Comparative genomics of the zoonotic pathogen Ehrlichia chaffeensis reveals candidate type IV effectors and putative host cell targets

Noroy Christophe, Meyer Damien. 2017. Comparative genomics of the zoonotic pathogen Ehrlichia chaffeensis reveals candidate type IV effectors and putative host cell targets. Frontiers in Cellular and Infection Microbiology, 6 (204), 15 p.

Journal article ; Article de revue à facteur d'impact
Published version - Anglais
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Quartile : Q2, Sujet : MICROBIOLOGY / Quartile : Q2, Sujet : IMMUNOLOGY

Abstract : During infection, some intracellular pathogenic bacteria use a dedicated multiprotein complex known as the type IV secretion system to deliver type IV effector (T4E) proteins inside the host cell. These T4Es allow the bacteria to evade host defenses and to subvert host cell processes to their own advantage. Ehrlichia chaffeensis is a tick-transmitted obligate intracellular pathogenic bacterium, which causes human monocytic ehrlichiosis. Using comparative whole genome analysis, we identified the relationship between eight available E. chaffeensis genomes isolated from humans and show that these genomes are highly conserved. We identified the candidate core type IV effectome of E. chaffeensis and some conserved intracellular adaptive strategies. We assigned the West Paces strain to genetic group II and predicted the repertoires of T4Es encoded by E. chaffeensis genomes, as well as some putative host cell targets. We demonstrated that predicted T4Es are preferentially distributed in gene sparse regions of the genome. In addition to the identification of the two known type IV effectors of Anaplasmataceae, we identified two novel candidates T4Es, ECHLIB_RS02720 and ECHLIB_RS04640, which are not present in all E. chaffeensis strains and could explain some variations in inter-strain virulence. We also identified another novel candidate T4E, ECHLIB_RS02720, a hypothetical protein exhibiting EPIYA, and NLS domains as well as a classical type IV secretion signal, suggesting an important role inside the host cell. Overall, our results agree with current knowledge of Ehrlichia molecular pathogenesis, and reveal novel candidate T4Es that require experimental validation. This work demonstrates that comparative effectomics enables identification of important host pathways targeted by the bacterial pathogen. Our study, which focuses on the type IV effector repertoires among several strains of E. chaffeensis species, is an original approach and provides rational putative targets for the design of alternative therapeutics against intracellular pathogens. The collection of putative effectors of E. chaffeensis described in our paper could serve as a roadmap for future studies of the function and evolution of effectors. (Résumé d'auteur)

Mots-clés Agrovoc : Ehrlichia, Agent pathogène, Génome, Génétique des populations, Protéine bactérienne, Transmission des maladies, Effecteur moléculaire, Relation hôte pathogène, Maladie transmissible par tiques, Épidémiologie, Génie génétique, Genre humain, Logiciel, Bioinformatique, génomique, Ehrlichia chaffeensis

Classification Agris : L72 - Pests of animals
L73 - Animal diseases
000 - Other themes

Champ stratégique Cirad : Axe 4 (2014-2018) - Santé des animaux et des plantes

Agence(s) de financement européenne(s) : European Commission

Programme de financement européen : FP7

Projet(s) de financement européen(s) : One Health approach to integrate Guadeloupe research on vector-borne and emerging diseases in the ERA: from characterization of emergence mechanisms to innovative approaches for prediction and control

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