PPARγ-mediated increase in glucose availability sustains chronic brucella abortus infection in alternatively activated macrophages

Mariana N. Xavier, Maria G. Winter, Alanna M. Spees, Andreas B. Den Hartigh, Kim Nguyen, Christelle M. Roux, Teane M A Silva, Vidya L. Atluri, Tobias Kerrinnes, A. Marijke Keestra, Denise M. Monack, Paul A Luciw, Richard A. Eigenheer, Andreas J Baumler, Renato L. Santos, Renee M Tsolis

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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 γ (PPARγ), 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 PPARγ promotes chronic persistence of B. abortus within AAMs, and targeting this pathway may aid in eradicating chronic infection.

Original languageEnglish (US)
Pages (from-to)159-170
Number of pages12
JournalCell Host and Microbe
Volume14
Issue number2
DOIs
StatePublished - Aug 14 2013

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Brucella abortus
Peroxisome Proliferator-Activated Receptors
Macrophages
Glucose
Infection
Anti-Bacterial Agents
Facilitative Glucose Transport Proteins
Food

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

PPARγ-mediated increase in glucose availability sustains chronic brucella abortus infection in alternatively activated macrophages. / Xavier, Mariana N.; Winter, Maria G.; Spees, Alanna M.; Den Hartigh, Andreas B.; Nguyen, Kim; Roux, Christelle M.; Silva, Teane M A; Atluri, Vidya L.; Kerrinnes, Tobias; Keestra, A. Marijke; Monack, Denise M.; Luciw, Paul A; Eigenheer, Richard A.; Baumler, Andreas J; Santos, Renato L.; Tsolis, Renee M.

In: Cell Host and Microbe, Vol. 14, No. 2, 14.08.2013, p. 159-170.

Research output: Contribution to journalArticle

Xavier, MN, Winter, MG, Spees, AM, Den Hartigh, AB, Nguyen, K, Roux, CM, Silva, TMA, Atluri, VL, Kerrinnes, T, Keestra, AM, Monack, DM, Luciw, PA, Eigenheer, RA, Baumler, AJ, Santos, RL & Tsolis, RM 2013, 'PPARγ-mediated increase in glucose availability sustains chronic brucella abortus infection in alternatively activated macrophages', Cell Host and Microbe, vol. 14, no. 2, pp. 159-170. https://doi.org/10.1016/j.chom.2013.07.009
Xavier, Mariana N. ; Winter, Maria G. ; Spees, Alanna M. ; Den Hartigh, Andreas B. ; Nguyen, Kim ; Roux, Christelle M. ; Silva, Teane M A ; Atluri, Vidya L. ; Kerrinnes, Tobias ; Keestra, A. Marijke ; Monack, Denise M. ; Luciw, Paul A ; Eigenheer, Richard A. ; Baumler, Andreas J ; Santos, Renato L. ; Tsolis, Renee M. / PPARγ-mediated increase in glucose availability sustains chronic brucella abortus infection in alternatively activated macrophages. In: Cell Host and Microbe. 2013 ; Vol. 14, No. 2. pp. 159-170.
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