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

ABSTRACT: 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.

SUBMITTER: Machelart A

PROVIDER: S-EPMC7584911 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Machelart Arnaud A Willemart Kevin K Zúñiga-Ripa Amaia A Godard Thibault T Plovier Hubert H Wittmann Christoph C Moriyón Ignacio I De Bolle Xavier X Van Schaftingen Emile E Letesson Jean-Jacques JJ Barbier Thibault T

Proceedings of the National Academy of Sciences of the United States of America 20201005 42

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 is ...[more]

PMID: 33020286

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Project description:Erythritol is an important nutrient for several α-2 Proteobacteria, including N2-fixing plant endosymbionts and Brucella, a worldwide pathogen that finds this four-carbon polyol in genital tissues. Erythritol metabolism involves phosphorylation to L-erythritol-4-phosphate by the kinase EryA and oxidation of the latter to L-3-tetrulose 4-phosphate by the dehydrogenase EryB. It is accepted that further steps involve oxidation by the putative dehydrogenase EryC and subsequent decarboxylation to yield triose-phosphates. Accordingly, growth on erythritol as the sole C source should require aldolase and fructose-1,6-bisphosphatase to produce essential hexose-6-monophosphate. However, we observed that a mutant devoid of fructose-1,6-bisphosphatases grew normally on erythritol and that EryC, which was assumed to be a dehydrogenase, actually belongs to the xylose isomerase superfamily. Moreover, we found that TpiA2 and RpiB, distant homologs of triose phosphate isomerase and ribose 5-phosphate isomerase B, were necessary, as previously shown for Rhizobium. By using purified recombinant enzymes, we demonstrated that L-3-tetrulose-4-phosphate was converted to D-erythrose 4-phosphate through three previously unknown isomerization reactions catalyzed by EryC (tetrulose-4-phosphate racemase), TpiA2 (D-3-tetrulose-4-phosphate isomerase; renamed EryH), and RpiB (D-erythrose-4-phosphate isomerase; renamed EryI), a pathway fully consistent with the isotopomer distribution of the erythrose-4-phosphate-derived amino acids phenylalanine and tyrosine obtained from bacteria grown on (13)C-labeled erythritol. D-erythrose-4-phosphate is then converted by enzymes of the pentose phosphate pathway to glyceraldehyde 3-phosphate and fructose 6-phosphate, thus bypassing fructose-1,6-bisphosphatase. This is the first description to our knowledge of a route feeding carbohydrate metabolism exclusively via D-erythrose 4-phosphate, a pathway that may provide clues to the preferential metabolism of erythritol by Brucella and its role in pathogenicity.

Dataset Information

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

Publications

Convergent evolution of zoonotic <i>Brucella</i> species toward the selective use of the pentose phosphate pathway.

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