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primary topic: Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages

Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages
type: AcademicArticle
type: Article
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: 2025-10
volume: 16
issue: 1
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

Springer Science and Business Media LLC
type: Organization

Nat. Commun.
type: Collection

Ashwani Kumar
type: Person
given name: Ashwani
family name: Kumar

Mahak Sharma
type: Person
given name: Mahak
family name: Sharma

Ambey Prasad Dwivedi
type: Person
given name: Ambey Prasad
family name: Dwivedi

Amit Tuli
type: Person
given name: Amit
family name: Tuli

Shivani Sahu
type: Person
given name: Shivani
family name: Sahu

Ankita Sharma
type: Person
given name: Ankita
family name: Sharma

Navin Baid
type: Person
given name: Navin
family name: Baid

Manisha Gun
type: Person
given name: Manisha
family name: Gun

Sahanawaz Molla
type: Person
given name: Sahanawaz
family name: Molla

Sanjeev Khosla
type: Person
given name: Sanjeev
family name: Khosla

Varadharajan Sundaramurthy
type: Person
given name: Varadharajan
family name: Sundaramurthy

Anunay Sinha
type: Person
given name: Anunay
family name: Sinha

Deepali Aggarwal
type: Person
given name: Deepali
family name: Aggarwal

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primary topic: Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages