Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs

Eighty years after the introduction of the first antituberculosis (TB) drug, the treatment of drug-susceptible TB remains very cumbersome, requiring the use of four drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) for two months followed by four months on isoniazid and rifampicin. Two of t...

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Main Author: Catherine Vilchèze
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/10/7/2278
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author Catherine Vilchèze
author_facet Catherine Vilchèze
author_sort Catherine Vilchèze
collection DOAJ
description Eighty years after the introduction of the first antituberculosis (TB) drug, the treatment of drug-susceptible TB remains very cumbersome, requiring the use of four drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) for two months followed by four months on isoniazid and rifampicin. Two of the drugs used in this “short”-course, six-month chemotherapy, isoniazid and ethambutol, target the mycobacterial cell wall. Disruption of the cell wall structure can enhance the entry of other TB drugs, resulting in a more potent chemotherapy. More importantly, inhibition of cell wall components can lead to mycobacterial cell death. The complexity of the mycobacterial cell wall offers numerous opportunities to develop drugs to eradicate <i>Mycobacterium tuberculosis</i>, the causative agent of TB. In the past 20 years, researchers from industrial and academic laboratories have tested new molecules to find the best candidates that will change the face of TB treatment: drugs that will shorten TB treatment and be efficacious against active and latent, as well as drug-resistant TB. Two of these new TB drugs block components of the mycobacterial cell wall and have reached phase 3 clinical trial. This article reviews TB drugs targeting the mycobacterial cell wall in use clinically and those in clinical development.
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spelling doaj.art-73711124fff04055be06ace06b51eed42023-11-16T14:26:25ZengMDPI AGApplied Sciences2076-34172020-03-01107227810.3390/app10072278Mycobacterial Cell Wall: A Source of Successful Targets for Old and New DrugsCatherine Vilchèze0Einstein College of Medicine, 1301 Morris Park Avenue, the Bronx, New York, NY 10461, USAEighty years after the introduction of the first antituberculosis (TB) drug, the treatment of drug-susceptible TB remains very cumbersome, requiring the use of four drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) for two months followed by four months on isoniazid and rifampicin. Two of the drugs used in this “short”-course, six-month chemotherapy, isoniazid and ethambutol, target the mycobacterial cell wall. Disruption of the cell wall structure can enhance the entry of other TB drugs, resulting in a more potent chemotherapy. More importantly, inhibition of cell wall components can lead to mycobacterial cell death. The complexity of the mycobacterial cell wall offers numerous opportunities to develop drugs to eradicate <i>Mycobacterium tuberculosis</i>, the causative agent of TB. In the past 20 years, researchers from industrial and academic laboratories have tested new molecules to find the best candidates that will change the face of TB treatment: drugs that will shorten TB treatment and be efficacious against active and latent, as well as drug-resistant TB. Two of these new TB drugs block components of the mycobacterial cell wall and have reached phase 3 clinical trial. This article reviews TB drugs targeting the mycobacterial cell wall in use clinically and those in clinical development.https://www.mdpi.com/2076-3417/10/7/2278tuberculosisdiscoverymode of actiondrug resistancetoxicitytarget
spellingShingle Catherine Vilchèze
Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs
Applied Sciences
tuberculosis
discovery
mode of action
drug resistance
toxicity
target
title Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs
title_full Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs
title_fullStr Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs
title_full_unstemmed Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs
title_short Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs
title_sort mycobacterial cell wall a source of successful targets for old and new drugs
topic tuberculosis
discovery
mode of action
drug resistance
toxicity
target
url https://www.mdpi.com/2076-3417/10/7/2278
work_keys_str_mv AT catherinevilcheze mycobacterialcellwallasourceofsuccessfultargetsforoldandnewdrugs