Convergent evolution of zoonotic Brucella species toward the selective use of the pentose phosphate pathway

Arnaud Machelart, Kevin Willemart, Amaia Zúñiga-Ripa, Thibault Godard, Hubert Plovier, Christoph Wittmann, Ignacio Moriyón, Xavier De Bolle, Emile Van Schaftingen, Jean-Jacques Letesson, Thibault Barbier

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

Mechanistic understanding of the factors that govern host tropism remains incompletely understood for most pathogens. Brucella species, which are capable of infecting a wide range of hosts, offer a useful avenue to address this question. We hypothesized that metabolic fine-tuning to intrahost niches is likely an underappreciated axis underlying pathogens' ability to infect new hosts and tropism. In this work, we compared the central metabolism of seven Brucella species by stable isotopic labeling and genetics. We identified two functionally distinct groups, one overlapping with the classical zoonotic species of domestic livestock that exclusively use the pentose phosphate pathway (PPP) for hexose catabolism, whereas species from the second group use mostly the Entner-Doudoroff pathway (EDP). We demonstrated that the metabolic dichotomy among Brucellae emerged after the acquisition of two independent EDP-inactivating mutations in all classical zoonotic species. We then examined the pathogenicity of key metabolic mutants in mice and confirmed that this trait is tied to virulence. Altogether, our data are consistent with the hypothesis that the PPP has been incrementally selected over the EDP in parallel to Brucella adaptation to domestic livestock.

langue originaleAnglais
Pages (de - à)26374-26381
Nombre de pages8
journalProceedings of the National Academy of Sciences of the United States of America
Volume117
Numéro de publication42
Date de mise en ligne précoce2020
Les DOIs
Etat de la publicationPublié - 20 oct. 2020

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