Erythritol Availability in Bovine, Murine and Human Models Highlights a Potential Role for the Host Aldose Reductase during Brucella Infection

Abstract

Erythritol is the preferential carbon source for most brucellae, a group of facultative intracellular bacteria that cause a worldwide zoonosis. Since this polyol is abundant in genital organs of ruminants and swine, it is widely accepted that erythritol accounts at least in part for the characteristic genital tropism of brucellae. Nevertheless, proof of erythritol availability and essentiality during Brucella intracellular multiplication has remained elusive. To investigate this relationship, we compared ΔeryH (erythritol-sensitive and thus predicted to be attenuated if erythritol is present), ΔeryA (erythritol-tolerant but showing reduced growth if erythritol is a crucial nutrient) and wild type B. abortus in various infection models. This reporting system indicated that erythritol was available but not required for B. abortus multiplication in bovine trophoblasts. However, mice and humans have been considered to lack erythritol, and we found that it was available but not required for B. abortus multiplication in human and murine trophoblastic and macrophage-like cells, and in mouse spleen and conceptus (fetus, placenta and envelopes). Using this animal model, we found that B. abortus infected cells and tissues contained aldose reductase, an enzyme that can account for the production of erythritol from pentose cycle precursors.

Infection by Brucella melitensis or Brucella papionis modifies essential physiological functions of human trophoblasts

“…It was argued that Brucella do not infect the human placenta because this organ does not contain erythritol (a carbon source for Brucella whose abundance in ruminant placenta is believed to be the reason for its placental tropism (Smith et al, 1962). However, it was shown that human fetal compartments (Jauniaux, Hempstock, Teng, Battaglia, & Burton, 2005), the fetomaternal blood (Brusati et al, 2005), and trophoblasts (Barbier et al, 2017) do contain erythritol. Moreover, isolation of Brucella from human placenta (Carpenter & Boak, 1931;Georghiou & Young, 1991;Grimaud, 1985;Janbon & Carderas De Kerleau, 1939;Messieri, 1936;Sarram, Feiz, Foruzandeh, & Gazanfarpour, 1974;Zowghi, Hedayeti, Ebadi, & Behroozikhah, 1996) provided unequivocal evidence that this organ is prone to infection.…”

Seroprevalence and risk factors for bovine brucellosis in the Chittagong Metropolitan Area of Bangladesh

“…Sexually mature and pregnant cows are thought to be more susceptible to brucellosis than sexually immature cattle of either sex (Adugna et al., 2013). This pattern might have been attributed to the affinity of this bacterial pathogen to the pregnant uterus, to erythritol in fetal tissue, and possibly to steroid hormones that are higher during pregnancy (Barbier et al., 2017).…”

Mitochondrial fragmentation affects neither the sensitivity to TNFα-induced apoptosis of Brucella-infected cells nor the intracellular replication of the bacteria

“…Indeed, it is known that Brucella is a stealthy bacterium that can replicate massively inside the host cell without impacting its viability. In addition, such highly infected cells can be observed in vivo in different infection models such as alveolar macrophages of intranasally-infected mice 77 or trophoblasts of infected pregnant mice 78 or goats 79 .…”

“…At day 15 PF, mice were anaesthetised with isoflurane and sacrificed by cervical dislocation, as previously described in Barbier et al . 78 . All infections were performed at an Animal Biosafety Level 3 facility.…”