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Pulmonary Tuberculosis V01:28

Pulmonary Tuberculosis V

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Medical management of tuberculosis (TB) patients involves a comprehensive approach that includes diagnosis, treatment, and monitoring. The specific strategies can vary depending on the type of tuberculosis (latent or active), the patient's overall health status, and other considerations.
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
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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.
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The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
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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.
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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.
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System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
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Inhibiting Mycobacterium tuberculosis within and without.

Stewart T Cole1

  • 1Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland stewart.cole@epfl.ch.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
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Drug-resistant tuberculosis demands new treatments. Phenotypic screening identified new drugs, but cell-based screens offer better disease mimicry for future tuberculosis drug development.

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antibioticsdrug discoverydrug resistancephagocytestuberculosis

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Area of Science:

  • Microbiology
  • Drug Discovery
  • Infectious Diseases

Background:

  • Tuberculosis (TB) is a global health threat with increasing drug resistance.
  • Limited treatment options necessitate novel drug development targeting Mycobacterium tuberculosis.
  • Past efforts included drug repurposing and target-based screening with limited success.

Purpose of the Study:

  • To review scientific progress and the pipeline for new tuberculosis drugs.
  • To highlight advancements in screening methodologies for TB drug discovery.
  • To discuss challenges and limitations in current TB drug development.

Main Methods:

  • Phenotypic screening against live Mycobacterium tuberculosis.
  • Target-based screening approaches.
  • Cell-based screening assays, particularly in macrophages, to mimic the disease state.
  • Investigating novel targets like the ESX-1 secretion system, electron transport chain, and cholesterol metabolism.

Main Results:

  • Phenotypic screening yielded promising drugs like bedaquiline, pretomanid, and delamanid.
  • Cell-based screens identified targets crucial for intracellular survival and virulence, not just in vitro growth.
  • These screens revealed the druggability of energy metabolism and cholesterol pathways in M. tuberculosis.

Conclusions:

  • Cell-based screening represents a more accurate approach for identifying TB drug leads.
  • Despite progress, significant challenges remain due to lack of industrial commitment and socio-economic factors.
  • Continued innovation in screening and target identification is crucial for combating drug-resistant tuberculosis.