[604] Genomics and Microbiota

Staphylococcus aureus

Our study of Staphylococcus aureus focuses on identifying the virulence mechanisms conferred by bacteriophages, as well as their ability to form dormant bacterial cells, characteristic of chronic disease and conducive to relapses.

Clinical metagenomic

Our major research axes address different clinical challenges related to bacteria colonizing the human body, using metataxonomic, metagenomic and genomic approaches, which rely on next-generation sequencing (NGS).

The metataxonomic approach is based on sequencing of phylogenetic/taxonomic markers (mostly the 16S rRNA gene) while metagenomics uses random sequencing of DNA directly recovered from samples.  Our studies aim to identify associations between taxonomic composition and various diseases (such as cancer, infections, neurologic, hepatic and renal disorders) or exposure to specific treatments (including probiotics, antibiotics and other medications, intensive care, dietary factors, etc.). Beyond taxonomic composition, we explore gene functions, with a particular emphasis on antibiotic resistance. Our projects predominantly focus on the microbiota of the intestine, oral cavity, and respiratory system.

Our second major focus is clinical metagenomics in the context of infectious diseases. This involves utilizing NGS and bioinformatics tools to identify DNA fragments from pathogenic microorganisms, particularly bacteria and fungi, in clinical samples. Our efforts, and especially that of Dr Mikael Tognon,  in this domain are dedicated to (i) optimizing procedures for selectively eliminating human DNA from clinical samples, aiming to enhance the pathogen-to-human DNA ratio and provide a more comprehensive characterization of the microbiota members; (ii) quantifying pathogens using calibrators, such as cells from organisms not part of the human microbiota; and (iii) refining reference databases and automating bioinformatics pipelines for the analysis of NGS data.

Genomics studies of pathogen isolates of interest, based on NGS, provide the highest resolution for molecular typing and enable the identification of acquired antibiotic resistance genes and the presence of mutations conferring resistance. This approach allows for addressing genetic and phylogenetic relatedness between strains, which may help in identifying potential routes of spatial and temporal transmission of strains and their antibiotic resistance determinants during outbreaks in hospitals or communities, or on a broader scale, such as transmissions to humans from animals, foods, or the environment. We actively participate in the working group involved in the development of the Swiss Pathogen Surveillance Platform (SPSP.ch), whose aim is to harmonize NGS practices within Swiss clinical microbiology laboratories and implement a molecular surveillance platform allowing integration of high-resolution whole genome sequencing (WGS) typing data and epidemiological information. Additionally, we are members of the IICU Consortium (Personalized, data-driven prediction and assessment of Infection-related outcomes in Swiss ICUs), a collaborative initiative set to transform the landscape of predicting infection-related outcomes in intensive care units.