#	Pagina
attuale pagina	/open-h2020/projects/205180/results.html

Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - BactInd (Bacterial cooperation at the individual cell level)

Teaser

Summary

Bacteria play a central role for human health. On the one hand, bacteria are beneficial for us because they form complex consortia in or on our bodies - examples include the gut flora and the skin microbiome - which significantly contribute to our health and well-being. On the other hand, bacteria can also be pathogenic, causing harmful and difficult to treat infections. Research over the last decade has revealed that bacterial social interactions take on important role for establishing both a healthy microbiome and harmful infections. Social interactions include cell-to-cell communication and the secretion of beneficial metabolites that can be shared between cells at the level of the group.

The aim of this ERC project is to study these social interactions at the individual cell level and assess the complexity of microbial cooperation both at the mechanistic and the evolutionary level. This is important and novel because most of our knowledge on social interactions in bacteria is based on measured responses averaged across millions of cells. This contrasts with the fact that bacteria are individuals, interacting with each other at the single cell level. Here we study such single cell interactions and their consequences for bacterial communities. For instance, we aim to uncover how bacteria communicate with one another to reach optimal decisions. Moreover, we ask whether all bacteria in a group behave in the same way, or whether they can coordinate work in the sense that different subgroups of bacteria specialise in different tasks, leading to a simple form of division of labour.

While the primary research objectives are fundamental in nature, we expect the insights gained from this project to have important implications for potential therapeutic applications. For example, it has been proposed that managing social interactions networks between bacteria could be used to strengthen the beneficial microbiome, whereas disrupting social interactions between pathogens could help to manage infections.

Work performed

The main objective of the project is to develop technics and carry out studies to study social interactions between pathogenic bacteria at the single-cell level. During the first 30 months of the project, we were highly successful in achieving our aims. On the technical side, we developed: (i) experimental protocols that allow us to follow behavioural interaction and gene expression patterns of individual bacteria over time using fluorescent microscopy and flow cytometry; (ii) a pipeline for automated high-throughput image analysis; and (iii) a individual-based simulation platform, where we can study bacterial interactions in silico and parameterise our mathematical models with data from experiments. In addition, we established a microscopy protocol to study interactions between pathogenic bacteria within a living host (i.e. the nematode Caenorhabditis elegans).

On the scientific side, we applied these technologies to conduct a number of key studies. Some of the studies have already been completed and published in international peer-reviewed journals, while the majority of studies are still ongoing and will be completed in the second time period of this ERC project. Accomplished projects: (a) We used gene-expression reporters combined with single-cell microscopy to study social interactions in Pseudomonas aeruginosa, an important opportunistic pathogen. In particular, we focussed on the sharing of beneficial compounds secreted by bacteria and shared between group members. We examined the physical boundaries of compound sharing (Weigert and KÃ¼mmerli 2017 Proc B), optimality patterns in compound production and sharing (Schiessl et al. 2019 Evolution), and how group-coordinated behaviour can help in competition against other species (Leinweber et al. 2018 Evolution). In a collaborative project, we applied the same technics and principles to study division of labour in populations of Bacillus subtilis bacteria (Dragos et al. 2018 Current Biology). (b) We published a first paper on multi-level social interactions in bacteria using our in silico simulation platform (Wechsler et al. 2019 J Evol Biol). (c) We used the established host-pathogen system to study how social interactions drive virulence evolution (Granato et al. 2018 ISME J), and how bacteria interact inside the living host (Rezzoagli et al. in press, ISME J).

Final results

Bacteria secrete numerous compounds to cooperate and compete with each other. Compound secretion is involved with virulence and disease. While these aspects are well-studied in batch-culture experiments, we know hardly anything on these interactions at the micrometre scale, thus the level bacteria typically interact with each other. The project aims to close this knowledge gap by delivering results on: (i) the physical scale across which bacteria can exchange secreted compounds; (ii) the scale across which bacteria can sense friendly neighbours or unfriendly competitors and adjust their behaviour accordingly; (iii) whether bacteria in clonal groups all invest in secreted compounds or whether there is the potential for specialization, whereby subgroups invest in different compounds, which are then shared at the level of the group; (iv) how bacteria can coordinate their actions and make meaningful decisions in a speedy way; and (v) whether and how these bacterial community features affect virulence in a host. We believe that the project will push the boundaries of our understanding of sophisticated bacterial interactions, which of interest and relevance to a broad interdisciplinary audience, including scientists and the general public.