Discovery and development of small-molecule antibiotics against C. difficile

Antibiotics are a critical component of modern medicine, allowing the treatment of infection and minimising risk during medical procedures. The rising tide of antimicrobial resistance threatens the utility of our frontline antibiotics and drives the societal demand for novel anti-infective classes. However, developing new drugs to the clinic is tough due to both scientific and economic challenges.

To place further constraints, broad spectrum antibiotics can cause collateral damage to the friendly bacteria of our microbiome, which play important roles in our physiology including protection from the outgrowth of pathogens.

Clostridioides difficile (commonly referred to as C. diff) can cause severe diarrheal infections that can be difficult to treat. The use of broad-spectrum antibiotics is a risk factor for C. diff infection due to the loss of key commensal bacteria that provide colonisation resistance against C. diff spore germination. Further treatment to treat the infection can result in recurrence cycles of infection.

My PhD project aims to identify and develop small molecules with narrow-spectrum activity against C. difficile whilst minimising harm to beneficial commensal bacterial species. Synthetic organic chemistry is the driving force to generate compound libraries, which are screened in collaboration with microbiologists from both Uppsala University and abroad.