TY - JOUR
T1 - Convergent evolution of zoonotic Brucella species toward the selective use of the pentose phosphate pathway
AU - Machelart, Arnaud
AU - Willemart, Kevin
AU - Zúñiga-Ripa, Amaia
AU - Godard, Thibault
AU - Plovier, Hubert
AU - Wittmann, Christoph
AU - Moriyón, Ignacio
AU - De Bolle, Xavier
AU - Van Schaftingen, Emile
AU - Letesson, Jean-Jacques
AU - Barbier, Thibault
N1 - Funding Information:
The University of Namur provided financial and logistical support. This work was funded by the Fonds de la Recherche Scientifique (FRS-FNRS) "Brucell-cycle" grant (PDR T.0060.15). A.M. was supported by a Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture (FRIA) PhD fellowship from FRS-FNRS. T.B. held an Aspirant Fellowship from FRS-FNRS. Research at the "Universidad de Navarra" was supported by the Institute of Tropical Health (ISTUN) funders (Obra Social la Caixa [LCF/PR/PR13/11080005] and Fundación Caja Navarra, Fundación María Francisca de Roviralta, Ubesol, and Inversiones Garcilaso de la Vega SL). We thank Raquel Conde-Álvarez and Michael Chao for critical reading of this manuscript.
Funding Information:
ACKNOWLEDGMENTS. The University of Namur provided financial and logistical support. This work was funded by the Fonds de la Recherche Scientifique (FRS-FNRS) “Brucell-cycle” grant (PDR T.0060.15). A.M. was supported by a Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA) PhD fellowship from FRS-FNRS. T.B. held an Aspirant Fellowship from FRS-FNRS. Research at the “Universidad de Navarra” was supported by the Institute of Tropical Health (ISTUN) funders (Obra Social la Caixa [LCF/PR/PR13/11080005] and Fundación Caja Navarra, Fundación María Francisca de Roviralta, Ubesol, and Inversiones Garcilaso de la Vega SL). We thank Raquel Conde-Álvarez and Michael Chao for critical reading of this manuscript.
Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.
PY - 2020/10/20
Y1 - 2020/10/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85093824347&partnerID=8YFLogxK
U2 - 10.1073/pnas.2008939117
DO - 10.1073/pnas.2008939117
M3 - Article
C2 - 33020286
VL - 117
SP - 26374
EP - 26381
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 42
ER -