Cell state transition analysis identifies interventions that improve control of M. tuberculosis infection by susceptible macrophages

  • bioRxiv. 2023 Feb 10:2023.02.09.527908. doi: 10.1101/2023.02.09.527908.
Shivraj M Yabaji  1 ,  Oleksii S Rukhlenko  2 ,  Sujoy Chatterjee  1 ,  Bidisha Bhattacharya  1 ,  Emily Wood  2 ,  Marina Kasaikina  1 ,  Boris Kholodenko  2  3  4 ,  Alexander A Gimelbrant  5 ,  Igor Kramnik  1  6  7
Affiliations
  • 1. The National Emerging Infectious Diseases Laboratories (NEIDL), Boston University.
  • 2. Systems Biology Ireland, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
  • 3. Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
  • 4. Department of Pharmacology, Yale University School of Medicine, New Haven, USA.
  • 5. Altius Institute for Biomedical Sciences, Seattle, WA, USA.
  • 6. Pulmonary Center, The Department of Medicine, Boston University School of Medicine.
  • 7. Department of Microbiology, Boston University School of Medicine.
PMID: 36798271 DOI: 10.1101/2023.02.09.527908
Abstract

Understanding cell state transitions and purposefully controlling them to improve therapies is a longstanding challenge in biological research and medicine. Here, we identify a transcriptional signature that distinguishes activated macrophages from TB-susceptible and TB-resistant mice. We then apply the cSTAR (cell State Transition Assessment and Regulation) approach to data from screening-by-RNA Sequencing to identify chemical perturbations that shift the. transcriptional state of the TB-susceptible macrophages towards that of TB-resistant cells. Finally, we demonstrate that the compounds identified with this approach enhance resistance of the TB-susceptible mouse macrophages to virulent M. tuberculosis .

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