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.

Highlights

  • To survive and multiply any pathogen must harvest nutrients and adapt to the carbon, energy and nitrogen sources that are available in the host

  • We set up and validated a reporting system to detect the presence and catabolism of erythritol in the Brucella replicative niche, and this system demonstrated the availability of this polyol in infection models of bovine, human and murine origin, extending previous research in macrophages and mice (Burkhardt et al, 2005) to trophoblastic cell lines

  • Because erythritol is present in comparatively large amounts in the placenta and genital tissues of ruminants and swine and because Brucella is found inside trophoblastic cells of ruminants and uses erythritol very efficiently, it has been widely assumed that trophoblasts produce erythritol

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Summary

Introduction

To survive and multiply any pathogen must harvest nutrients and adapt to the carbon, energy and nitrogen sources that are available in the host. Massive intratrophoblastic colonization occurs in brucellosis by B. abortus in cows, B. melitensis in goats and sheep, B. ovis in sheep, B. suis in sows and B. canis in bitches (reviewed in Anderson et al, 1986b), and the infection of trophoblasts is a key step in the loss of integrity of the placenta that leads to abortion (Samartino and Enright, 1993) and subsequent dissemination These events are critical in the biology of Brucella as these bacteria do not survive long in the environment and are transmitted mostly by contact with aborted tissues and fluids as well as venereally and congenitally (Moreno and Moriyón, 2006). Not detected in early studies, more recent literature from endemic areas report a correlation between adverse pregnancy outcomes and Brucella infection (Khan et al, 2001; Karcaaltincaba et al, 2010; Al-Tawfiq and Memish, 2013; Vilchez et al, 2015), and epididymo-orchitis occurs in up to 20% of infected males (Navarro-Martinez et al, 2001)

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