Erythronate utilization activates VdtR regulating its metabolism to promote Brucella proliferation, inducing abortion in mice.

Brucella is an intracellular parasitic bacterium causing zoonosis, which is distributed worldwide and mainly characterized by reproductive disorders. Erythritol is found in allantoic fluid, chorion, and placenta of aborted animals, preferentially utilized by Brucella to cause infertility and abortion. However, the erythritol metabolism-defected mutant was unable to function as a vaccine strain due to its residual virulence. Here, we found that erythronate, an oxidative product of erythritol in the host, was also preferentially utilized by Brucella relying on the function of a deoxyribonucleoside regulator-family transcriptional regulator VdtR. Erythronate utilization activates VdtR regulation of the erythronate metabolic pathway to promote Brucella extracellular proliferation, inducing placentitis/abortion in mice. Double mutations on Brucella erythritol and D-erythronate metabolisms significantly reduced bacterial virulence. This study revealed a novel mechanism of Brucella infection-induced abortion, thus providing a new clue for the study of safer Brucella attenuated vaccines.