Glucose uptake is essential for Brucella abortus growth in the extracellular space of the murine placenta

TL;DR

Brucella abortus needs glucose to grow in the placenta, and a gene called gluP is important for this process, leading to fetal loss in mice.

Contribution

The study identifies glucose as a key nutrient for B. abortus in the placenta and the role of the gluP gene in this process.

Findings

A gluP mutant of B. abortus showed reduced growth in the placenta of pregnant mice.

The gluP mutant caused less inflammation and fetal death compared to the wild type.

Glucose utilization in the placental interstitial space is critical for B. abortus growth.

Abstract

Brucella abortus infects the placenta of its natural bovine host, which results in abortion and transmission of infection to other cattle and to humans. While the metabolism of B. abortus during chronic infection of the mononuclear phagocyte system has been studied, the nutrients fueling growth of B. abortus in the placenta are unknown. We found that in mice, glucose is an important carbon source for B. abortus in the placenta. A gluP mutant lacking a major facilitator superfamily protein required for glucose uptake had diminished growth in the placenta of pregnant mice and caused reduced inflammatory pathology and fetal demise. The gluP mutant was able to replicate intracellularly in a trophoblast cellular model and to cause trophoblast cell death in infected placentas. Attenuated growth of the gluP mutant was maintained in mice conditionally deficient for peroxisome proliferator-activated receptor γ in macrophages, suggesting that M2-like macrophages were not the major site for glucose-dependent growth of B. abortus in the placenta. Our results show that the infected placenta contains multiple distinct nutrient niches and that glucose utilization within the interstitial space of the placenta is an important process contributing to bacterial growth and fetal demise during placental B. abortus infection.

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