TARGETING DORMANT BACILLI TO FIGHT TUBERCULOSIS
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which kills about 2 million people annually. Furthermore, 2 billion people worldwide are latently infected with this organism, with 10% of them reactivating to active TB due to re-growth of nonreplicating (dormant...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Mattioli1885
2013-11-01
|
Series: | Mediterranean Journal of Hematology and Infectious Diseases |
Subjects: | |
Online Access: | http://www.mjhid.org/index.php/mjhid/article/view/426 |
_version_ | 1819001431091314688 |
---|---|
author | Lanfranco Fattorini Giovanni Piccaro Alessandro Mustazzolu Federico Giannoni |
author_facet | Lanfranco Fattorini Giovanni Piccaro Alessandro Mustazzolu Federico Giannoni |
author_sort | Lanfranco Fattorini |
collection | DOAJ |
description | Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which kills about 2 million people annually. Furthermore, 2 billion people worldwide are latently infected with this organism, with 10% of them reactivating to active TB due to re-growth of nonreplicating (dormant) Mtb residing in their tissues. Because of the huge reservoir of latent TB it is important to find novel drugs/drug combinations killing dormant bacilli (microaerophiles, anaerobes and drug-tolerant persisters) surviving for decades in a wide spectrum of granulomatous lesions in the lungs of TB patients. Antibiotic treatment of drug-susceptible TB requires administration of isoniazid, rifampin, pyrazinamide, ethambutol for 2 months, followed by isoniazid and rifampin for 4 months. To avoid reactivation of dormant Mtb to active pulmonary TB, up to 9 months of treatment with isoniazid is required. Therefore, a strategy to eliminate dormant bacilli needs to be developed to shorten therapy of active and latent TB and reduce the reservoir of people with latent TB. Finding drugs with high rate of penetration into the caseous granulomas and understanding the biology of dormant bacilli and in particular of persister cells, phenotypically resistant to antibiotics, will be essential to eradicate Mtb from humans. In recent years unprecedented efforts have been done in TB drug discovery, aimed at identifying novel drugs and drug combinations killing both actively replicating and nonreplicating Mtb in vitro, in animal models and in clinical trials in humans. |
first_indexed | 2024-12-20T22:49:06Z |
format | Article |
id | doaj.art-f28e294cb341487ba163bb4721800f6b |
institution | Directory Open Access Journal |
issn | 2035-3006 |
language | English |
last_indexed | 2024-12-20T22:49:06Z |
publishDate | 2013-11-01 |
publisher | Mattioli1885 |
record_format | Article |
series | Mediterranean Journal of Hematology and Infectious Diseases |
spelling | doaj.art-f28e294cb341487ba163bb4721800f6b2022-12-21T19:24:18ZengMattioli1885Mediterranean Journal of Hematology and Infectious Diseases2035-30062013-11-0151e2013072e201307210.4084/mjhid.2013.072318TARGETING DORMANT BACILLI TO FIGHT TUBERCULOSISLanfranco Fattorini0Giovanni PiccaroAlessandro MustazzoluFederico GiannoniLanfranco Fattorini 1Dipartimento di Malattie Infettive, Parassitarie e Immunomediate Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma Tel 06 49903167; E-mail: lanfranco.fattorini@iss.itTuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which kills about 2 million people annually. Furthermore, 2 billion people worldwide are latently infected with this organism, with 10% of them reactivating to active TB due to re-growth of nonreplicating (dormant) Mtb residing in their tissues. Because of the huge reservoir of latent TB it is important to find novel drugs/drug combinations killing dormant bacilli (microaerophiles, anaerobes and drug-tolerant persisters) surviving for decades in a wide spectrum of granulomatous lesions in the lungs of TB patients. Antibiotic treatment of drug-susceptible TB requires administration of isoniazid, rifampin, pyrazinamide, ethambutol for 2 months, followed by isoniazid and rifampin for 4 months. To avoid reactivation of dormant Mtb to active pulmonary TB, up to 9 months of treatment with isoniazid is required. Therefore, a strategy to eliminate dormant bacilli needs to be developed to shorten therapy of active and latent TB and reduce the reservoir of people with latent TB. Finding drugs with high rate of penetration into the caseous granulomas and understanding the biology of dormant bacilli and in particular of persister cells, phenotypically resistant to antibiotics, will be essential to eradicate Mtb from humans. In recent years unprecedented efforts have been done in TB drug discovery, aimed at identifying novel drugs and drug combinations killing both actively replicating and nonreplicating Mtb in vitro, in animal models and in clinical trials in humans.http://www.mjhid.org/index.php/mjhid/article/view/426Tuberculosis, Mycobacterium tuberculois, anti-TB drugs, dormancy. |
spellingShingle | Lanfranco Fattorini Giovanni Piccaro Alessandro Mustazzolu Federico Giannoni TARGETING DORMANT BACILLI TO FIGHT TUBERCULOSIS Mediterranean Journal of Hematology and Infectious Diseases Tuberculosis, Mycobacterium tuberculois, anti-TB drugs, dormancy. |
title | TARGETING DORMANT BACILLI TO FIGHT TUBERCULOSIS |
title_full | TARGETING DORMANT BACILLI TO FIGHT TUBERCULOSIS |
title_fullStr | TARGETING DORMANT BACILLI TO FIGHT TUBERCULOSIS |
title_full_unstemmed | TARGETING DORMANT BACILLI TO FIGHT TUBERCULOSIS |
title_short | TARGETING DORMANT BACILLI TO FIGHT TUBERCULOSIS |
title_sort | targeting dormant bacilli to fight tuberculosis |
topic | Tuberculosis, Mycobacterium tuberculois, anti-TB drugs, dormancy. |
url | http://www.mjhid.org/index.php/mjhid/article/view/426 |
work_keys_str_mv | AT lanfrancofattorini targetingdormantbacillitofighttuberculosis AT giovannipiccaro targetingdormantbacillitofighttuberculosis AT alessandromustazzolu targetingdormantbacillitofighttuberculosis AT federicogiannoni targetingdormantbacillitofighttuberculosis |