title: Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages
creator: Sahu, Shivani
creator: Baid, Navin
creator: Aggarwal, Deepali
creator: Sharma, Ankita
creator: Gun, Manisha
creator: Molla, Sahanawaz
creator: Sinha, Anunay
creator: Dwivedi, Ambey Prasad
creator: Tuli, Amit
creator: Sharma, Mahak
creator: Khosla, Sanjeev
creator: Sundaramurthy, Varadharajan
creator: Kumar, Ashwani
description: 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.
publisher: Springer Science and Business Media LLC
date: 2025-10
type: Article
type: NonPeerReviewed
identifier:   Sahu, Shivani and Baid, Navin and Aggarwal, Deepali and Sharma, Ankita and Gun, Manisha and Molla, Sahanawaz and Sinha, Anunay and Dwivedi, Ambey Prasad and Tuli, Amit and Sharma, Mahak and Khosla, Sanjeev and Sundaramurthy, Varadharajan and Kumar, Ashwani  (2025) Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages.  Nat. Commun., 16 (1).  p. 9368.      
relation: http://crdd.osdd.net/open/3266/