Erythritol triggers expression of virulence traits in Brucella melitensis

Abstract

Erythritol is a four-carbon sugar preferentially utilized by Brucella spp. The presence of erythritol in the placentas of goats, cows, and pigs has been used to explain the localization of Brucella to these sites and the subsequent accumulation of large amounts of bacteria, eventually leading to abortion. Here we show that B. melitensis will also localize to an artificial site of erythritol within a mouse, providing a potential model system to study the pathogenesis of Brucella abortion. Immunohistological staining of the sites of erythritol within infected mice indicated a higher than expected proportion of extracellular bacteria. Ensuing experiments suggested intracellular B. melitensis was unable to replicate within macrophages in the presence of erythritol and that erythritol was able to reach the site of intracellular bacteria. The intracellular inhibition of growth was found to encourage the bacteria to replicate extracellularly rather than intracellularly, a particularly interesting development in Brucella pathogenesis. To determine the effect of erythritol on expression of B. melitensis genes, bacteria grown either with or without erythritol were analyzed by microarray. Two major virulence pathways were up-regulated in response to exposure to erythritol (the type IV secretion system VirB and flagellar proteins), suggesting a role for erythritol in virulence.

Brucella seropositivity in chicken and risk factors for Brucella infection at the animal-human interface in Anambra State, Nigeria

“…Brucella species have affinity for the female reproductive organ due to the production of erythritol, a 4-carbon sugar in these tissues that stimulate their growth and proliferation [33]. Moreover, female chicken is generally reared for longer periods in the farm than cocks.…”

Seroepidemiology of Equine Brucellosis and Role of Horse Carcass Processors in Spread of Brucella Infection in Enugu State, Nigeria

“…The economic importance of equine brucellosis is based on infertility and decrease performance problems caused by the disease. Brucella agents display tropism to gravid uterus, where it invade developing fetuses and associated maternal tissues, resulting in middle or late term abortion, pathognomonic of brucellosis in pregnant animals [19]. Other economically important clinical manifestations of brucellosis in mares include repeat breeder syndrome, increased foaling interval, mastitis, decreased milk yield and birth of weak or unthrifty foals [9].…”

“…The predominance of Brucella antibodies in mares is not surprising because Brucella organisms have predilection for the female reproductive tract, pregnant uterus or fetal tissues; because of the production of erythritol, a 4-carbon sugar in the organs which facilitates the proliferation and growth of the organisms [19]. Additionally, mares are generally kept for longer period in stables than the stallion and this extended period of stay tend to predispose them to Brucella infection.…”

Comparisons of brucellosis between human and veterinary medicine

“…One of the contrasting differences between species is the presence of the carbohydrate erythritol, which plays a significant role in this clinical presentation in animals [57]. Erythritol is produced by placental tissue of species-specific pregnant animals and can be utilized by brucellae as a growth-stimulatory factor and carbon source, and is preferred over glucose [58].…”