BETinCAP

Extracellular polysaccharidic capsules are a virulence factor of many bacteria, which also shapes gene flux and therefore, drives species evolution. This project stems from our novel observation that not all bacteria from a clonal population produce the same amount of capsule. Such phenotypic heterogeneity is an important bacterial feature to increase survival in fluctuating ecosystems, including upon antibiotic exposure, and impacting evolutionary adaptation.

Using Klebsiella pneumoniae as a model system, a nosocomial carbapenamase-producing pathogen causing lung, urinary and liver infections, we aim to: (i) characterize variation in capsule production at the single-cell level across strains and environments, (ii) investigate the mechanisms underlying this phenotypic heterogeneity, (iii) understand its effects on horizontal gene transfer and species evolution, and (iv) address the functional consequences of the cell-to-cell variation in capsule production regarding the infection process and persistence to antibiotic treatment.

This multidisciplinary project will address the phenotypic heterogeneity of a major virulence factor at different levels of cellular organization (from single cell to populations), across time scales (short to microevolution) and across various environments, including the mammalian host. It will provide an overview to how phenotypic heterogeneity in capsule production impacts evolvability and will contribute to identify the bacterial adaptive trends to better predict evolutionary outcomes in the wild and clinical contexts.

Funding