Bacterial Predator Bdellovibrio bacteriovorus. MBio. 2019 Jun 11;10(3). pii: e01040-19.
    4. Cadby IT, Basford SM, Nottingham R, Meek R, Lowry R, Lambert C, Tridgett M, Till R, Ahmad R, Fung R, Hobley L, Hughes WS, Moynihan PJ, Sockett RE, Lovering AL. Nucleotide signaling pathway convergence in a cAMP-sensing bacterial c-di-GMP phosphodiesterase. EMBO J. 2019 Sep 2;38(17):e100772.
    5. Meek R, Cadby IT, Moynihan, PJ, Lovering AL. Structural Basis for Activation of a Bdellovibrio Diguanylate Cyclase that Licenses Prey Entry. Nature Communications accepted 2019.
    6. Harding CJ, Huwiler SG, Somers H, Lambert C, Ray LJ, Till R, Taylor G, Moynihan PJ, Sockett RE, Lovering AL. A Lysozyme with Altered Substrate Specificity Facilitates Prey Cell Exit by the Periplasmic Predator Bdellovibrio bacteriovorus. Nature Communications accepted Aug 2020

    BBSRC Strategic Research Priority: Understanding the Rules of Life: Structural Biology

    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 LoveringLink opens in a new window, University of Birmingham