Chapter 28 : ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins

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The different bacterial species within the tree of life ( ) possess a range of secretion systems, which play important roles in the transport of proteins across the various types of bacterial cell envelopes. Classically, Gram staining was used for differentiating Gram-positive and Gram-negative bacteria, but classifications on cell envelope architecture might come closer to the biological reality, and thus, bacteria may also be differentiated according to their cell envelopes into diderm-lipopolysaccharide (archetypal Gram-negative), monoderm (archetypal Gram-positive), and diderm-mycolate (archetypal acid-fast) bacteria ( ). For Gram-negative bacteria a range of at least eight different secretion systems has been described (types I to VI, VIII, and IX) ( ). While in monoderm bacteria secretion and export are synonymous, in diderm bacteria the secretion is completed only upon translocation of the substrates across the outer membrane ( ). The here-reviewed mycobacterial ESAT-6 secretion (ESX) systems ( ), which were also named type VII secretion (T7S) systems ( ), represent a particular class of protein export and/or secretion systems, for which at present only the inner-membrane translocation machinery has been explored in more detail ( ), whereas it remains unknown how ESX/T7S-exported proteins get transported through the mycobacterial outer membrane into the extracellular environment ( ). Indeed, one of the remarkable characteristics of mycobacteria is their complex cell envelope, which is shared to some extent with other members of the , a suborder of the phylum ( ). Mycobacteria are surrounded by a diderm cell envelope, consisting of an inner membrane, a peptidoglycan layer, an arabinogalactan layer, an outer membrane, named mycomembrane, which is composed of covalently linked mycolic acids and extractable lipids, and a capsule ( ). This unusual cell envelope requires complex secretion systems for the export/secretion of proteins, such as those of the SecA and twin-arginine translocation pathways, as well as the specialized ESX/T7S systems ( ), which were first discovered almost 20 years ago during analyses of the genome sequence and the proteome of H37Rv ( ). Moreover, T7S-like systems that share some core components of mycobacterial ESX/T7S systems exist in various genera of the phylum , representing many classical Gram-positive bacterial species ( ), which, however, are not the subject of the current review.

Citation: Vaziri F, Brosch R. 2019. ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins, p 351-362. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PSIB-0029-2019
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Image of Figure 1
Figure 1

Genetic organization of the ESX loci. Shown is a schematic representation of the approximative genomic sites of the ESX-1 to ESX-5 clusters in the H37Rv genome. Gene nomenclature and gene color scheme were adapted from reference .

Citation: Vaziri F, Brosch R. 2019. ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins, p 351-362. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PSIB-0029-2019
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Image of Figure 2
Figure 2

Representation of top and side views of the ESX/T7S system based on recent structural data generated by cryo-electron microscopy and single-particle analysis on an ESX-5 system from , in comparison to selected examples of secretion systems from Gram-negative bacteria. The positions of the inner membrane (IM), outer membrane (OM), and mycomembrane (MM) are indicated. Adapted from reference , with permission.

Citation: Vaziri F, Brosch R. 2019. ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins, p 351-362. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PSIB-0029-2019
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Figure 3

Interplay of ESX-1 and ESX-3 in host-pathogen interactions. ESX-1 is essential for the bacterial phagosome-to-cytosol transition by involving a cGAS/STING/TBK1/IRF-3/type I interferon signalling axis and AIM2 and NLRP3 inflammasome activities. In an ESX-1-dependent manner, the ESCRT machinery is recruited to phagosomes, while ESX-3 effectors (EsxG-EsxH) antagonize the host damage response by blocking the recruitment of HRS, ESCRT-III, and GAL3. The scheme is adapted from reference , with some additions from reference , with permission.

Citation: Vaziri F, Brosch R. 2019. ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins, p 351-362. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PSIB-0029-2019
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