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primary topic: Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs

Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs
type: AcademicArticle
type: Article
abstract: The genome of Mycobacterium tuberculosis encodes for a large repertoire of toxin-antitoxin systems. In the present study, MenT3 and MenT4 toxins belonging to MenAT subfamily of TA systems have been functionally characterized. We demonstrate that ectopic expression of these toxins inhibits bacterial growth and this is rescued upon co-expression of their cognate antitoxins. Here, we show that simultaneous deletion of menT3 and menT4 results in enhanced susceptibility of M. tuberculosis upon exposure to oxidative stress and attenuated growth in guinea pigs and mice. We observed reduced expression of transcripts encoding for proteins that are essential or required for intracellular growth in mid-log phase cultures of ΔmenT4ΔT3 compared to parental strain. Further, the transcript levels of proteins involved in efficient bacterial clearance were increased in lung tissues of ΔmenT4ΔT3 infected mice relative to parental strain infected mice. We show that immunization of mice and guinea pigs with ΔmenT4ΔT3 confers significant protection against M. tuberculosis infection. Remarkably, immunization of mice with ΔmenT4ΔT3 results in increased antigen-specific TH1 bias and activated memory T cell response. We conclude that MenT3 and MenT4 are important for M. tuberculosis pathogenicity and strains lacking menT3 and menT4 have the potential to be explored further as vaccine candidates.
date: 2024-06
volume: 15
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

Amit Awasthi
type: Person
given name: Amit
family name: Awasthi

Zaigham Abbas Rizvi
type: Person
given name: Zaigham Abbas
family name: Rizvi

Ramandeep Singh
type: Person
given name: Ramandeep
family name: Singh

Saurabh Chugh
type: Person
given name: Saurabh
family name: Chugh

Krishan Gopal Thakur
type: Person
given name: Krishan Gopal
family name: Thakur

Saqib Kidwai
type: Person
given name: Saqib
family name: Kidwai

Tannu Priya Gosain
type: Person
given name: Tannu Priya
family name: Gosain

Neeraj Kumar Chauhan
type: Person
given name: Neeraj Kumar
family name: Chauhan

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primary topic: Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs