AI Article Synopsis
- Mycobacterium tuberculosis can replicate inside macrophages and this study explores its growth in non-phagocytic lung fibroblast cells, focusing on the virulence gene phoP.
- In non-phagocytic fibroblasts, an attenuated M. tuberculosis phoP mutant was able to replicate similarly to virulent strains, unlike in macrophages where phoP plays a critical role.
- The virulent strain caused more damage in human fetal lung fibroblasts compared to attenuated strains, indicating that understanding how M. tuberculosis interacts with different cell types may aid in developing effective vaccines.
Article Abstract
Intracellular pathogen Mycobacterium tuberculosis survives and replicates in macrophages but limited information is available on its replication into non-phagocytic cells. Here we study the role of the M. tuberculosis virulence gene phoP in the intracellular growth with rat and human lung fibroblasts. In contrast to macrophages, attenuated M. tuberculosis phoP mutant was able to multiply intracellularly in fibroblasts at the same level as the virulent M. tuberculosis. However, when M. tuberculosis virulence was studied using human foetal lung fibroblasts, MRC-5 cell line, the virulent strain caused a significant damage in cells compared with attenuated strains BCG and M. tuberculosis phoP mutant. We analysed the effect of cytoskeleton inhibitors in NRK-49F fibroblasts. M. tuberculosis invasion was not inhibited, suggesting that mycobacterial uptake was microtubule and microfilament independent. Our results suggest that PhoP in M. tuberculosis does not regulate intracellular replication in fibroblasts, contrary to what happens in macrophages. The ability of M. tuberculosis phoP mutant to replicate within non-phagocytic cells, such as fibroblasts, without causing damage, could be a potential advantage for a live attenuated vaccine against tuberculosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.micinf.2008.10.013 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Performance of the PhoP (Rv0757/Mb0780) protein as diagnostic antigen for bovine tuberculosis.
Res Vet Sci
December 2024
Instituto Nacional de Tecnología Agropecuaria, Instituto de Agrobiotecnología y Biología Molecular (IB-IABiMo), UEDD INTA-CONICET, Hurlingham, Buenos Aires, Argentina; CONICET, Argentina. Electronic address:
Bovine tuberculosis (bTB), a global zoonotic disease, causes negative effects on human and animal health. PhoP protein is a key regulator of pathogenic phenotypes in members of the Mycobacterium tuberculosis complex, which includes the causative agent of bTB. Despite extensive research on this protein focused in deciphering its regulatory role, little was explored about it as a diagnostic antigen.
View Article and Find Full Text PDFTranscriptional and post-transcriptional regulation of whiB6 by a response regulator PhoP and a small noncoding RNA MTS1338 in Mycobacterium tuberculosis.
Biochem Biophys Res Commun
December 2024
RNA Biology Laboratory, Department of Chemistry, Indian Institute of Technology Delhi, India. Electronic address:
Article Synopsis
- WhiB6 is a gene in pathogenic mycobacteria that is upregulated in response to stress conditions like nitric oxide exposure, low oxygen, and during macrophage infections, primarily controlled by the PhoP regulator.
- The binding of PhoP to specific sequences near the whiB6 gene is crucial for its transcription, and this process is dependent on the phosphorylation of PhoP.
- Additionally, the small RNA molecule MTS1338 stabilizes the whiB6 transcript during stress conditions, enhancing its expression, which helps to improve our understanding of M. tuberculosis regulation mechanisms.
Mycobacterium tuberculosis short mutant H37Rv-S with reduced growth adaptability is more readily recognized by the host immune system.
Microb Pathog
January 2025
State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Beijing Institute of Lifeomics, 102206, Beijing, China. Electronic address:
Mycobacterium tuberculosis (Mtb) is the bacterium responsible for causing Tuberculosis (TB) and understanding its mechanisms of virulence, persistence, and pathogenesis is a global research priority. Attenuated strains of Mtb are valuable tools for investigating the genes and proteins involved in these processes. In this study, we identified an Mtb mutant, H37Rv-S, which exhibits a shorter mycelium, smoother colony, slower growth, and reduced antibiotics resistance compared to the wild-type strain H37Rv.
View Article and Find Full Text PDFMycobacterium bovis mutant in the virulence factors PhoP, ESAT-6 and CFP-10 persisted in mouse organs after a year post-vaccination.
Tuberculosis (Edinb)
December 2024
Instituto de Agrobiotecnología y Biología Molecular, (IABIMO) INTA-CONICET, Argentina; Instituto de Biotecnología, CICVyA, Instituto Nacional de Tecnología Agropecuaria N. Repetto and De los Reseros, Hurlingham, 1686, Buenos Aires, Argentina. Electronic address:
A vaccine for bovine tuberculosis is urgently needed. The BCG vaccine (the Bacille Calmette-Guérin), currently the only licensed vaccine for tuberculosis in humans, offers variable protection in cattle. However, BCG is a highly safe vaccine, and any alternative vaccine must not only offer greater protection than BCG but also match and improve its safety profile.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!