Targeting type VII/ESX secretion systems for development of novel antimycobacterial drugs.
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.
Daria
D
Bottai
Agnese
A
Serafini
Alessandro
A
Cascioferro
Roland
R
Brosch
Department of Molecular Medicine, University of Padova, Via Gabelli 63 35121, Padova, Italy. riccardo.manganelli@unipd.it.
Riccardo
R
Manganelli
D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D002473:Cell Wall / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D016415:Sequence Alignment; D014774:Virulence
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems