Possible biased virulence attenuation in the Senegal strain of Ehrlichia ruminantium by ntrX gene conversion from an inverted segmental duplication

Gordon Jonathan, Oliva Chavez Adela Sarahi, Martinez Dominique, Vachiéry Nathalie, Meyer Damien. 2023. Possible biased virulence attenuation in the Senegal strain of Ehrlichia ruminantium by ntrX gene conversion from an inverted segmental duplication. PloS One, 18 (2):e0266234, 17 p.

Url - jeu de données - Entrepôt autre : https://www.ncbi.nlm.nih.gov/nuccore/?term=GCA_002019755.1

Liste HCERES des revues (en SHS) : oui

Thème(s) HCERES des revues (en SHS) : Psychologie-éthologie-ergonomie; Staps

Résumé : Ehrlichia ruminantium is a tick-borne intracellular pathogen of ruminants that causes heartwater, a disease present in Sub-saharan Africa, islands in the Indian Ocean and the Caribbean, inducing significant economic losses. At present, three avirulent strains of E. ruminantium (Gardel, Welgevonden and Senegal isolates) have been produced by a process of serial passaging in mammalian cells in vitro, but unfortunately their use as vaccines do not offer a large range of protection against other strains, possibly due to the genetic diversity present within the species. So far no genetic basis for virulence attenuation has been identified in any E. ruminantium strain that could offer targets to facilitate vaccine production. Virulence attenuated Senegal strains have been produced twice independently, and require many fewer passages to attenuate than the other strains. We compared the genomes of a virulent and attenuated Senegal strain and identified a likely attenuator gene, ntrX, a global transcription regulator and member of a two-component system that is linked to environmental sensing. This gene has an inverted partial duplicate close to the parental gene that shows evidence of gene conversion in different E. ruminantium strains. The pseudogenisation of the gene in the avirulent Senegal strain occurred by gene conversion from the duplicate to the parent, transferring a 4 bp deletion which is unique to the Senegal strain partial duplicate amongst the wild isolates. We confirmed that the ntrX gene is not expressed in the avirulent Senegal strain by RT-PCR. The inverted duplicate structure combined with the 4 bp deletion in the Senegal strain can explain both the attenuation and the faster speed of attenuation in the Senegal strain relative to other strains of E. ruminantium. Our results identify nrtX as a promising target for the generation of attenuated strains of E. ruminantium by random or directed mutagenesis that could be used for vaccine production.

Mots-clés Agrovoc : Ehrlichia ruminantium

Mots-clés libres : Virulence factors, Gene expression, Ehrlichia, Gene conversion, Gene regulation, Host cells, Regulator genes, Endothelial cells

Classification Agris : L72 - Organismes nuisibles des animaux
L73 - Maladies des animaux

Champ stratégique Cirad : CTS 4 (2019-) - Santé des plantes, des animaux et des écosystèmes

Agences de financement européennes : European Regional Development Fund, European Commission

Programme de financement européen : FP7

Projets sur financement : (EU) Surveillance, diagnosis, control and impact of infectious diseases of humans, animals and plants in tropical islands, (EU) 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

Auteurs et affiliations

• Gordon Jonathan, CIRAD-BIOS-UMR PVBMT (REU)
• Oliva Chavez Adela Sarahi, INRAE (FRA)
• Martinez Dominique, CIRAD-DGDRD-DRAG (GLP)
• Vachiéry Nathalie, CIRAD-BIOS-UMR ASTRE (FRA)
• Meyer Damien, CIRAD-BIOS-UMR ASTRE (GLP) ORCID: 0000-0003-2735-176X - auteur correspondant

Source : Cirad-Agritrop (https://agritrop.cirad.fr/605086/)

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