SUPPLY: SUperfast Photonic detection of Phage LYsis

Multidrug bacteria resistance is spreading fast and, in the absence of new approaches, 10 million victims per year are envisioned by 2050. Phage therapy, i.e. the therapeutic use of bacterial viruses called bacterio(phages), is currently strongly investigated for its potential to stop bacteria whenever antibiotics are no longer effective. However, a personalized approach is largely awaited mainly because of the narrow specificity of phages and stability issues with complex pre-assembled phage cocktails. Such a personalized strategy requires a deep-understanding of the phage-bacteria interaction as well as the capacity to quickly select the right phage(s) for the right patient. In this context, SUPPLY aims at developing a disruptive interdisciplinary methodology based on cutting-edge technologies from the fields of biophotonic microsystems and microbiology for the deep study of phage-bacteria interactions in the framework of modern phage therapy. A first goal of SUPPLY is to develop optical microresonators for the nondestructive trapping of bacteria and phages for fine characterization of the interaction of phages with a single bacterium. Such experiments yield the great potential of superfast photonic detection of bacterial lysis by phages, bringing new insights into fundamentals of phage-bacteria interactions and their photonic signatures. A second goal is to provide breakthrough approaches for quick phage bank screening to select the most active phages, which is a crucial step for successful treatments. In a third goal, SUPPLY aims to initiate single-phage biophysics, i.e phage-bacteria interaction studies at the single-phage level. By investigating phage-bacteria interaction from the single-bacterium and the single-phage perspectives, SUPPLY will develop new biophotonic systems for fast phage susceptibility testing, paving the road to the application of a new technology able to reduce the time needed to select the right phage(s) for the patients. Therefore, SUPPLY will contribute to support phage therapy implementation by providing microbiologists and physicians with a new tool to therapeutic success. SUPPLY gathers a multidisciplinary consortium of highly complementary expert teams in the fields of phage biology and therapy (Resch-CHUV), photonics (Houdré-EPFL), optical instrumentation (Hadji-CEA) and micro-nanofabrication (Zelsmann-CNRS). Resch-CHUV will select phage and bacterial strains of two highly relevant ESKAPE bacterial species, and provide physicists (Houdré-EPFL, Hadji-CEA) with biological models for their development of optical devices, i.e. 1D nanobeam microcavity for optical trapping of micronic objects (bacteria) and hollow 2D photonic crystals cavity for the trapping of submicron objects (phages). In a second step, micro-nanofabrication capabilities will be implemented to enable large scale and faster analysis and testing in real-life conditions. For the very first time, physicists, biophysicists, and microbiologists will join efforts to study the interaction of phages with their bacterial preys, targeting the same goal: increasing knowledge about phage-bacteria interactions to improve personalized phage therapy protocols and help this promising antibacterial therapy to become a reality for patients.