Related Experiment Video

Updated: May 25, 2026

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
09:57

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

Published on: April 5, 2017

Antigen 85C inhibition restricts Mycobacterium tuberculosis growth through disruption of cord factor biosynthesis

Thulasi Warrier1, Marielle Tropis, Jim Werngren

  • 1Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.

Antimicrobial Agents and Chemotherapy
|February 1, 2012
PubMed

Insights

A novel inhibitor, I3-AG85, targets Antigen 85C (Ag85C) in Mycobacterium tuberculosis, blocking essential trehalose dimycolate (TDM) synthesis and disrupting cell envelope integrity. This shows promise for new antimycobacterial drugs against resistant strains.

Area of Science:

  • Microbiology
  • Biochemistry
  • Drug Discovery

Background:

  • The Antigen 85 (Ag85) protein family (Ag85A, -B, -C) is crucial for Mycobacterium tuberculosis cell envelope biogenesis.
  • Ag85 proteins synthesize trehalose dimycolate (TDM), essential for virulence, and link mycolic acids to cell wall components.

Purpose of the Study:

  • To characterize a novel inhibitor, I3-AG85, targeting Ag85C.
  • To investigate the effect of I3-AG85 on M. tuberculosis growth, survival, and mycolic acid synthesis.

Main Methods:

  • Isolation and testing of novel Ag85C inhibitors.
  • Broth culture and macrophage infection models for M. tuberculosis.
  • Minimum Inhibitory Concentration (MIC) determination against drug-susceptible and resistant strains.
  • Nuclear Magnetic Resonance (NMR) for inhibitor binding analysis.
  • Quantification of mycolic acid-linked lipids and envelope integrity assessment.

Main Results:

  • I3-AG85 demonstrated dose-dependent inhibition of M. tuberculosis division and survival in macrophages.
  • Identical MICs were observed for drug-susceptible and extensively drug-resistant/multidrug-resistant M. tuberculosis strains.
  • NMR confirmed I3-AG85 binding to Ag85C.
  • Specific blockade of TDM synthesis with trehalose monomycolate accumulation was observed.
  • Envelope integrity disruption and inhibition in an Ag85C-deficient strain confirmed Ag85C as the target.

Conclusions:

  • Ag85 proteins, particularly Ag85C, are validated as promising targets for novel antimycobacterial drug development.
  • I3-AG85 represents a potential lead compound for new anti-TB therapies effective against drug-resistant tuberculosis.
  • Targeting mycolic acid synthesis via Ag85 inhibition offers a viable strategy to combat M. tuberculosis.

More Related Videos

An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis09:34

An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis

Published on: August 16, 2021

Preparation of Mycobacterium tuberculosis Culture Filtrate to Understand TB Pathogenesis07:32

Preparation of Mycobacterium tuberculosis Culture Filtrate to Understand TB Pathogenesis

Published on: March 28, 2025

Related Concept Videos

Pulmonary Tuberculosis II01:28

Pulmonary Tuberculosis II

Tuberculosis, or TB, is a bacterial infectious disease caused by Mycobacterium tuberculosis. While its primary impact is on the lungs, leading to pulmonary tuberculosis, it can also affect various other organs, a condition referred to as extrapulmonary tuberculosis.
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
Pulmonary Tuberculosis IV01:26

Pulmonary Tuberculosis IV

Tuberculosis, more commonly referred to as TB, is an infectious disease stemming from Mycobacterium tuberculosis. While it primarily impacts the lungs, TB can also affect other body areas. Given its severity and global impact, timely and accurate diagnosis is crucial for controlling its spread and improving patient outcomes.
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...
Pulmonary Tuberculosis I01:29

Pulmonary Tuberculosis I

Tuberculosis, often called TB, is a contagious illness primarily caused by Mycobacterium tuberculosis. It mainly affects the lung parenchyma but can also impact other body parts.
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...