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Depletion of essential mycobacterial gene glmM reduces pathogen survival and induces host-protective immune responses against tuberculosis.
Agarwal, Meetu; Bhaskar, Ashima; Singha, Biplab; Mukhopadhyay, Suparba; Pahuja, Isha; Singh, Archna; Chaturvedi, Shivam; Agarwal, Nisheeth; Dwivedi, Ved Prakash; Nandicoori, Vinay Kumar.
Afiliación
  • Agarwal M; Signal Transduction Laboratory, National Institute of Immunology, New Delhi, India. meetuagarwal2388@gmail.com.
  • Bhaskar A; Department of Molecular Medicine, Jamia Hamdard University, New Delhi, India. meetuagarwal2388@gmail.com.
  • Singha B; Immunobiology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
  • Mukhopadhyay S; Signal Transduction Laboratory, National Institute of Immunology, New Delhi, India.
  • Pahuja I; Immunobiology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
  • Singh A; Immunobiology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
  • Chaturvedi S; CSIR - Institute of Genomics and Integrative Biology, Mall Road, Delhi, India.
  • Agarwal N; Immunobiology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
  • Dwivedi VP; Translational Health Science and Technology Institute (THSTI), Faridabad, India.
  • Nandicoori VK; Immunobiology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Commun Biol ; 7(1): 949, 2024 Aug 06.
Article en En | MEDLINE | ID: mdl-39107377
ABSTRACT
The limitations of TB treatment are the long duration and immune-dampening effects of anti-tuberculosis therapy. The Cell wall plays a crucial role in survival and virulence; hence, enzymes involved in its biosynthesis are good therapeutic targets. Here, we identify Mycobacterium tuberculosis (Mtb) GlmM, (GlmMMtb) engaged in the UDP-GlcNAc synthesis pathway as an essential enzyme. We generated a conditional knockdown strain, Rv-glmMkD using the CRISPR interference-mediated gene silencing approach. Depletion of GlmMMtb affects the morphology and thickness of the cell wall. The Rv-glmMkD strain attenuated Mtb survival in vitro, in the host macrophages (ex vivo), and in a murine mice infection model (in vivo). Results suggest that the depletion of GlmMMtb induces M1 macrophage polarization, prompting a pro-inflammatory cytokine response, apparent from the upregulation of activation markers, including IFNÉ£ and IL-17 that resists the growth of Mtb. These observations provide a rationale for exploring GlmMMtb as a potential therapeutic target.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Tuberculosis / Macrófagos / Mycobacterium tuberculosis Límite: Animals / Female / Humans Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Tuberculosis / Macrófagos / Mycobacterium tuberculosis Límite: Animals / Female / Humans Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido