各位老师和同学：
大家好，2024年7月19日（星期五），化学生物学与生物技术学院邀请了张桢润博士到访我院并进行“Chemical biology at the intersection of host-microbe-metabolite tripartite relationship”的讲座，欢迎大家参加！
嘉宾：张桢润
嘉宾单位：University of Chicago
主题：Chemical biology at the intersection of host-microbe-metabolite tripartite relationship
时间：2024年7月19日（星期五）16：00-17：00
地点：F101
邀请人：彭涛
讲座摘要：
Interactions between intestinal microbiota and their host are largely mediated by microbial- and host-derived metabolites. Chemical biology emerges as a powerful tool in dissecting the molecular mechanisms among this tripartite relationship.
Firstly, I’ll present a case study that uses chemical biology to illustrate how butyrate, a key microbial metabolite, provides gut colonization resistance. Using chemical proteomics, we found that HilA, a transcriptional regulator of Salmonella pathogenicity island-1 (SPI-1), was a key target of butyrate. CRISPR–Cas9 gene editing and unnatural amino acid mutagenesis revealed that site-specific modification of HilA impacts its genomic occupancy, expression of SPI-1 genes and attenuates Salmonella enterica serovar Typhimurium virulence. Our results suggest that prominent microbiota-derived metabolites may directly acylate virulence factors to inhibit microbial pathogenesis in vivo.
Secondly, I’ll discuss how chemical biology aids in understanding interactions between lantibiotics and human gut commensals. We demonstrate that Nisin, a lantibiotic commonly added to food products, alters fecal microbiome compositions and bile acid profiles in mice. We show that Lantibiotic Resistance genes (LRG) are prevalent in microbiomes across diverse human cohorts. Bacterial strains encoding LRG have enhanced fitness upon Nisin exposure but reduced fitness without lantibiotic pressure. We further mined novel gut-derived lantibiotics from public dataset and performed Structure–activity relationship (SAR) studies that revealed key residues that impact their antimicrobial properties against human gut pathogens and commensals. Our studies highlight the prevalence, abundance and physiologic significance of an underappreciated subset of antimicrobial resistance genes in human gut bacterial species, underscoring the need for innovative antimicrobial strategies.
嘉宾简介：
Hailed from Shenzhen, I got my B.S. from College of Chemistry and Molecular Engineering from Peking University in 2012, finishing my undergraduate research in Peng R. Chen’s lab. I got my Ph.D. from The Rockefeller University with Howard C. Hang as my advisor. In 2019, I joined Eric G. Pamer’s lab as a postdoctoral scholar in the newly established Duchossois Family Institute at The University of Chicago, a microbiome institute with focus on translational medicine. My research work has long been focusing on the tripartite relationship among microbes, metabolites, and host. My postdoctoral research was funded by Gastro-Intestinal Research Foundation Early Career Grant, and my work had been selected for presentations in Keystone conferences and Cold Spring Harbor Laboratory Microbiome conference.
