Amanda Luraschi Eggemann (Muttenz / CH), Anthony Vocat (Muttenz / CH), Gregory Resch (Lausanne / DE), Alexander Sturm (Muttenz / CH)
Background: Due to the spread of antimicrobial resistance and the slow development of new antibiotics, alternatives, such as bacteriophages, are coming into focus. Besides clear evidence of the clinical interest of phage therapy, its implementation requires fast and reliable phage susceptibility testing (PST) to select the right phage(s) to treat the patients.
Methods: As an alternative to complex and time-consuming standard Drop Tests Assays (DTA), we developed a new technology1-4, based on real time measuring of living cell vibrations in response to a phage. These vibrations or nanomotions are recorded with a micromechanical sensor bearing a cantilever and the Phenotech device that is currently in clinical studies for antibiotic susceptibility testing (AST) in bloodstream infections.
Results: We present the first data obtained with the Phenotech device measuring the response of Pseudomonas aeruginosa ATCC-15442 to two different phages. at different concentrations (MOI, Multiplicity Of Infection). Our recordings show the dose-dependent lysis of cells in real-time. In a second step, we moved to several clinical isolates mostly from cystic fibrosis patients and developed a classification model for clear and turbid phenotypes referenced to empirical DTA. In only 6 h, the Phenotech PST was able to discriminate between clear and turbid phenotypes with an accuracy of 89%.
Conclusion: We plan to extend our experiments to a larger set of P. aeruginosa patient isolates and phages and continue training classification models with supervised machine learning based on common features from the nanomotion signal. A nanomotion-based PST could fill the current gap in fast PST, helping clinical implementation of phage therapy.
1 Longo, G. et al. Nat Nanotechnol 2013
2 Kasas, S. et al. Antibiotics 2021
3 Villalba, M. I. et al. Small 2018
4 Vocat, A. et al. Microbes and Infection2023