A novel gluconeogenic route enables efficient use of erythritol in zoonotic Brucella

作者：Leticia Lázaro-Antón, Maria Veiga‐da‐Cunha, Aitor Elizalde-Bielsa, Nathalie Chevalier, Raquel Conde-Álvarez, Maite Iriarte, Jean‐Jacques Letesson, Ignacio Moriyón, Emile Van Schaftingen, Amaia Zúñiga-Ripa · 发表于：Frontiers in Veterinary Science · 年份：2024 · DOI：10.3389/fvets.2024.1328293 · 被引用次数：5 · 研究领域：Brucella: diagnosis, epidemiology, treatment、Burkholderia infections and melioidosis、Galectins and Cancer Biology

Brucellosis is a worldwide extended zoonosis caused by pathogens of the genus Brucella. While most B. abortus, B. melitensis, and B. suis biovars grow slowly in complex media, they multiply intensely in livestock genitals and placenta indicating high metabolic capacities. Mutant analyses in vitro and in infection models emphasize that erythritol (abundant in placenta and genitals) is a preferred substrate of brucellae, and suggest hexoses, pentoses, and gluconeogenic substrates use in host cells. While Brucella sugar and erythritol catabolic pathways are known, growth on 3–4 carbon substrates persists in Fbp- and GlpX-deleted mutants, the canonical gluconeogenic fructose 1,6-bisphosphate (F1,6bP) bisphosphatases. Exploiting the prototrophic and fast-growing properties of B. suis biovar 5, we show that gluconeogenesis requires fructose-bisphosphate aldolase (Fba); the existence of a novel broad substrate bisphosphatase (Bbp) active on sedoheptulose 1,7-bisphosphate (S1,7bP), F1,6bP, and other phosphorylated substrates; that Brucella Fbp unexpectedly acts on S1,7bP and F1,6bP; and that, while active in B. abortus and B. melitensis, GlpX is disabled in B. suis biovar 5. Thus, two Fba-dependent reactions (dihydroxyacetone-phosphate + glyceraldehyde 3-phosphate ⇌ F1,6bP; and dihydroxyacetone-phosphate + erythrose 4-phosphate ⇌ S1,7bP) can, respectively, yield fructose 6-phosphate and sedoheptulose 7-phosphate for classical gluconeogenesis and the Pentose Phosphate Shunt (PPS), the...