Designing new antibiotics with a focus on gut health

抗生素的发现极大地改变了医学，但这种转变现在受到抗菌素耐药性（AMR）迅速升级的威胁。AMR的传播归因于抗生素的使用和滥用，产生了选择性压力，助长了医疗保健和农业中耐药细菌的生长。克服AMR的一个关键策略是对现有药物进行化学修饰，以产生具有相似活性但避免耐药性的半合成类似物。然而，这些努力忽视了新药对肠道微生物组的影响，肠道微生物组是一个重要的肠道细菌群落，通过定植抗性抵抗病原体入侵。相反，新抗生素通常针对病原体的效力进行优化，而不管对微生物组的附带影响如何。因此，抗生素可以不加区别地抑制肠道微生物组的有益成员以及任何病原体。我的项目旨在通过合成一个新抗生素库并评估它们对病原体和人类肠道微生物组的影响来解决这个问题。在这样做的过程中，我的目标是开发更多的微生物组友好型药物，并寻求小分子抗生素选择性的一般规则。UKRI-BBSRC优先领域：对抗抗生素耐药性，综合微生物组研究

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