Thesis title: Characterisation of novel bacterial filament systems and their potential as antibiotic targets.
Supervisor: Robert ROBINSON
Bacterial actin-like filament systems (such as ParM and MreB) are needed to carry out essential functions such as cell shape maintenance and plasmid segregation. The aim of the studying bacterial filaments is to understand their biological roles and to assess their potential as novel antibacterial drug targets. First, novel proteins Cb40 ParM and Cb20 ParM were found to assemble into distinct organisations with different sets of structural properties, suggesting that they may have dissimilar mechanisms for DNA segregation. Next, novel MreB-like protein TmMblwas found to be a potential modulator of TmMreB activity in the bacteria T. Maritima and it is likely to assist TmMreB in its cellular functions. Lastly, MreB inhibitors A22 and Mp265 were characterised, they induce MreB depolymerisation by causing conformational changes into its monomeric state. In conclusion, bacterial actin-like proteins (Alp) are great potential targets for a new class of antibiotic, but more work is needed to obtain better Alp perturbing compounds.
(A) TmMreB colocalised with TmMbl in vitro and formed bundles.
(B) MreB inhibitor Mp265 depolymerised TmMreB and TmMbl bundles.
List of publications:
Novel actin filaments from Bacillus thuringiensis form nanotubules for plasmid DNA segregation.
Microtubule-like properties of the bacterial actin homolog ParM-R1.
Popp D, Narita A, Lee LJ, Larsson M, Robinson RC.
J Biol Chem. 2012 Oct 26;287(44):37078-88. doi: 10.1074/jbc.M111.319491. Epub 2012 Aug 20.
Novel actin-like filament structure from Clostridium tetani.
Popp D, Narita A, Lee LJ, Ghoshdastider U, Xue B, Srinivasan R, Balasubramanian MK, Tanaka T, Robinson RC.
J Biol Chem. 2012 Jun 15;287(25):21121-9. doi: 10.1074/jbc.M112.341016. Epub 2012 Apr 18.
Jiang SM, Narita A, Popp D, Ghoshdastider U, Lee LJ, Srinivasan R,. Balasubramanian M, Oda T, Koh FJ, Larsson M, and Robinson RC.
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