Abstract
The emergence of multi- and extensively-drug resistant strains of Mycobacterium tuberculosis makes the development of novel anti-tubercular compounds and the identification of alternative mycobacterial drugable targets urgent priorities. Recently, type VII secretion systems (T7SS) have been discovered in mycobacteria. The genome of M. tuberculosis encodes 5 of such systems (ESX-1 to - 5), three of which have been characterized and shown to be essential for viability (ESX-3, ESX-5) or virulence (ESX-1, ESX-5). Because of their crucial role in host-pathogen interactions as well as their involvement in basic biological processes of tubercle bacilli, T7SS/ESX represent promising targets for novel anti-tuberculosis drugs. Here, we review the current knowledge of the T7SS/ESX and their impact on M. tuberculosis physiology and virulence. Finally, we discuss the possible approaches to develop T7SS/ESX inhibitors.
Keywords: M. tuberculosis, secretion, virulence, drugs development, tuberculosis.
Current Pharmaceutical Design
Title:Targeting Type VII/ESX Secretion Systems for Development of Novel Antimycobacterial Drugs
Volume: 20 Issue: 27
Author(s): Daria Bottai, Agnese Serafini, Alessandro Cascioferro, Roland Brosch and Riccardo Manganelli
Affiliation:
Keywords: M. tuberculosis, secretion, virulence, drugs development, tuberculosis.
Abstract: The emergence of multi- and extensively-drug resistant strains of Mycobacterium tuberculosis makes the development of novel anti-tubercular compounds and the identification of alternative mycobacterial drugable targets urgent priorities. Recently, type VII secretion systems (T7SS) have been discovered in mycobacteria. The genome of M. tuberculosis encodes 5 of such systems (ESX-1 to - 5), three of which have been characterized and shown to be essential for viability (ESX-3, ESX-5) or virulence (ESX-1, ESX-5). Because of their crucial role in host-pathogen interactions as well as their involvement in basic biological processes of tubercle bacilli, T7SS/ESX represent promising targets for novel anti-tuberculosis drugs. Here, we review the current knowledge of the T7SS/ESX and their impact on M. tuberculosis physiology and virulence. Finally, we discuss the possible approaches to develop T7SS/ESX inhibitors.
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Bottai Daria, Serafini Agnese, Cascioferro Alessandro, Brosch Roland and Manganelli Riccardo, Targeting Type VII/ESX Secretion Systems for Development of Novel Antimycobacterial Drugs, Current Pharmaceutical Design 2014; 20 (27) . https://dx.doi.org/10.2174/1381612819666131118170717
DOI https://dx.doi.org/10.2174/1381612819666131118170717 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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