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

The genus comprises 65 species, among which is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental human pathogen, we have functionally analyzed 80 genomes spanning 58 species. Uniquely, an immense repository of 18,000 secreted proteins encodin...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 6; p. 2265
Main Authors: Gomez-Valero, Laura, Rusniok, Christophe, Carson, Danielle, Mondino, Sonia, Pérez-Cobas, Ana Elena, Rolando, Monica, Pasricha, Shivani, Reuter, Sandra, Demirtas, Jasmin, Crumbach, Johannes, Descorps-Declere, Stephane, Hartland, Elizabeth L, Jarraud, Sophie, Dougan, Gordon, Schroeder, Gunnar N, Frankel, Gad, Buchrieser, Carmen
Format: Journal Article
Language:English
Published: United States 05.02.2019
Subjects:
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
Bacterial Secretion Systems - genetics
Computational Biology - methods
Evolution, Molecular
Genome, Bacterial
Genomics - methods
Humans
Intracellular Space - microbiology
Legionella - classification
Legionella - physiology
Legionellosis - microbiology
Phylogeny
Protein Domains
Legionella
human pathogen
horizontal gene transfer
coevolution
protozoa
ISSN:1091-6490, 1091-6490
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Summary:The genus comprises 65 species, among which is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental human pathogen, we have functionally analyzed 80 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 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 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.
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1808016116