Decoding the structural logic of drug-resistant biofilms

Title: Decoding the structural logic of drug-resistant biofilms

Speaker: A/Prof Debnath Ghosal, University of Melbourne

Abstract: Biofilms are highly organized microbial communities that exhibit remarkable resistance to antimicrobial treatments and host immune clearance. Despite their clinical and environmental importance, the molecular and structural principles governing how diverse bacterial species assemble into stable, three-dimensional architectures remain poorly understood. In this seminar, I will present our recent work using high-resolution structural biology approaches to investigate the architecture and organization of complex microbial biofilms. By integrating correlative light and electron microscopy (CLEM), focused ion beam (FIB) milling, and electron cryotomography (cryo-ET), we resolve the ultrastructural organization of biofilms in a near-native hydrated state at nanometre resolution. These approaches reveal how bacteria establish spatially defined communities through specialized extracellular structures, including filamentous and fibrillar adhesins that mediate robust cell–cell and cell–matrix interactions. We further dissect the structural details of these extracellular components, providing mechanistic insight into how they bridge cells, organize multicellular assemblies, and contribute to the emergence of drug-resistant biofilms. Our findings highlight that biofilm formation is not a passive aggregation process, but a highly coordinated, structurally encoded assembly driven by defined molecular interactions. Understanding these architectural principles opens new avenues for targeting biofilm integrity and disrupting pathogenic communities.

Bio: Debnath Ghosal is an Associate Professor in the Department of Biochemistry & Pharmacology, University of Melbourne. Debnath received his PhD degree in structural biology from the MRC Laboratory of Molecular Biology, University of Cambridge and postdoctoral training from Caltech. Debnath established his own laboratory at the University of Melbourne in 2020. His group is using state-of-the-art in situ structural biology techniques to investigate host-pathogen interactions, particularly how bacterial and viral pathogens utilize complex molecular machines to cause pathogenesis.