Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages

Shivani Sahu, Navin Baid, Deepali Aggarwal, Ankita Sharma, Manisha Gun, Sahanawaz Molla, Anunay Sinha, Ambey Prasad Dwivedi, Amit Tuli, Mahak Sharma, Sanjeev Khosla, Varadharajan Sundaramurthy and Ashwani Kumar ()
Additional contact information
Shivani Sahu: CSIR-Institute of Microbial Technology
Navin Baid: CSIR-Institute of Microbial Technology
Deepali Aggarwal: CSIR-Institute of Microbial Technology
Ankita Sharma: CSIR-Institute of Microbial Technology
Manisha Gun: CSIR-Institute of Microbial Technology
Sahanawaz Molla: Tata Institute of Fundamental Research
Anunay Sinha: CSIR-Institute of Microbial Technology
Ambey Prasad Dwivedi: CSIR-Institute of Microbial Technology
Amit Tuli: CSIR-Institute of Microbial Technology
Mahak Sharma: Indian Institute of Science Education and Research
Sanjeev Khosla: CSIR-Institute of Microbial Technology
Varadharajan Sundaramurthy: Tata Institute of Fundamental Research
Ashwani Kumar: CSIR-Institute of Microbial Technology

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Mycobacterium tuberculosis is a model intracellular pathogen. The spatial-localization of M. tuberculosis inside macrophages is poorly defined. Here, we determine the spatial-localization of M. tuberculosis inside macrophages with reference to the nucleus. Few M. tuberculosis cells are perinuclear, while most are peripheral. Perinuclear M. tuberculosis are transported to lysosomes, have low Adenosine Triphosphate/Adenosine Diphosphate, are non-replicating, and tolerate front-line anti-tubercular medicines. M. tuberculosis pathogenicity determines its spatial location. Virulent M. tuberculosis strains are peripheral. However, avirulent M. tuberculosis strains or attenuated deletion mutants are transported to lysosomes in the perinuclear area. Early Secreted Antigenic Target-6 and Culture Filtrate Protein-10 play a critical role in inhibiting mycobacterial transport to the perinuclear space. Induction of centripetal transport of pathogenic M. tuberculosis-laden cargoes to perinuclear region enhances M. tuberculosis’s delivery to the lysosomes and reduces mycobacterial growth. Interferon-γ directs M. tuberculosis to lysosomes by modulating their perinuclear localization. Interferon-γ upregulates Transmembrane protein 55B and JNK-interacting protein 4 via transcription factor EB. Increased transmembrane protein 55B and JNK-interacting protein 4 levels tether M. tuberculosis-laden cargoes to the dynein motor, causing their perinuclear delivery to lysosomes. These findings shed light on how mycobacterial metabolism, reproduction, and drug susceptibility are connected to virulence-guided spatial localization.

Date: 2025
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-64404-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64404-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-64404-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().