TY - JOUR
T1 - Glucose Oxidation to Pyruvate Is Not Essential for Brucella suis Biovar 5 Virulence in the Mouse Model
AU - Lázaro-Antón, Leticia
AU - de Miguel, María Jesús
AU - Barbier, Thibault
AU - Conde-Álvarez, Raquel
AU - Muñoz, Pilar M.
AU - Letesson, Jean Jacques
AU - Iriarte, Maite
AU - Moriyón, Ignacio
AU - Zúñiga-Ripa, Amaia
N1 - Funding Information:
We thank Sara Serrano for her excellent technical assistance. Funding. Research at the University of Navarra was supported by the MINECO (grants AGL2014-58795-C4-1-R and PID2019-107601RA-C32) and the Institute for Tropical Health 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 S.L). Research at URBM was supported by grants from the “Fonds National de la Recherche Scientifique” (FNRS) (Convention No. n° 2.4521.10. from Fonds de la Recherche Scientifique Médicale–FNRS, Belgium), and by the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office. Work at CITA was supported by MINECO (grants AGL2014-58795-C4-1-R and PID2019-107601RA-C32) and “Gobierno de Aragón” (Consolidated Group A14).
Publisher Copyright:
© Copyright © 2021 Lázaro-Antón, de Miguel, Barbier, Conde-Álvarez, Muñoz, Letesson, Iriarte, Moriyón and Zúñiga-Ripa.
PY - 2021/1/14
Y1 - 2021/1/14
N2 - Brucella species cause brucellosis, a worldwide extended zoonosis. The brucellae are related to free-living and plant-associated α2-Proteobacteria and, since they multiply within host cells, their metabolism probably reflects this adaptation. To investigate this, we used the rodent-associated Brucella suis biovar 5, which in contrast to the ruminant-associated Brucella abortus and Brucella melitensis and other B. suis 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, B. suis 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 B. melitensis and B. abortus. 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 B. suis biovar 5 multiplication within host cells, a hypothesis consistent with the lack of classical glycolysis in all Brucella species and of EDP in B. melitensis and B. abortus. 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.
AB - Brucella species cause brucellosis, a worldwide extended zoonosis. The brucellae are related to free-living and plant-associated α2-Proteobacteria and, since they multiply within host cells, their metabolism probably reflects this adaptation. To investigate this, we used the rodent-associated Brucella suis biovar 5, which in contrast to the ruminant-associated Brucella abortus and Brucella melitensis and other B. suis 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, B. suis 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 B. melitensis and B. abortus. 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 B. suis biovar 5 multiplication within host cells, a hypothesis consistent with the lack of classical glycolysis in all Brucella species and of EDP in B. melitensis and B. abortus. 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.
KW - Brucella
KW - Entner-Doudoroff
KW - glucose
KW - metabolism
KW - virulence
UR - http://www.scopus.com/inward/record.url?scp=85102083262&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2020.620049
DO - 10.3389/fmicb.2020.620049
M3 - Article
AN - SCOPUS:85102083262
SN - 1664-302X
VL - 11
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 620049
ER -