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Publication : PPARγ-mediated increase in glucose availability sustains chronic Brucella abortus infection in alternatively activated macrophages.

First Author  Xavier MN Year  2013
Journal  Cell Host Microbe Volume  14
Issue  2 Pages  159-70
PubMed ID  23954155 Mgi Jnum  J:317631
Mgi Id  MGI:6855113 Doi  10.1016/j.chom.2013.07.009
Citation  Xavier MN, et al. (2013) PPARgamma-mediated increase in glucose availability sustains chronic Brucella abortus infection in alternatively activated macrophages. Cell Host Microbe 14(2):159-70
abstractText  Eradication of persistent intracellular bacterial pathogens with antibiotic therapy is often slow or incomplete. However, strategies to augment antibiotics are hampered by our poor understanding of the nutritional environment that sustains chronic infection. Here we show that the intracellular pathogen Brucella abortus survives and replicates preferentially in alternatively activated macrophages (AAMs), which are more abundant during chronic infection. A metabolic shift induced by peroxisome proliferator-activated receptor gamma (PPARgamma), which increases intracellular glucose availability, is identified as a causal mechanism promoting enhanced bacterial survival in AAMs. Glucose uptake was crucial for increased replication of B. abortus in AAMs, and for chronic infection, as inactivation of the bacterial glucose transporter gluP reduced both intracellular survival in AAMs and persistence in mice. Thus, a shift in intracellular nutrient availability induced by PPARgamma promotes chronic persistence of B. abortus within AAMs, and targeting this pathway may aid in eradicating chronic infection.
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