Mots-Clés

comparative genomics bacteria-phage interplay immune systems

Description

The phageome’s counter-defensome

Horizontal gene transfer (HGT) enables bacteria to swiftly adapt to new ecological niches and challenges. This process is primarily facilitated by mobile genetic elements (MGEs), such as bacteriophages (phages), plasmids, and transposable elements, which are prevalent in most genomes, often in multiple copies [1-5]. The potential for conflicts arising from the interactions between MGEs and bacteria has driven the evolution of sophisticated defense mechanisms to filter, tame, or inactivate these elements. Indeed, several bacterial defense systems (termed the defensome) have been discovered in the last years, revealing two major groupings based on their components and modes of action: innate (non-specific) and adaptive immune systems. Such findings have been mainly conducted in bacterial species from reference genome databases (e.g., NCBI RefSeq) that are known to overrepresent acute/common human pathogens and organisms that can largely be cultivated in laboratory. In an effort to query the uncharted fraction of environmental microbial diversity that remains uncultured, we recently used culture-independent genome-resolved metagenomics to conduct a large-scale in-depth investigation on the abundance, distribution, and diversity of the defensome in complex bacterial communities from three key environments: soil, marine, and the human gut [6].

We have now reached a key moment in time where despite the discovery of many anti-MGE defense systems, we are lagging behind on our understanding of MGE evasion strategies that counteract them (the counter-defensome). Some examples so far identified in cultivable bacteria include mechanisms deployed to inactivate host immune systems, namely through i) direct binding to immune proteins (anti-RM and anti-CRISPR (Acr) proteins, anti-Gabija, anti-BREX, anti-RecBCD, anti-TA, anti-SIR2); ii) post-translational modification of immune proteins (anti-TA, Acr); and iii) targeting of secondary messengers (anti-CBASS, anti-Pycsar, Acr, anti-Thoeris, anti-Retron). Other counter-defense systems such as anti-AVAST, anti-Hachiman, possess unknown or poorly-characterized mechanisms of action. Here we aim to perform a large-scale mapping of the counter-defensome in a large cohort of virulent and temperate phages isolated from soil, marine and human gut environments. We will investigate their abundance, diversity, co-localization with other defense and counter-defense genes, and their interplay with bacterial hosts.

The ideal candidate will have a strong interest in working in the integration, interpretation and visualization of large biological datasets. Proficiency in UNIX-Linux shell is expected as well as proficiency in at least one of the following programming languages (R/Bioconductor, Python, Perl, C++). Experience in working on high performance computing/cluster platforms will be a plus. The candidate will benefit from a highly dynamic and interdisciplinary environment, including biologists, microbiologists, computer scientists, and bioinformaticians. The Genoscope (French National Sequencing Centre) has a long-standing tradition in the broad field of genomics. After having been one of the players in the human genome project and supporting more than 650 projects serving the national scientific community, it currently focuses on the genomics of environmental organisms (e.g. TARA, BGE, ATLASEA, projects), bacterial flora of the human digestive tract, among others. The M2 contract is expected to start in January-February 2025.

References

1. Oliveira PH et al (2014). Nucleic Acids Res 42(16), 10618-31

2. Oliveira PH et al (2016). Proc Natl Acad Sci USA 113(20), 5658-63

3. Oliveira PH et al (2020). Nat Microbiol 5(1), 166-80

4. Oliveira PH and Fang G (2020). Trends Microbiol 29: 28-40

5. Oliveira PH (2021). mSystems, 6

6. Beavogui et al (2024). Nature Communications 2146