University of Sheffield

Phage engineering to generate tailored therapeutics against resistant enterococci

Characterise the receptor binding proteins of phages targeting enterococci from isolated virulent phages of Enterococcus faecalis and Enterococcus faecium. Investigate how phage receptor proteins recognise the EPA(Enterococcal Polysaccharide Antigen). Using both bacterial mutants and phage-resistant strains, and in vitro interaction assays with recombinant receptor binding proteins and purified cell wall fragments to elucidate the molecular mechanism underpinning surface recognition by phages.

Engineer recombinant virulent phages with altered host range. Recombinant phages encoding distinct or combined receptor binding proteins will be assembled in vitro and “rebooted” using Golden Gate assembly to modify or expand their host range using error-prone PCR, and explore the possibility of generating phages with extended host range.

Explore the therapeutic potential of recombinant phages and the antimicrobial activity of phages against planktonic cultures and biofilms to be tested. Also, investigate how phages eradicate infections in the context of host-pathogen interaction using in vitro models and the zebrafish experimental model of infection.

Apply here https://www.sheffield.ac.uk/biosciences/postgraduate/phd

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