Abstract:

The gut microbiota has a profound impact on host biology. My lab employs chemical biology approaches to uncover the molecular underpinnings of gut microbiota–host crosstalk. In this talk, I will share our recent findings on gut microbiota–derived peptidoglycan fragments (PGNs) as key signaling molecules mediating bacterial–host communication and bacterial–fungal interactions. Using a robust LC-HRMS/MS analytical platform, we profiled natural PGN subtypes in the host gut. Our studies revealed that the disaccharide GlcNAc-MurNAc (GM), a prominent PGN motif, functions as a novel TLR4 agonist and protects against colonic inflammation in the colitis mouse model. These results provide valuable insights into the role of natural PGNs in maintaining host intestinal homeostasis.

Additionally, gut microbiota–derived PGNs are potent inducers of invasive hyphal growth in Candida albicans, a major human fungal pathogen. We recently identified the long-sought PGN transporter in C. albicans and demonstrated that Ssy1 acts as an extracellular sensor for PGNs, playing a crucial role in mediating invasive growth. Deletion of Ssy1 renders C. albicans unresponsive to beta-lactam-induced PGN storms in the mouse gut, significantly reducing its virulence and systemic dissemination. Our findings position Ssy1 as a potential anti-virulence target for preventing PGN-induced invasive growth of C. albicans in hosts.

Bio:

Yuan Qiao is currently the Nanyang Assistant Professor at the School of Chemistry, Chemical Engineering and Biotechnology (CCEB) in Nanyang Technological University (NTU), Singapore. Her lab uses chemical biology tools to study the chemical basis of gut microbiota-host crosstalk, particularly focusing on bacterial peptidoglycan fragments (PGNs) in hosts. Yuan was a recipient of the Singapore A*STAR National Science Scholarship (2007-2016) and the Singapore National Research Foundation Fellowship Class of 2020, and EMBO Global Investigator 2025.