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

• DOI: 10.1073/pnas.1808016116
• Publication Date: 2019-01-19T01:36:00Z
• Authors: Laura Gomez-Valero; Christophe Rusniok; Danielle Carson; Sonia Mondino; Ana Elena Pérez-C...; Monica Rolando; Shivani Pasricha; Sandra Reuter; Jasmin Demirtas; Johannes Crumbach; Stephane Descorps...; Elizabeth L. Hart...; Sophie Jarraud; Gordon Dougan; Gunnar N. Schroeder; Gad Frankel; Carmen Buchrieser
• Keywords: Rab; Legionella

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