Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 42, Pages 26374-26381Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2008939117
Keywords
Brucella; metabolism; evolution; alpha-Proteobacteria
Categories
Funding
- Fonds de la Recherche Scientifique (FRS-FNRS) Brucell-cycle grant [PDR T.0060.15]
- Fonds pour la Formation a la Recherche dans l'Industrie et dans l'Agriculture (FRIA) PhD fellowship from FRS-FNRS
- FRS-FNRS
- Institute of Tropical Health (ISTUN) (Obra Social la Caixa) [LCF/PR/PR13/11080005]
- Institute of Tropical Health (ISTUN) (Fundacion Caja Navarra)
- Institute of Tropical Health (ISTUN) (Fundacion Maria Francisca de Roviralta)
- Institute of Tropical Health (ISTUN) (Ubesol)
- Institute of Tropical Health (ISTUN) (Inversiones Garcilaso de la Vega SL)
- University of Namur
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available