The role of ESAT-6 in tuberculosis immunopathology

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 3, 2024

Despite major global efforts to eliminate tuberculosis, which is caused by Mycobacterium tuberculosis (Mtb), this disease remains as a plague of humanity. Several factors associated with the host and Mtb interaction favor infection establishment and/or determine progression. The Early Secreted Antigenic Target 6 kDa (ESAT-6) one most important well-studied mycobacterial virulence factors. This molecule has been described play an role in development tuberculosis-associated pathology subverting crucial components immune responses. review highlights main effector mechanisms ESAT-6 modulates system, directly impacting cell fate

Language: Английский

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Harnessing miRNAs: A Novel Approach to Diagnosis and Treatment of Tuberculosis

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(1)

Published: Jan. 1, 2025

ABSTRACT Mycobacterium tuberculosis ( Mtb ) complex, responsible for (TB) infection, continues to be a predominant global cause of mortality due intricate host‐pathogen interactions that affect disease progression. MicroRNAs (miRNAs), essential posttranscriptional regulators, have become pivotal modulators these relationships. Recent findings indicate miRNAs actively regulate immunological responses complex by modulating autophagy, apoptosis, and immune cell activities. This has resulted in increased interest as prospective diagnostic indicators TB, especially differentiating active infection from latent or inactive stages. Variations miRNA expression during progression offer insights into the response. Furthermore, present potential therapeutic targets host‐directed therapy (HDT) techniques TB infection. work examines function pathogenesis, with objective identifying particular response evaluating their value exploring implications The is enhance comprehension how can facilitate improved diagnosis treatment TB.

Language: Английский

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Advances in Host–Pathogen Interactions in Tuberculosis: Emerging Strategies for Therapeutic Intervention

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1621 - 1621

Published: Feb. 14, 2025

Tuberculosis (TB) remains one of the most challenging infectious diseases, with Mycobacterium tuberculosis (Mtb) employing sophisticated mechanisms to evade host immunity and establish persistent infections. This review explores recent advances in understanding Mtb's immune evasion strategies; granuloma dynamics; emerging immunotherapeutic approaches. Key findings highlight manipulation autophagy; metabolic reprogramming; cytokine pathways by Mtb sustain its survival within cells. Insights into formation reveal critical role bacterial lipids; modulation; hypoxia-driven dormancy maintaining chronic infection. Innovative therapeutic strategies, including host-directed therapies; epigenetic interventions; immunomodulators, hold promise for improving TB management combating drug-resistant strains. Despite these advancements, significant challenges remain, development effective vaccines; addressing latent TB; ensuring equitable access novel treatments. The integration advanced technologies such as artificial intelligence multi-omics approaches, alongside global collaboration, is essential overcome hurdles. underscores importance a multidisciplinary approach tackling TB, ultimate goal eradicating this health threat.

Language: Английский

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Promising Ursolic Acid as a Novel Antituberculosis Agent: Current Progress and Challenges

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 1969 - 1979

Published: May 1, 2024

Abstract: Tuberculosis (TB) stands as the second most prevalent cause of global human mortality from infectious diseases. In 2022, World Health Organization documented an estimated number TB cases reaching 7.5 million, which causes death for 1.13 million patients. The continuous growth drug-resistant due to various mutations in Mycobacterium tuberculosis (MTB) strain, raises urgency exploration novel anti-TB treatments. Ursolic acid (UA) is a natural pentacyclic triterpene found plants that has shown potential agent. This review aims provide overview therapeutic prospects UA against MTB, with particular emphasis on silico, vitro, and vivo studies. Various mechanisms action MTB are briefly recapped silico studies, such enoyl acyl carrier protein reductase inhibitors, FadA5 (Acetyl-CoA acetyltransferase) tuberculosinyl adenosine transferase small heat shock 16.3 inhibitor. overcome drug resistance its synergistic effects existing antituberculosis drugs explained vitro studies using variety methods, Microplate Alamar Blue Assay, Mycobacteria Growth Indicator Tube 960 Resazurin Assays, morphological change evaluation transmission electron microscopy, BALB/C infected multi resistant clinical isolates. Besides promising mechanism drug, complex chemical composition, limited availability supply, lack intellectual property also reviewed those frequently occurring challenges need be addressed successful development Keywords: ursolic acid, tuberculosis, triterpenoid

Language: Английский

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Recent advances in research on Mycobacterium tuberculosis virulence factors and their role in pathogenesis

Journal of Microbiology Immunology and Infection, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Mycobacterium tuberculosis (Mtb) is the causative agent of (TB) in humans and animals. Mtb invades host's lungs via airborne transmission, infecting macrophages causing TB. In some cases, infection can spread to other tissues organs. Despite availability several drugs for TB treatment, emergence multidrug-resistant has led high morbidity mortality rates worldwide. Therefore, it urgent discover new anti-tuberculosis more effective treatment. Recent studies have shown that virulence factors play a crucial role its pathogenicity. By evading immune surveillance through mechanisms such as anti-oxidative stress, nutrient synthesis metabolism, apoptosis host cells, achieve long-term survival host. Understanding pathogenicity will aid development vaccines drugs. this review, we summarize latest research progress on provide reference targeted

Language: Английский

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The danger theory of immunity revisited

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(12), P. 912 - 928

Published: Nov. 7, 2024

Language: Английский

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Five Key Criteria for Identifying Optimal Therapeutic Targets in Protein‐Mediated Diseases

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(4)

Published: Jan. 1, 2025

Abstract Therapeutic trends involve designing ligands to target proteins in various diseases, but no parallel filters have been established prioritize pathological within pathogens for optimal inhibition. This study unveils that order a protein serve as an therapeutic intervention, it must exhibit five key attributes. It should druggable site with recognized cleft which ligand can be fitted high specificity. possess unique structure, distinct sequences having low similarity other non‐targeted proteins. dispensable the pathogenesis of disease, and case microbial infection, crucial survival infectious organisms. available crystallized 3D structure enable high‐throughput screening candidate ligands. occupy accessible localization provide easy route reach its less effort. The justifies rules essential considering ideal any protein‐mediated dysfunction. When these targeting are found protein, eradicating intended ailment primarily enhanced time, money,

Language: Английский

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From Adhesion to Invasion: The Multifaceted Roles of Mycobacterium tuberculosis Lipoproteins

Journal of drug targeting, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 18

Published: Feb. 24, 2025

Tuberculosis (TB) is caused by Mycobacterium tuberculosis, which poses a significant threat to human health . Lipoproteins are predominantly found in the tuberculosis cell wall during infection of invading host. The interacts closely with host direct contact .The genome encodes at least 99 lipoproteins diverse functions, including ABC transport, metabolism, adhesion, invasion, and signal transduction, among others .Different play important roles bacterial survival, cells, vaccine development gene regulation for drug targeting Although only subset these has been functionally investigated, most them require further study This review summarizes progress research related synthesis their involvement functions material immune response, virulence mechanism, development, signaling, enzyme

Language: Английский

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Rv2741 Promotes Mycobacterium Survival by Modulating Macrophage Function via the IL-1α-MAPK Axis

ACS Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

One of the primary healthcare problems in world today is tuberculosis (TB), a chronic infectious illness brought on by Mycobacterium (M. tuberculosis). A distinct family PE_PGRS proteins, encoded M. genome, has attracted more attention because their involvement immune evasion and bacterial pathogenicity. Nevertheless, specific functions mechanisms action for majority proteins remain largely unexplored. This study focuses Rv2741 (PE_PGRS47) gene, which exclusively present pathogenic mycobacteria. To examine function host–pathogen interactions, we created recombinant strains smegmatis smegmatis) that expressed gene. IL-1α was found to be key mediator host response modulation Rv2741. downregulates secretion inhibits MAPK signaling pathway, particularly p38 ERK1/2 pathways, thereby cooperatively inhibiting macrophage autophagy apoptosis. Meanwhile, decrease directly leads changes cytokine pattern reduction nitric oxide (NO) production. multifaceted regulatory mechanism ultimately favors survival macrophages. research significantly expands our understanding function, revealing its crucial role as multifunctional virulence factor tuberculosis.

Language: Английский

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Genetic origins of microbial virulence

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 153 - 177

Published: Jan. 1, 2025

Language: Английский

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