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RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection

Author

Listed:
  • Ramya Sivangala Thandi

    (University of Texas Health Center)

  • Rajesh Kumar Radhakrishnan

    (University of Texas Health Center)

  • Deepak Tripathi

    (University of Texas Health Center)

  • Padmaja Paidipally

    (University of Texas Health Center)

  • Abul K. Azad

    (Texas Biomedical Research Institute)

  • Larry S. Schlesinger

    (Texas Biomedical Research Institute)

  • Buka Samten

    (University of Texas Health Center)

  • Sachin Mulik

    (University of Texas Health Center)

  • Ramakrishna Vankayalapati

    (University of Texas Health Center)

Abstract

Macrophages are professional phagocytes known to play a vital role in controlling Mycobacterium tuberculosis (Mtb) infection and disease progression. Here we compare Mtb growth in mouse alveolar (AMs), peritoneal (PMs), and liver (Kupffer cells; KCs) macrophages and in bone marrow-derived monocytes (BDMs). KCs restrict Mtb growth more efficiently than all other macrophages and monocytes despite equivalent infections through enhanced autophagy. A metabolomics comparison of Mtb-infected macrophages indicates that ornithine and imidazole are two top-scoring metabolites in Mtb-infected KCs and that acetylcholine is the top-scoring in Mtb-infected AMs. Ornithine, imidazole and atropine (acetylcholine inhibitor) inhibit Mtb growth in AMs. Ornithine enhances AMPK mediated autophagy whereas imidazole directly kills Mtb by reducing cytochrome P450 activity. Intranasal delivery of ornithine or imidazole or the two together restricts Mtb growth. Our study demonstrates that the metabolic differences between Mtb-infected AMs and KCs lead to differences in the restriction of Mtb growth.

Suggested Citation

  • Ramya Sivangala Thandi & Rajesh Kumar Radhakrishnan & Deepak Tripathi & Padmaja Paidipally & Abul K. Azad & Larry S. Schlesinger & Buka Samten & Sachin Mulik & Ramakrishna Vankayalapati, 2020. "RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17310-5
    DOI: 10.1038/s41467-020-17310-5
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