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Glucose Oxidation to Pyruvate Is Not Essential for Biovar 5 Virulence in the Mouse Model. | LitMetric

AI Article Synopsis

  • - Brucellosis is a worldwide zoonosis caused by Brucella species, which are adapted to survive and multiply inside host cells, influencing their metabolic pathways.
  • - The study focused on biovar 5, a fast-growing species, and examined the effects of disrupting key enzymes in the Entner-Doudoroff pathway, revealing that mutants with impaired pathways showed reduced growth in glucose and other sugars.
  • - Despite the growth challenges, the triple mutant was not less virulent in mice, suggesting that Brucella biovar 5 can rely on alternative pathways for energy and growth within host cells, particularly favoring shorter carbon substrates rather than typical sugars.

Article Abstract

species cause brucellosis, a worldwide extended zoonosis. The brucellae are related to free-living and plant-associated α2- and, since they multiply within host cells, their metabolism probably reflects this adaptation. To investigate this, we used the rodent-associated biovar 5, which in contrast to the ruminant-associated and and other biovars, is fast-growing and conserves the ancestral Entner-Doudoroff pathway (EDP) present in the plant-associated relatives. We constructed mutants in Edd (glucose-6-phosphate dehydratase; first EDP step), PpdK (pyruvate phosphate dikinase; phosphoenolpyruvate ⇌ pyruvate), and Pyk (pyruvate kinase; phosphoenolpyruvate → pyruvate). In a chemically defined medium with glucose as the only C source, the Edd mutant showed reduced growth rates and the triple Edd-PpdK-Pyk mutant did not grow. Moreover, the triple mutant was also unable to grow on ribose or xylose. Therefore, biovar 5 sugar catabolism proceeds through both the Pentose Phosphate shunt and EDP, and EDP absence and exclusive use of the shunt could explain at least in part the comparatively reduced growth rates of and . The triple Edd-PpdK-Pyk mutant was not attenuated in mice. Thus, although an anabolic use is likely, this suggests that hexose/pentose catabolism to pyruvate is not essential for biovar 5 multiplication within host cells, a hypothesis consistent with the lack of classical glycolysis in all species and of EDP in and . These results and those of previous works suggest that within cells, the brucellae use mostly 3 and 4 C substrates fed into anaplerotic pathways and only a limited supply of 5 and 6 C sugars, thus favoring the EDP loss observed in some species.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840955PMC
http://dx.doi.org/10.3389/fmicb.2020.620049DOI Listing

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