Barbier, Thibault

De Bolle, Xavier

Godard, Thibault

Letesson, Jean-Jacques

Machelart, Arnaud

Moriyón, Ignacio

Plovier, Hubert

Van Schaftingen, Emile

Willemart, Kevin

Wittmann, Christoph

Zúñiga-Ripa, Amaia

English

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.</p

Repository of the University of Namur

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

https://pure.unamur.be/ws/files/52044708/Machelart_et_al_2020.pdf

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

Abstract

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Repository of the University of Namur

Repository of the University of Namur