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Courtine, D.

Publications and source records attributed to Courtine, D..

4 recordsLinked to original sources

Thermococcales pangenome uncovers new genera and modular evolution.

The order Thermococcales is unusual among Archaea in being known primarily from hundreds of lab-cultured isolates rather than metagenome-assembled genomes. Such cultivation is powerful for comparative genomics, allowing access to complete closed genomes rather than fragmented assemblies. We analysed 122 complete genomes, comprising all publicly available type species plus 67 new isolates, as a single pangenome. A combination of genome-scale metrics resolved 70 species across five genus-level clades, two proposed here as the new genera Oleococcus and Piezococcus, in addition to the canonical Pyrococcus, Palaeococcus, and Thermococcus. Only 6.1% of the 21,490 gene families are persistent, yet these contribute over half the genes in any genome. We observe that accessory functions, such as amino-acid biosynthesis, often behave modularly, being gained and lost as intact cassettes from genus-specific chromosomal loci. Combined with 114 mobile genetic elements, 72 of which are integrated in the chromosome at conserved tRNA genes, we find that Thermococcales genomes accommodate rapid horizontal turnover through a constrained chromosomal architecture.

genomics↗

Increased pathogenicity of the nematophagous fungus Drechmeria coniospora following long-term laboratory culture.

Domestication provides a window into adaptive change. Over the course of 2 decades of laboratory culture, a strain of the nematode-specific fungus Drechmeria coniospora became more virulent during its infection of Caenorhabditis elegans. Through a close comparative examination of the genome sequences of the original strain and its more pathogenic derivative, we identified a small number of non-synonymous mutations in protein-coding genes. In one case, the mutation was predicted to affect a gene involved in hypoxia resistance and we provide direct corroborative evidence for such an effect. The mutated genes with functional annotation were all predicted to impact the general physiology of the fungus and this was reflected in an increased in vitro growth, even in the absence of C. elegans. While most cases involved single nucleotide substitutions predicted to lead to a loss of function, we also observed a predicted restoration of gene function through deletion of an extraneous tandem repeat. This latter change affected the regulatory subunit of a cAMP-dependent protein kinase. Remarkably, we also found a mutation in a gene for a second protein of the same, protein kinase A, pathway. Together, we predict that they result in a stronger repression of the pathway for given levels of ATP and adenylate cyclase activity. Finally, we also identified mutations in a few lineage-specific genes of unknown function that are candidates for factors that influence virulence in a more direct manner.

evolutionary biology↗

Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences.

Animals and plants need to defend themselves from pathogen attack. Their defences drive innovation in virulence mechanisms, leading to never-ending cycles of co-evolution in both hosts and pathogens. A full understanding of host immunity therefore requires examination of pathogen virulence strategies. Here, we take advantage of the well-studied innate immune system of Caenorhabditis elegans to dissect the action of two virulence factors from its natural fungal pathogen Drechmeria coniospora. We show that these two enterotoxins have strikingly different effects when expressed individually in the nematode epidermis. One is able to interfere with diverse aspects of host cell biology, altering vesicle trafficking and preventing the key STAT-like transcription factor STA-2 from activating defensive antimicrobial peptide gene expression. The second, potentially as a consequence of a host surveillance mechanism, increases STA-2 levels in the nucleus, modifies the nucleolus, and causes increased defence gene expression. Our results highlight the remarkably complex and potentially antagonistic mechanisms that come into play in the interaction between co-evolved hosts and pathogens.

microbiology↗

Long-read only assembly of Drechmeria coniospora genomes reveals widespread chromosome plasticity and illustrates the limitations of current nanopore methods

Long read sequencing is increasingly being used to determine eukaryotic genomes. We used nanopore technology to generate chromosome-level assemblies for 3 different strains of Drechmeria coniospora, a nematophagous fungus used extensively in the study of innate immunity in Caenorhabditis elegans. One natural geographical isolate demonstrated high stability over decades, whereas a second isolate, not only had a profoundly altered genome structure, but exhibited extensive instability. We conducted an in-depth analysis of sequence errors within the 3 genomes and established that even with state-of-the-art tools, nanopore methods alone are insufficient to generate eukaryotic genome sequences of sufficient accuracy to merit inclusion in public databases.

genomics↗