Rebbekah Menday

Structures and Mechanisms in killing C. difficile by Bacteriophages

About me

I completed my undergraduate degree in Biochemistry and Microbiology at the University of Sheffield in 2021. I specialised in structural biology during my undergraduate studies. My third year project focused on using x-ray crystallography to determine the structure of SAG proteins from an apicomplexan parasite. In addition, I completed a summer project determining the structure of the MLA complex within pseudomonas using cryoEM. I have always found phages fascinating. Human beings have tirelessly attempted and sometimes achieved treating diseases caused by bacteria. Nature, however, supersedes our attempts as the existence of these phages co-evolve with their bacterial host in a constant battle for survival. Therefore, phages are a prime candidate for antimicrobial treatments, especially when targeting antibiotic resistance bacteria.

My research

Clostridioides difficile is the leading cause of antibiotic-associated diarrhoea. Antibiotic exposure enables C. difficile to thrive by disrupting the protective gut microbiota and current treatments exacerbate this dysbiosis resulting in frequent recurrence. Therefore, new species-specific treatments are urgently needed. Bacteriophage-based therapies are a promising strategy for treating C. difficile, but exploitation will require a deeper understanding of the mode of action of these obligate intracellular parasites. For example, it is not known how C. difficile phages recognise their cell surface receptors, the location of binding and what changes occur while undergoing binding and cell penetration. Therefore, understanding the binding mechanics of bacteriophages to the C. difficile cell-surface and how the subsequent cell envelope penetration occurs is critical to aid the design of new therapeutics. Consequently, our work focuses on understanding the 3D structural molecular detail of phage binding and penetration of the cell envelope. To achieve this, we are determining the structure of selected C. difficile phage(s) using CryoEM and single particle analysis and combining this with electron cryotomography of phages bound to bacterial cells. By combining these structural data, we aim to develop a detailed molecular understanding of the infection process.



Twitter: @BeckyMenday