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

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

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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