Evolution Highlight: Antibody-mediated crosslinking of gut bacteria

The Evolution Highlights series highlights some of the interesting and varied papers published within the last few years in Evolution. The goal of these Evolution Highlights is to let our readers learn more about how the highlighted study came into existence, and to invite the authors to share stories and tips from the perspective of a recently published author. We welcome nominations and self-nominations for the Evolution Highlights. Find out how to submit a paper here.

"Antibody-mediated crosslinking of gut bacteria hinders the spread of antibiotic resistance"
Evolution 73-6: 1077-1088 (2019)
https://onlinelibrary.wiley.com/doi/abs/10.1111/evo.13730

Abstract:
The body is home to a diverse microbiota, mainly in the gut. Resistant bacteria are selected by antibiotic treatments, and once resistance becomes widespread in a population of hosts, antibiotics become useless. Here, we develop a multiscale model of the interaction between antibiotic use and resistance spread in a host population, focusing on an important aspect of within‐host immunity. Antibodies secreted in the gut enchain bacteria upon division, yielding clonal clusters of bacteria. We demonstrate that immunity‐driven bacteria clustering can hinder the spread of a novel resistant bacterial strain in a host population. We quantify this effect both in the case where resistance preexists and in the case where acquiring a new resistance mutation is necessary for the bacteria to spread. We further show that the reduction of spread by clustering can be countered when immune hosts are silent carriers, and are less likely to get treated, and/or have more contacts. We demonstrate the robustness of our findings to including stochastic within‐host bacterial growth, a fitness cost of resistance, and its compensation. Our results highlight the importance of interactions between immunity and the spread of antibiotic resistance, and argue in the favor of vaccine‐based strategies to combat antibiotic resistance.

Evolution Highlight by Anne-Florence Bitbol and Claude Loverdo (joint interview)
Institute of Bioengineering, School of Life Sciences, EPFL (Anne-Florence Bitbol)
Laboratoire Jean Perrin, Institut de Biologie Paris-Seine, CNRS & Sorbonne Universite (Claude Loverdo)

What gave you the idea for this study?

This strongly collaborative project arose from discussions between Claude and Anne-Florence. One of Anne-Florence's research goals is to quantify the impact of population structure on evolution. Claude's main research theme is to understand the interaction between the immune system and the bacteria in the gut. This project unites these two fields and our strengths. Specifically, an important recent finding in immunology, from Emma Slack's laboratory, and to which Florence and Claude contributed, is that antibodies secreted in the gut enchain daughter bacteria upon replication. Because clusters of bacteria cannot interact normally with the gut surface, this protects the host. But this clustering also gives a specific structure to the bacterial population, which can have a strong impact on its evolution. We thus decided to investigate the impact of this immunity-driven clustering on the evolution of antibiotic resistance.

What was the big question you were trying to ask and why was it exciting?

It was really exciting to develop models to find out possible new implications on evolution of a recent experimental discovery in immunology.

Did your work take you to any interesting locations? If so, what were they like?

This work involves analytical calculations and numerical simulations, so we only collected data from computers!

Did you have to learn any new analytical techniques for this study?

We combined our expertises for this work. In particular, Claude already had expertise in the formalism of branching processes. Meanwhile, Anne-Florence had already worked on modeling antibiotic resistance evolution and on population structure. Florence had acquired experience in numerical calculations and Loïc in numerical simulations. We all learned from one another in the process.

What was your writing process like?

As the rest of the project, the writing process was very collaborative, with all authors participating. Sometimes we could see different parts of our shared draft changing simultaneously and quite rapidly! It was great, but one small practical difficulty was to all agree on the same notations.

What was the review / revision process like?

The review and revision process was really nice and smooth for this paper, and we got great suggestions from both the reviewers and the editor. Sometimes this process can be painful, but for this paper it was definitely a pleasant one, and we really feel that the paper improved as a result.

Was this study collaborative with other groups? If so, what was valuable about that experience?

Again, this project was deeply collaborative, and we now continue to work together on related topics. It is the first paper involving both Claude and Anne-Florence. So this was really a great experience, and hopefully the start of a long collaboration. Crucially, we worked with our two PhD students: Florence (not to be confused with Anne-Florence!), who was Claude's PhD student, and Loïc, who is Anne-Florence's PhD student. They are joint first authors on this paper, and their contributions were amazing, both concerning analytical calculations and numerical simulations. They both proposed important ideas and went far beyond what we first thought of. So this was really a great collective project!

What do you think will be the lasting impact of this study?

We demonstrated that the clustering of bacteria driven by immunity hinders the emergence of antibiotic resistance. This is because clustering leads to a decrease in the bacterial diversity transmitted from one host to the next. We hope that our results will have practical impact because they shed light on an interesting interplay between vaccination and antibiotic treatment. Specifically, vaccination could reduce antibiotic resistance through this effect.