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Targeting Type VII/ESX Secretion Systems for Development of Novel Antimycobacterial Drugs

[ Vol. 20 , Issue. 27 ]

Author(s):

Daria Bottai, Agnese Serafini, Alessandro Cascioferro, Roland Brosch and Riccardo Manganelli   Pages 4346 - 4356 ( 11 )

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.

Affiliation:

Department of Molecular Medicine, University of Padova, Via Gabelli 63 35121, Padova, Italy.



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