The EvolutioNary role of CAPSULes in bacterial AdaptaTION – ENCAPSULATION

Capsules are the outermost layer of some bacteria and the first contact between the cell and its environment. They allow bacteria to withstand numerous stresses, and to resist to antibiotics. Our previous research showed that capsulated bacteria are better colonizers and are dominant in most environments. By favouring colonization and adaptation to harsh environments, the conditions of expression of the capsule are the same that favour high rates of genetic exchange. Hence, one would expect a positive association between the presence of capsules and the rates of horizontal gene transfer and homologous recombination.  Instead, it has been often proposed that capsules hinder the transfer of genetic information between cells, presumably because they constitute a physical barrier to DNA acquisition. Yet, our preliminary studies show that species encoding capsules have more, not fewer, mobile genetic elements, including prophages and plasmids. These surprising results spurred this proposal for a research to elucidate the role that capsules play in the evolution of bacterial species. 

The main hypothesis driving this proposal is that bacterial capsules play an important role in bacterial adaptation. Capsules are beneficial to cells, but are also expected to impose a significant cost to the cell. However, the precise cost of capsule production in relevant environments has rarely been evaluated and most eco-evolutionary questions concerning capsules have yet to be explored.

Using Klebsiella pneumoniae as a model system, a major multi-drug resistant (MDR) nosocomial pathogen causing lung, urinary and liver infections, this project aims to:
(i) Quantify the short-term fitness and metabolic costs of capsule production by generating a panel of capsule null mutants and assessing their competitive index against their capsulated variant, and we will correlate this with capsule thickness and expression levels of genes involved in its production and secretion. In parallel, we will assess the potential beneficial role of capsules as a nutrient reservoir under starvation conditions.
(ii) Understand how capsules affect bacterial adaptation to new environments through hundreds of generations (micro-evolution). We will undertake a mid-term evolution experiment and analyze the mutations that emerge through time across the different environments and compare them to those observed in natural populations.
(iii) Determine the role of capsules in genetic transfer and the long-term evolution of genomes (macro-evolution), by calculating rates of genetic transfer within species with and without capsules and the accumulation of mobile genetic elements and antibiotic resistance genes in genomes.

This multidisciplinary project combining experimental and computational biology will provide a global overview, at all time-scales, of the interplay between capsules and genetic transfer and how it affects the short, mid and long term genome evolution. It will also provide a comprehensive analysis of the costs and benefits of capsule production across a broad range of environments which reflect the tropism of a worrisome facultative pathogen. Ultimately, this project will contribute to develop methods to study adaptive trends of bacteria and to better predict evolutionary outcomes in the wild.