Department of Medical Biochemistry and Microbiology

Lionel Guy research group

Degree projects available (mostly bioinformatics). Contact me!

Evolution of host adaptation

Lionel Guy research group
From left to right: Dennis Leenheer, Tiscar Graells, Lionel
Guy, Isa Moreno and Eric Hugoson. 

Our research explores how microorganisms, particularly bacteria, adapt to hosts, and how their relationships evolve over time. The overall goal of our research is to better understand the long- and short-term evolution of host adaptation, and to identify strategies and critical genetic innovations that allow free-living bacteria to adapt to, and then profit from, or live in symbiosis with, eukaryotic hosts.

For their wide variety in host-adaptation strategies and their ecological success, we currently focus on the bacterial order Legionellales, which includes two human pathogens, Legionella and Coxiella. So far, all described species of Legionellales can replicate intracellularly, although their degree of reliance on their host and their host spectrum varies, which makes them especially interesting to study.

Three projects are currently explored:

1. Emergence and evolution of host-adaptation in Legionellales

  • Is the current diversity of Legionellales resulting from a single event of host-adaptation? Was the ancestor of Legionella and Coxiella living inside amoebae?

  • What systems, crucial for host-adaptation, were invented or recruited that paved the way to its current ecological success?

To answer these questions, we rely on advanced bioinformatics, using a comparative genomics approach, tapping into the unexplored diversity of Legionellales. We are using state-of-the art metagenomics and single-cell genomics to harvest organisms that are uncultivable. We aim at reconstructing the ancestors of Legionellales and establish the flow of host-adaptation systems.

courtesy of CDC/Dr. Edwin P. Ewing, Jr

2. Short-term adaptation to the human host in Legionella pneumophila

  • Can short-term adaptation in outbreaks reveal adaptations to human?

By sequencing Legionella pneumophila isolates from legionellosis outbreaks and environmental sources, we identify for short-term mutations that occur inside the accidental human host. By tracing independent mutations in identical genes, we point to adaptations specific to the accidental human host.

3. Inside the amoebal Trojan horse: environmental factors shaping the diversity of intra-amoebal bacteria

(c) Bertelli and Greub 2012

The overall goal of this project is to better understand the environmental factors shaping the diversity and life-style of amoeba-resisting bacteria (ARBs), in particular of Legionella. Amoebae play an important in the ecological success of Legionella, protecting them from bactericidal products, and providing them with a “melting-pot of evolution” where they are exposed to a continuous flow of potentially beneficial genes. Co-evolution between Legionella and its host is thought to have paved the way to the success of Legionella as a human pathogen.

  • What is the genetic diversity inside one single amoebal host? In a population of hosts?

  • What environmental factors influence the diversity of Legionella and other amoeba-resisting bacteria?

  • What is the role of the amoebal host? Are them all equally likely to harbor and disperse intracellular bacteria? How do they respond to environmental factors?

  • What genes and host-adaptation systems are frequently exchanged? Is it possible to identify these transfers as they happen?

In this context, it is very interesting to investigate the effects of the environment on the microbial diversity occurring inside single amoebal hosts and communities of hosts, and to monitor the prevailing gene flux inside them.