New PATHOCOM project aims to discover how pathogens team up to cause disease

A Pseudomonas bacteria entering a plant leaf. Image courtesy of the Max Planck Institute for Developmental Biology
A Pseudomonas bacteria entering a plant leaf. Image courtesy of the Max Planck Institute for Developmental Biology.

Pathogens are the cause of many serious diseases in plants, animals and humans, but what is less obvious is that pathogens rarely act on their own. As one example, the majority of deaths during the 1918/1919 flu pandemic were not caused by the influenza virus, but rather by complications from bacterial pneumonia. How pathogens interact to displace other, harmless microbes and, in consequence, injure or even kill their hosts is thus a question with broad relevance in many systems.

An international team of researchers from Germany, France and the U.S. has been awarded one of the prestigious and highly competitive Synergy Grants of the European Research Council (ERC) to study this question. The effort will be led by Detlef Weigel, PhD, from the Max Planck Institute for Developmental Biology in Tübingen; Fabrice Roux, PhD, from CNRS in Toulouse; and Joy Bergelson, PhD, Chair of the Department of Ecology and Evolution at the University of Chicago.

Understanding pathogen interaction

The goal of the PATHOCOM project is to discover the frequency of different types of interactions between microbes in complex microbial communities, especially cooperation and competition, and how ecology and genetics alter these interactions. The team seeks to answer questions such as: What are the key drivers of pathogens' success, and how do pathogens interact with each other and the environment within their host? Similar to understanding a massive marathon race with different teams and individual competitors, PATHOCOM aims to learn who among the pathogens competes with whom, and who among them is teaming up with whom to win.

These questions will be addressed using the plant Arabidopsis thaliana and its microbial pathogens. The transatlantic research team will infect plants with almost 200,000 different combinations of pathogenic and non-pathogenic bacterial strains, and measure who is helped by co-infection and who is not. In parallel, thousands of plants from natural sites in the U.S., France and Germany will be studied to learn how the patterns discovered in the lab compare to real-world data. The connection between the two lines of research will come from sophisticated mathematical models that allow the prediction of complex microbial communities starting from knowledge of interactions tested in the lab.

The experimental hurdles are daunting, given that 300 different bacterial strains can, in theory, assemble into more combinations than there are atoms in the universe. The key to meeting this challenge lies in innovative CRISPR-Cas9-based methods to “barcode” both bacteria and plants, which allow for ultra-high-throughput analysis of infection trials.

Importantly, the PATHOCOM scientists will not only perform experiments under artificial lab conditions, but will also carry out field trials with genetically modified plants and bacteria. Because current regulations on the use of genetically modified plant species make it difficult to conduct such studies in Europe, these experiments in real-world environments will be carried out in the U.S. at a dedicated site at the University of Chicago.

Innovative steps toward pathogen control

“In a year like this, it’s unnecessary to stress the importance of understanding what allows pathogens to damage their hosts. There are many factors that determine pathogen success, but an essential factor is often the presence of other pathogens. We must understand what determines the success of pathogens in complex microbial communities if we want to develop new interventions to control them,” said Weigel, corresponding principal investigator for the grant.

Bergelson added, “The discovery of key ecological and genetic drivers of pathogen success will be a first step to help transform plant-pathogen studies into a predictive science that can be applied to other pathogens and hosts.”

The researchers believe this project will not only improve our understanding of human host/pathogen interactions, but may also lead to new technologies for agriculture. “Such knowledge can in turn become the foundation for developing radically new ways of preventing pathogens from taking over microbial communities and causing disease, with the ambitious future goal of developing personalized agriculture,” said team member Fabrice Roux.

This project will be funded by ERC Synergy Grant #9514444.

This story is courtesy of the Max Planck Institute for Developmental Biology in Tübingen.