Investigation of links between bacterial omics and clinical phenotypes

Led by F. Vandenesch in collaboration with J. Lemoine (UMR CNRS 5280, Lyon) and J.P. Rasigade (CIRI team Vanhems) with contributions of K. Moreau (PU) and C. Bouchiat (MCU-PH), and assistance of S. Bastien (engineer).

The identification of Pathovars in S. aureus is still controversial and there are only few described associations between genotypic traits and diseases. Our objective is to test whether differential expression levels of S. aureus virulence factors contribute to variations in severity and outcome of S. aureus-related infections. To this end a high throughput proteomic method initially developed with bioMérieux and recently expanded to a much larger panel of virulence factors by J. Lemoine (Institut des Sciences Analytiques - UMR CNRS 5280, Lyon) with whom we collaborate, will be applied on several strain collections from patient cohorts of community-acquired pneumonia, bacteremia with or without infective endocarditis, and acute and chronic BJI patients. These collections include detailed clinical, biological and therapeutic data for each patient, allowing to model the relations of virulence expression with clinical parameters. Preliminary analysis indicates that strains associated with pneumonia can be differentiated from strains associated with bacteremia (Figure), despite being non-discriminated at the genomic level. For each model, machine learning techniques followed by co-inertia analysis of proteomic and clinical variables will be applied to visualize the possibly complex relationships between subsets of these groups of variables. Partial least squares regression will be used to model multivariable relationships between predictor and outcome variables. This approach will allow us to assess whether redundant virulence factors compensate each other and add up to determine the virulence potential of S. aureus isolates. Ultimately, the biomarker candidates (or combinations thereof) identified by these analyses will be tested in cellular and animal models, possibly leading to new insights into the more quantitative aspects of S. aureus virulence.