Karolina Pyrzanowska

Biochemical and structural basis of bacteriophage tail-associated hydrolases of Diabetic Foot Ulcer AMR pathogens

About me

I am interested in all aspects of phage biology such as their evolutionary mechanisms, molecular biology, and clinical applications. My undergraduate project at the University of the West of England, Bristol, supervised by Dr Dann Turner, focused on characterising a giant Acinetobacter bacteriophage TRS5, which provided an invaluable basis for my future research endeavours. During my undergraduate studies, I completed a year-long lab placement with Prof Gail Christie at Virginia Commonwealth University in the USA, in which I helped develop an in vivo cleavage assay for a phage related ribosomal cysteine protease by exploiting the alpha-complementation of beta galactosidase system. This protease proved critical to Staphylococcus aureus survival and as such shows great promise as a target for novel antibiotics.

These experiences paved the way for my MRes at the University of Liverpool, where under the supervision of Dr James Hall, I investigated mobile genetic elements, their interactions and coevolution between each other and the bacteria that harbour them. My project focused on the interactions between phages and conjugative plasmids in Pseudomonas fluorescens SBW25. Having had these experiences and built up a comprehensive understanding and affinity for scientific research and my specialism I decided to embark on a PhD that brought together all the elements of my interests.

My project

Bacteriophage viruses are able to bind, infect and then lyse target bacterial cells. This process involves several stages, beginning with adherence to and penetration of bacterial cell envelopes, which involves Virion Associated Peptidoglycan Hydrolases (VAPGH) and extracellular depolymerases targeting the capsule, peptidoglycan or lipopolysaccharides. Once the phage has replicated within its host and reached a critical concentration the cell is lysed via action of holins and endolysins. This group of viruses has great potential as novel antimicrobials to target antimicrobial resistant (AMR) pathogens, and their antimicrobial enzyme complement is also of great interest. Through a combination of lab-based research and bioinformatics, my project aims to use live phage and their enzymes in the treatment of chronic topical Diabetic Foot Ulcers (DFU) caused by a variety of pathogens such as coagulase negative Staphylococci, Corynebacterium striatum and a range of highly resistant of antibiotics anaerobes. The PhD is supervised by Prof Graham Stafford (School of Clinical Dentistry) and Dr John Rafferty (Department of Molecular Biology and Biotechnology).


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