Designing new antibiotics with a focus on gut health

The discovery of antibiotics massively transformed medicine, but this transformation is now jeopardized by the rapid escalation of antimicrobial resistance (AMR). The spread of AMR is attributed to the use and misuse of antibiotics, creating selective pressures that fuel the growth of resistant bacteria in healthcare and agriculture. A key strategy to overcome AMR is to chemically modify existing drugs to create semi-synthetic analogues that have similar activity but evade resistance. However, these efforts have neglected the impacts of new drugs on the gut microbiome, a crucial community of commensal bacteria that resists pathogenic invasion through colonization resistance. Rather, new antibiotics are typically optimised for potency against pathogens above all else, irrespective of collateral effects on the microbiome. As a result, antibiotics can indiscriminately suppress the beneficial members of the gut microbiome alongside any pathogens. My project aims to address this problem by synthesising a library of new antibiotics and assessing their effects on both pathogens and the human gut microbiome. In doing so, I aim to both develop more microbiome friendly drugs and seek general rules underlying the selectivity of small molecule antibiotics.

UKRI-BBSRC Priority Areas: Combatting antimicrobial resistance, integrative microbiome research