Skip to Main content Skip to Navigation
Journal articles

More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells

Abstract : The genus Legionella comprises 65 species, among which Legionella pneumophila is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental human pathogen, we have functionally analyzed 80 Legionella genomes spanning 58 species. Uniquely, an immense repository of 18,000 secreted proteins encoding 137 different eukaryotic-like domains and over 200 eukaryotic-like proteins is paired with a highly conserved type IV secretion system (T4SS). Specifically, we show that eukaryotic Rho- and Rab-GTPase domains are found nearly exclusively in eukaryotes and Legionella Translocation assays for selected Rab-GTPase proteins revealed that they are indeed T4SS secreted substrates. Furthermore, F-box, U-box, and SET domains were present in >70% of all species, suggesting that manipulation of host signal transduction, protein turnover, and chromatin modification pathways are fundamental intracellular replication strategies for legionellae. In contrast, the Sec-7 domain was restricted to L. pneumophila and seven other species, indicating effector repertoire tailoring within different amoebae. Functional screening of 47 species revealed 60% were competent for intracellular replication in THP-1 cells, but interestingly, this phenotype was associated with diverse effector assemblages. These data, combined with evolutionary analysis, indicate that the capacity to infect eukaryotic cells has been acquired independently many times within the genus and that a highly conserved yet versatile T4SS secretes an exceptional number of different proteins shaped by interdomain gene transfer. Furthermore, we revealed the surprising extent to which legionellae have coopted genes and thus cellular functions from their eukaryotic hosts, providing an understanding of how dynamic reshuffling and gene acquisition have led to the emergence of major human pathogens.
Document type :
Journal articles
Complete list of metadatas

Cited literature [45 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-02563435
Contributor : Isabelle Hoffmann <>
Submitted on : Tuesday, June 16, 2020 - 9:41:46 AM
Last modification on : Friday, June 19, 2020 - 1:32:02 AM

File

2019 PNAS_Gomez-Valero.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Laura Gomez-Valero, Christophe Rusniok, Danielle Carson, Sonia Mondino, Ana Elena Pérez-Cobas, et al.. More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2019, 116 (6), pp.2265-2273. ⟨10.1073/pnas.1808016116⟩. ⟨pasteur-02563435⟩

Share

Metrics

Record views

62

Files downloads

80