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Expression of a unique M. tuberculosis DNA MTase Rv1509 in M. smegmatis alters the gene expression pattern and enhances virulence.
Manjunath, P; Ahmad, Javeed; Samal, Jasmine; Rani, Anshu; Sheikh, Javaid Ahmad; Zarin, Sheeba; Ahuja, Yashika; Alam, Anwar; Hasnain, Seyed E; Ehtesham, Nasreen Z.
Afiliación
  • Manjunath P; Inflammation Biology and Cell Signaling Laboratory, National Institute of Pathology, New Delhi, India.
  • Ahmad J; Department of Biotechnology, Jamia Hamdard, New Delhi, India.
  • Samal J; Molecular Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
  • Rani A; Inflammation Biology and Cell Signaling Laboratory, National Institute of Pathology, New Delhi, India.
  • Sheikh JA; Kusuma School of Biological Sciences, Indian Institute of Technology, New Delhi, India.
  • Zarin S; Department of Biotechnology, Jamia Hamdard, New Delhi, India.
  • Ahuja Y; Department of Biotechnology, Jamia Hamdard, New Delhi, India.
  • Alam A; Department of Life Science, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India.
  • Hasnain SE; Department of Life Science, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India.
  • Ehtesham NZ; Department of Biotechnology, Sharda School of Engineering Sciences and Technology, Sharda University, Greater Noida, Uttar Pradesh, India.
Front Microbiol ; 15: 1344857, 2024.
Article en En | MEDLINE | ID: mdl-38803374
ABSTRACT
Mycobacterium tuberculosis (M. tb) genome encompasses 4,173 genes, about a quarter of which remain uncharacterized and hypothetical. Considering the current limitations associated with the diagnosis and treatment of tuberculosis, it is imperative to comprehend the pathomechanism of the disease and host-pathogen interactions to identify new drug targets for intervention strategies. Using in-silico comparative genome analysis, we identified one of the M. tb genes, Rv1509, as a signature protein exclusively present in M. tb. To explore the role of Rv1509, a likely methyl transferase, we constructed a knock-in Mycobacterium smegmatis (M. smegmatis) constitutively expressing Rv1509 (Ms_Rv1509). The Ms_Rv1509 led to differential expression of many transcriptional regulator genes as assessed by RNA-seq analysis. Further, in-vitro and in-vivo studies demonstrated an enhanced survival of Ms_Rv1509 inside the host macrophages. Ms_Rv1509 also promoted phagolysosomal escape inside macrophages to boost bacterial replication and dissemination. In-vivo infection studies revealed that Ms_Rv1509 survives better than BCG and causes pathological manifestations in the pancreas after intraperitoneal infection. Long-time survival of Ms_Rv1509 resulted in lymphocyte migration, increased T regulatory cells, giant cell formation, and likely granuloma formation in the pancreas, pointing toward the role of Rv1509 in M. tb pathogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Microbiol Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Microbiol Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Suiza