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

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Abstract:

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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Figures

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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References

/content/book/10.1128/9781683670285.chap28
1. Hug LA,, Baker BJ,, Anantharaman K,, Brown CT,, Probst AJ,, Castelle CJ,, Butterfield CN,, Hernsdorf AW,, Amano Y,, Ise K,, Suzuki Y,, Dudek N,, Relman DA,, Finstad KM,, Amundson R,, Thomas BC,, Banfield JF . 2016. A new view of the tree of life. Nat Microbiol 1 : 16048.[CrossRef][PubMed]
2. Chagnot C,, Zorgani MA,, Astruc T,, Desvaux M . 2013. Proteinaceous determinants of surface colonization in bacteria: bacterial adhesion and biofilm formation from a protein secretion perspective. Front Microbiol 4 : 303.[CrossRef][PubMed]
3. Gerlach RG,, Hensel M . 2007. Protein secretion systems and adhesins: the molecular armory of Gram-negative pathogens. Int J Med Microbiol 297 : 401 415.[CrossRef][PubMed]
4. Green ER,, Mecsas J . 2016. Bacterial secretion systems: an overview. Microbiol Spectr 4 : VMBF-0012-2015.[CrossRef]
5. Veith PD,, Glew MD,, Gorasia DG,, Reynolds EC . 2017. Type IX secretion: the generation of bacterial cell surface coatings involved in virulence, gliding motility and the degradation of complex biopolymers. Mol Microbiol 106 : 35 53.[CrossRef][PubMed]
6. Sørensen AL,, Nagai S,, Houen G,, Andersen P,, Andersen AB . 1995. Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis. Infect Immun 63 : 1710 1717.
7. Brodin P,, Rosenkrands I,, Andersen P,, Cole ST,, Brosch R . 2004. ESAT-6 proteins: protective antigens and virulence factors? Trends Microbiol 12 : 500 508.[CrossRef][PubMed]
8. Abdallah AM,, Gey van Pittius NC,, Champion PA,, Cox J,, Luirink J,, Vandenbroucke-Grauls CM,, Appelmelk BJ,, Bitter W . 2007. Type VII secretion—mycobacteria show the way. Nat Rev Microbiol 5 : 883 891.[CrossRef][PubMed]
9. Houben EN,, Bestebroer J,, Ummels R,, Wilson L,, Piersma SR,, Jiménez CR,, Ottenhoff TH,, Luirink J,, Bitter W . 2012. Composition of the type VII secretion system membrane complex. Mol Microbiol 86 : 472 484.[CrossRef][PubMed]
10. Beckham KS,, Ciccarelli L,, Bunduc CM,, Mertens HD,, Ummels R,, Lugmayr W,, Mayr J,, Rettel M,, Savitski MM,, Svergun DI,, Bitter W,, Wilmanns M,, Marlovits TC,, Parret AH,, Houben EN . 2017. Structure of the mycobacterial ESX-5 type VII secretion system membrane complex by single-particle analysis. Nat Microbiol 2 : 17047.[CrossRef][PubMed]
11. Gröschel MI,, Sayes F,, Simeone R,, Majlessi L,, Brosch R . 2016. ESX secretion systems: mycobacterial evolution to counter host immunity. Nat Rev Microbiol 14 : 677 691.[CrossRef][PubMed]
12. Zuber B,, Chami M,, Houssin C,, Dubochet J,, Griffiths G,, Daffé M . 2008. Direct visualization of the outer membrane of mycobacteria and corynebacteria in their native state. J Bacteriol 190 : 5672 5680.[CrossRef][PubMed]
13. Kaur D,, Guerin ME,, Skovierová H,, Brennan PJ,, Jackson M . 2009. Chapter 2: biogenesis of the cell wall and other glycoconjugates of Mycobacterium tuberculosis. Adv Appl Microbiol 69 : 23 78.[CrossRef]
14. Daffé M . 2015. The cell envelope of tubercle bacilli. Tuberculosis (Edinb) 95( Suppl 1) : S155 S158.[CrossRef][PubMed]
15. Touchette MH,, Seeliger JC . 2017. Transport of outer membrane lipids in mycobacteria. Biochim Biophys Acta Mol Cell Biol Lipids 1862 : 1340 1354.[CrossRef][PubMed]
16. Bitter W,, Houben EN,, Bottai D,, Brodin P,, Brown EJ,, Cox JS,, Derbyshire K,, Fortune SM,, Gao LY,, Liu J,, Gey van Pittius NC,, Pym AS,, Rubin EJ,, Sherman DR,, Cole ST,, Brosch R . 2009. Systematic genetic nomenclature for type VII secretion systems. PLoS Pathog 5 : e1000507.[CrossRef][PubMed]
17. Cole ST,, Brosch R,, Parkhill J,, Garnier T,, Churcher C,, Harris D,, Gordon SV,, Eiglmeier K,, Gas S,, Barry CE III,, Tekaia F,, Badcock K,, Basham D,, Brown D,, Chillingworth T,, Connor R,, Davies R,, Devlin K,, Feltwell T,, Gentles S,, Hamlin N,, Holroyd S,, Hornsby T,, Jagels K,, Krogh A,, McLean J,, Moule S,, Murphy L,, Oliver K,, Osborne J,, Quail MA,, Rajandream MA,, Rogers J,, Rutter S,, Seeger K,, Skelton J,, Squares R,, Squares S,, Sulston JE,, Taylor K,, Whitehead S,, Barrell BG . 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393 : 537 544.[CrossRef][PubMed]
18. Tekaia F,, Gordon SV,, Garnier T,, Brosch R,, Barrell BG,, Cole ST . 1999. Analysis of the proteome of Mycobacterium tuberculosis in silico. Tuber Lung Dis 79 : 329 342.[CrossRef][PubMed]
19. Unnikrishnan M,, Constantinidou C,, Palmer T,, Pallen MJ . 2017. The enigmatic Esx proteins: looking beyond mycobacteria. Trends Microbiol 25 : 192 204.[CrossRef][PubMed]
20. Pallen MJ . 2002. The ESAT-6/WXG100 superfamily—and a new Gram-positive secretion system? Trends Microbiol 10 : 209 212.[CrossRef]
21. Dumas E,, Christina Boritsch E,, Vandenbogaert M,, Rodríguez de la Vega RC,, Thiberge JM,, Caro V,, Gaillard JL,, Heym B,, Girard-Misguich F,, Brosch R,, Sapriel G . 2016. Mycobacterial pan-genome analysis suggests important role of plasmids in the radiation of type VII secretion systems. Genome Biol Evol 8 : 387 402.[CrossRef][PubMed]
22. Newton-Foot M,, Warren RM,, Sampson SL,, van Helden PD,, Gey van Pittius NC . 2016. The plasmid-mediated evolution of the mycobacterial ESX (type VII) secretion systems. BMC Evol Biol 16 : 62.[CrossRef][PubMed]
23. Ummels R,, Abdallah AM,, Kuiper V,, Aâjoud A,, Sparrius M,, Naeem R,, Spaink HP,, van Soolingen D,, Pain A,, Bitter W . 2014. Identification of a novel conjugative plasmid in mycobacteria that requires both type IV and type VII secretion. mBio 5 : e01744-14.[CrossRef][PubMed]
24. Stoop EJ,, Bitter W,, van der Sar AM . 2012. Tubercle bacilli rely on a type VII army for pathogenicity. Trends Microbiol 20 : 477 484.[CrossRef][PubMed]
25. Queval CJ,, Brosch R,, Simeone R . 2017. The macrophage: a disputed fortress in the battle against Mycobacterium tuberculosis. Front Microbiol 8 : 2284.[CrossRef][PubMed]
26. Majlessi L,, Prados-Rosales R,, Casadevall A,, Brosch R . 2015. Release of mycobacterial antigens. Immunol Rev 264 : 25 45.[CrossRef][PubMed]
27. Ates LS,, Houben EN,, Bitter W . 2016. Type VII secretion: a highly versatile secretion system. Microbiol Spectr 4 : VMBF-0011-2015.[CrossRef]
28. Madacki J,, Mas Fiol G,, Brosch R . 2019. Update on the virulence factors of the obligate pathogen Mycobacterium tuberculosis and related tuberculosis-causing mycobacteria. Infect Genet Evol 72 : 67 77.[CrossRef][PubMed]
29. Serafini A,, Boldrin F,, Palù G,, Manganelli R . 2009. Characterization of a Mycobacterium tuberculosis ESX-3 conditional mutant: essentiality and rescue by iron and zinc. J Bacteriol 191 : 6340 6344.[CrossRef][PubMed]
30. Siegrist MS,, Steigedal M,, Ahmad R,, Mehra A,, Dragset MS,, Schuster BM,, Philips JA,, Carr SA,, Rubin EJ . 2014. Mycobacterial Esx-3 requires multiple components for iron acquisition. mBio 5 : e01073-14.[CrossRef][PubMed]
31. Tufariello JM,, Chapman JR,, Kerantzas CA,, Wong KW,, Vilchèze C,, Jones CM,, Cole LE,, Tinaztepe E,, Thompson V,, Fenyö D,, Niederweis M,, Ueberheide B,, Philips JA,, Jacobs WR Jr . 2016. Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence. Proc Natl Acad Sci U S A 113 : E348 E357.[CrossRef][PubMed]
32. Bottai D,, Di Luca M,, Majlessi L,, Frigui W,, Simeone R,, Sayes F,, Bitter W,, Brennan MJ,, Leclerc C,, Batoni G,, Campa M,, Brosch R,, Esin S . 2012. Disruption of the ESX-5 system of Mycobacterium tuberculosis causes loss of PPE protein secretion, reduction of cell wall integrity and strong attenuation. Mol Microbiol 83 : 1195 1209.[CrossRef][PubMed]
33. Ates LS,, Ummels R,, Commandeur S,, van de Weerd R,, Sparrius M,, Weerdenburg E,, Alber M,, Kalscheuer R,, Piersma SR,, Abdallah AM,, Abd El Ghany M,, Abdel-Haleem AM,, Pain A,, Jiménez CR,, Bitter W,, Houben EN . 2015. Essential role of the ESX-5 secretion system in outer membrane permeability of pathogenic mycobacteria. PLoS Genet 11 : e1005190.[CrossRef][PubMed]
34. Gey van Pittius NC,, Sampson SL,, Lee H,, Kim Y,, van Helden PD,, Warren RM . 2006. Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions. BMC Evol Biol 6 : 95.[CrossRef][PubMed]
35. Bottai D,, Brosch R . 2009. Mycobacterial PE, PPE and ESX clusters: novel insights into the secretion of these most unusual protein families. Mol Microbiol 73 : 325 328.[CrossRef][PubMed]
36. Sayes F,, Sun L,, Di Luca M,, Simeone R,, Degaiffier N,, Fiette L,, Esin S,, Brosch R,, Bottai D,, Leclerc C,, Majlessi L . 2012. Strong immunogenicity and cross-reactivity of Mycobacterium tuberculosis ESX-5 type VII secretion: encoded PE-PPE proteins predicts vaccine potential. Cell Host Microbe 11 : 352 363.[CrossRef][PubMed]
37. Fishbein S,, van Wyk N,, Warren RM,, Sampson SL . 2015. Phylogeny to function: PE/PPE protein evolution and impact on Mycobacterium tuberculosis pathogenicity. Mol Microbiol 96 : 901 916.[CrossRef][PubMed]
38. Ates LS,, Dippenaar A,, Ummels R,, Piersma SR,, van der Woude AD,, van der Kuij K,, Le Chevalier F,, Mata-Espinosa D,, Barrios-Payán J,, Marquina-Castillo B,, Guapillo C,, Jiménez CR,, Pain A,, Houben ENG,, Warren RM,, Brosch R,, Hernández-Pando R,, Bitter W . 2018. Mutations in ppe38 block PE_PGRS secretion and increase virulence of Mycobacterium tuberculosis. Nat Microbiol 3 : 181 188.[CrossRef][PubMed]
39. Ates LS,, Dippenaar A,, Sayes F,, Pawlik A,, Bouchier C,, Ma L,, Warren RM,, Sougakoff W,, Majlessi L,, van Heijst JWJ,, Brossier F,, Brosch R . 2018. Unexpected genomic and phenotypic diversity of Mycobacterium africanum lineage 5 affects drug resistance, protein secretion, and immunogenicity. Genome Biol Evol 10 : 1858 1874.[CrossRef][PubMed]
40. Rosenberg OS,, Dovala D,, Li X,, Connolly L,, Bendebury A,, Finer-Moore J,, Holton J,, Cheng Y,, Stroud RM,, Cox JS . 2015. Substrates control multimerization and activation of the multi-domain ATPase motor of type VII secretion. Cell 161 : 501 512.[CrossRef][PubMed]
41. van Winden VJC,, Damen MPM,, Ummels R,, Bitter W,, Houben ENG . 2019. Protease domain and transmembrane domain of the type VII secretion mycosin protease determine system-specific functioning in mycobacteria. J Biol Chem 294 : 4806 4814.[CrossRef][PubMed]
42. Bosserman RE,, Champion PA . 2017. Esx systems and the mycobacterial cell envelope: what’s the connection? J Bacteriol 199 : e00131-17.[CrossRef][PubMed]
43. van Winden VJ,, Ummels R,, Piersma SR,, Jiménez CR,, Korotkov KV,, Bitter W,, Houben EN . 2016. Mycosins are required for the stabilization of the ESX-1 and ESX-5 type VII secretion membrane complexes. mBio 7 : 01471-16.[CrossRef][PubMed]
44. Fortune SM,, Jaeger A,, Sarracino DA,, Chase MR,, Sassetti CM,, Sherman DR,, Bloom BR,, Rubin EJ . 2005. Mutually dependent secretion of proteins required for mycobacterial virulence. Proc Natl Acad Sci U S A 102 : 10676 10681.[CrossRef][PubMed]
45. MacGurn JA,, Raghavan S,, Stanley SA,, Cox JS . 2005. A non-RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis. Mol Microbiol 57 : 1653 1663.[CrossRef][PubMed]
46. Chen JM . 2016. Mycosins of the mycobacterial type VII ESX secretion system: the glue that holds the party together. mBio 7 : 02062-16.[CrossRef][PubMed]
47. Lou Y,, Rybniker J,, Sala C,, Cole ST . 2017. EspC forms a filamentous structure in the cell envelope of Mycobacterium tuberculosis and impacts ESX-1 secretion. Mol Microbiol 103 : 26 38.[CrossRef][PubMed]
48. Phan TH,, Houben ENG . 2018. Bacterial secretion chaperones: the mycobacterial type VII case. FEMS Microbiol Lett 365 : fny197.[CrossRef]
49. Phan TH,, Ummels R,, Bitter W,, Houben EN . 2017. Identification of a substrate domain that determines system specificity in mycobacterial type VII secretion systems. Sci Rep 7 : 42704.[CrossRef][PubMed]
50. Sala C,, Odermatt NT,, Soler-Arnedo P,, Gülen MF,, von Schultz S,, Benjak A,, Cole ST . 2018. EspL is essential for virulence and stabilizes EspE, EspF and EspH levels in Mycobacterium tuberculosis. PLoS Pathog 14 : e1007491.[CrossRef][PubMed]
51. Coros A,, Callahan B,, Battaglioli E,, Derbyshire KM . 2008. The specialized secretory apparatus ESX-1 is essential for DNA transfer in Mycobacterium smegmatis. Mol Microbiol 69 : 794 808.[CrossRef][PubMed]
52. Derbyshire KM,, Gray TA . 2014. Distributive conjugal transfer: new insights into horizontal gene transfer and genetic exchange in mycobacteria. Microbiol Spectr 2 : MGM2-0022-2013.[CrossRef]
53. Gray TA,, Clark RR,, Boucher N,, Lapierre P,, Smith C,, Derbyshire KM . 2016. Intercellular communication and conjugation are mediated by ESX secretion systems in mycobacteria. Science 354 : 347 350.[CrossRef][PubMed]
54. Clark RR,, Judd J,, Lasek-Nesselquist E,, Montgomery SA,, Hoffmann JG,, Derbyshire KM,, Gray TA . 2018. Direct cell-cell contact activates SigM to express the ESX-4 secretion system in Mycobacterium smegmatis. Proc Natl Acad Sci U S A 115 : E6595 E6603.[CrossRef][PubMed]
55. Boritsch EC,, Khanna V,, Pawlik A,, Honoré N,, Navas VH,, Ma L,, Bouchier C,, Seemann T,, Supply P,, Stinear TP,, Brosch R . 2016. Key experimental evidence of chromosomal DNA transfer among selected tuberculosis-causing mycobacteria. Proc Natl Acad Sci U S A 113 : 9876 9881.[CrossRef][PubMed]
56. Supply P,, Marceau M,, Mangenot S,, Roche D,, Rouanet C,, Khanna V,, Majlessi L,, Criscuolo A,, Tap J,, Pawlik A,, Fiette L,, Orgeur M,, Fabre M,, Parmentier C,, Frigui W,, Simeone R,, Boritsch EC,, Debrie AS,, Willery E,, Walker D,, Quail MA,, Ma L,, Bouchier C,, Salvignol G,, Sayes F,, Cascioferro A,, Seemann T,, Barbe V,, Locht C,, Gutierrez MC,, Leclerc C,, Bentley SD,, Stinear TP,, Brisse S,, Médigue C,, Parkhill J,, Cruveiller S,, Brosch R . 2013. Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis. Nat Genet 45 : 172 179.[CrossRef][PubMed]
57. Boritsch EC,, Frigui W,, Cascioferro A,, Malaga W,, Etienne G,, Laval F,, Pawlik A,, Le Chevalier F,, Orgeur M,, Ma L,, Bouchier C,, Stinear TP,, Supply P,, Majlessi L,, Daffé M,, Guilhot C,, Brosch R . 2016. pks5-recombination-mediated surface remodelling in Mycobacterium tuberculosis emergence. Nat Microbiol 1 : 15019.[CrossRef][PubMed]
58. Godfroid M,, Dagan T,, Kupczok A . 2018. Recombination signal in Mycobacterium tuberculosis stems from reference-guided assemblies and alignment artefacts. Genome Biol Evol 10 : 1920 1926.[CrossRef][PubMed]
59. Orgeur M,, Brosch R . 2018. Evolution of virulence in the Mycobacterium tuberculosis complex. Curr Opin Microbiol 41 : 68 75.[CrossRef][PubMed]
60. Ates LS,, Brosch R . 2017. Discovery of the type VII ESX-1 secretion needle? Mol Microbiol 103 : 7 12.[CrossRef][PubMed]
61. Lewis KN,, Liao R,, Guinn KM,, Hickey MJ,, Smith S,, Behr MA,, Sherman DR . 2003. Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guérin attenuation. J Infect Dis 187 : 117 123.[CrossRef][PubMed]
62. Hsu T,, Hingley-Wilson SM,, Chen B,, Chen M,, Dai AZ,, Morin PM,, Marks CB,, Padiyar J,, Goulding C,, Gingery M,, Eisenberg D,, Russell RG,, Derrick SC,, Collins FM,, Morris SL,, King CH,, Jacobs WR Jr . 2003. The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue. Proc Natl Acad Sci U S A 100 : 12420 12425.[CrossRef][PubMed]
63. Stanley SA,, Raghavan S,, Hwang WW,, Cox JS . 2003. Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system. Proc Natl Acad Sci U S A 100 : 13001 13006.[CrossRef][PubMed]
64. Gao LY,, Guo S,, McLaughlin B,, Morisaki H,, Engel JN,, Brown EJ . 2004. A mycobacterial virulence gene cluster extending RD1 is required for cytolysis, bacterial spreading and ESAT-6 secretion. Mol Microbiol 53 : 1677 1693.[CrossRef][PubMed]
65. Pym AS,, Brodin P,, Brosch R,, Huerre M,, Cole ST . 2002. Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. Mol Microbiol 46 : 709 717.[CrossRef][PubMed]
66. van der Wel N,, Hava D,, Houben D,, Fluitsma D,, van Zon M,, Pierson J,, Brenner M,, Peters PJ . 2007. M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell 129 : 1287 1298.[CrossRef][PubMed]
67. Simeone R,, Bobard A,, Lippmann J,, Bitter W,, Majlessi L,, Brosch R,, Enninga J . 2012. Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and host cell death. PLoS Pathog 8 : e1002507.[CrossRef][PubMed]
68. Aguilo JI,, Alonso H,, Uranga S,, Marinova D,, Arbués A,, de Martino A,, Anel A,, Monzon M,, Badiola J,, Pardo J,, Brosch R,, Martin C . 2013. ESX-1-induced apoptosis is involved in cell-to-cell spread of Mycobacterium tuberculosis. Cell Microbiol 15 : 1994 2005.[CrossRef][PubMed]
69. Wong KW,, Jacobs WR Jr . 2011. Critical role for NLRP3 in necrotic death triggered by Mycobacterium tuberculosis. Cell Microbiol 13 : 1371 1384.[CrossRef][PubMed]
70. Wassermann R,, Gulen MF,, Sala C,, Perin SG,, Lou Y,, Rybniker J,, Schmid-Burgk JL,, Schmidt T,, Hornung V,, Cole ST,, Ablasser A . 2015. Mycobacterium tuberculosis differentially activates cGAS- and inflammasome-dependent intracellular immune responses through ESX-1. Cell Host Microbe 17 : 799 810.[CrossRef][PubMed]
71. Watson RO,, Bell SL,, MacDuff DA,, Kimmey JM,, Diner EJ,, Olivas J,, Vance RE,, Stallings CL,, Virgin HW,, Cox JS . 2015. The cytosolic sensor cGAS detects Mycobacterium tuberculosis DNA to induce type I interferons and activate autophagy. Cell Host Microbe 17 : 811 819.[CrossRef][PubMed]
72. Collins AC,, Cai H,, Li T,, Franco LH,, Li XD,, Nair VR,, Scharn CR,, Stamm CE,, Levine B,, Chen ZJ,, Shiloh MU . 2015. Cyclic GMP-AMP synthase is an innate immune DNA sensor for Mycobacterium tuberculosis. Cell Host Microbe 17 : 820 828.[CrossRef][PubMed]
73. Majlessi L,, Brosch R . 2015. Mycobacterium tuberculosis meets the cytosol: the role of cGAS in anti-mycobacterial immunity. Cell Host Microbe 17 : 733 735.[CrossRef][PubMed]
74. Kupz A,, Zedler U,, Stäber M,, Perdomo C,, Dorhoi A,, Brosch R,, Kaufmann SH . 2016. ESAT-6-dependent cytosolic pattern recognition drives noncognate tuberculosis control in vivo. J Clin Invest 126 : 2109 2122.[CrossRef][PubMed]
75. Gröschel MI,, Sayes F,, Shin SJ,, Frigui W,, Pawlik A,, Orgeur M,, Canetti R,, Honoré N,, Simeone R,, van der Werf TS,, Bitter W,, Cho SN,, Majlessi L,, Brosch R . 2017. Recombinant BCG expressing ESX-1 of Mycobacterium marinum combines low virulence with cytosolic immune signaling and improved TB protection. Cell Rep 18 : 2752 2765.[CrossRef][PubMed]
76. Augenstreich J,, Arbues A,, Simeone R,, Haanappel E,, Wegener A,, Sayes F,, Le Chevalier F,, Chalut C,, Malaga W,, Guilhot C,, Brosch R,, Astarie-Dequeker C . 2017. ESX-1 and phthiocerol dimycocerosates of Mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis. Cell Microbiol 19 : e12726.[CrossRef][PubMed]
77. Quigley J,, Hughitt VK,, Velikovsky CA,, Mariuzza RA,, El-Sayed NM,, Briken V . 2017. The cell wall lipid PDIM contributes to phagosomal escape and host cell exit of Mycobacterium tuberculosis. mBio 8 : e00148-17.[CrossRef][PubMed]
78. Barczak AK,, Avraham R,, Singh S,, Luo SS,, Zhang WR,, Bray MA,, Hinman AE,, Thompson M,, Nietupski RM,, Golas A,, Montgomery P,, Fitzgerald M,, Smith RS,, White DW,, Tischler AD,, Carpenter AE,, Hung DT . 2017. Systematic, multiparametric analysis of Mycobacterium tuberculosis intracellular infection offers insight into coordinated virulence. PLoS Pathog 13 : e1006363.[CrossRef][PubMed]
79. Skowyra ML,, Schlesinger PH,, Naismith TV,, Hanson PI . 2018. Triggered recruitment of ESCRT machinery promotes endolysosomal repair. Science 360 : eaar5-78.[CrossRef][PubMed]
80. Mehra A,, Zahra A,, Thompson V,, Sirisaengtaksin N,, Wells A,, Porto M,, Köster S,, Penberthy K,, Kubota Y,, Dricot A,, Rogan D,, Vidal M,, Hill DE,, Bean AJ,, Philips JA . 2013. Mycobacterium tuberculosis type VII secreted effector EsxH targets host ESCRT to impair trafficking. PLoS Pathog 9 : e1003734.[CrossRef][PubMed]
81. Mittal E,, Skowyra ML,, Uwase G,, Tinaztepe E,, Mehra A,, Köster S,, Hanson PI,, Philips JA . 2018. Mycobacterium tuberculosis type VII secretion system effectors differentially impact the ESCRT endomembrane damage response. mBio 9 : 01765-18.[CrossRef][PubMed]
82. Houben EN,, Korotkov KV,, Bitter W . 2014. Take five—type VII secretion systems of mycobacteria. Biochim Biophys Acta 1843 : 1707 1716.[CrossRef][PubMed]
83. Laencina L,, Dubois V,, Le Moigne V,, Viljoen A,, Majlessi L,, Pritchard J,, Bernut A,, Piel L,, Roux AL,, Gaillard JL,, Lombard B,, Loew D,, Rubin EJ,, Brosch R,, Kremer L,, Herrmann JL,, Girard-Misguich F . 2018. Identification of genes required for Mycobacterium abscessus growth in vivo with a prominent role of the ESX-4 locus. Proc Natl Acad Sci U S A 115 : E1002 E1011.[CrossRef][PubMed]
84. Sayes F,, Blanc C,, Ates LS,, Deboosere N,, Orgeur M,, Le Chevalier F,, Gröschel MI,, Frigui W,, Song OR,, Lo-Man R,, Brossier F,, Sougakoff W,, Bottai D,, Brodin P,, Charneau P,, Brosch R,, Majlessi L . 2018. Multiplexed quantitation of intraphagocyte Mycobacterium tuberculosis secreted protein effectors. Cell Rep 23 : 1072 1084.[CrossRef][PubMed]
85. Solans L,, Gonzalo-Asensio J,, Sala C,, Benjak A,, Uplekar S,, Rougemont J,, Guilhot C,, Malaga W,, Martín C,, Cole ST . 2014. The PhoP-dependent ncRNA Mcr7 modulates the TAT secretion system in Mycobacterium tuberculosis. PLoS Pathog 10 : e1004183.[CrossRef][PubMed]
86. Simeone R,, Sayes F,, Song O,, Gröschel MI,, Brodin P,, Brosch R,, Majlessi L . 2015. Cytosolic access of Mycobacterium tuberculosis: critical impact of phagosomal acidification control and demonstration of occurrence in vivo. PLoS Pathog 11 : e1004650.[CrossRef][PubMed]
87. Pym AS,, Brodin P,, Majlessi L,, Brosch R,, Demangel C,, Williams A,, Griffiths KE,, Marchal G,, Leclerc C,, Cole ST . 2003. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis. Nat Med 9 : 533 539.[CrossRef][PubMed]
88. Bottai D,, Frigui W,, Clark S,, Rayner E,, Zelmer A,, Andreu N,, de Jonge MI,, Bancroft GJ,, Williams A,, Brodin P,, Brosch R . 2015. Increased protective efficacy of recombinant BCG strains expressing virulence-neutral proteins of the ESX-1 secretion system. Vaccine 33 : 2710 2718.[CrossRef][PubMed]
89. Gengenbacher M,, Nieuwenhuizen N,, Vogelzang A,, Liu H,, Kaiser P,, Schuerer S,, Lazar D,, Wagner I,, Mollenkopf HJ,, Kaufmann SH . 2016. Deletion of nuoG from the vaccine candidate Mycobacterium bovis BCG Δ ureC:: hly improves protection against tuberculosis. mBio 7 : e00679-16.[CrossRef][PubMed]
90. Ates LS,, Sayes F,, Frigui W,, Ummels R,, Damen MPM,, Bottai D,, Behr MA,, van Heijst JWJ,, Bitter W,, Majlessi L,, Brosch R . 2018. RD5-mediated lack of PE_PGRS and PPE-MPTR export in BCG vaccine strains results in strong reduction of antigenic repertoire but little impact on protection. PLoS Pathog 14 : e1007139.[CrossRef][PubMed]
91. Aguilo N,, Gonzalo-Asensio J,, Alvarez-Arguedas S,, Marinova D,, Gomez AB,, Uranga S,, Spallek R,, Singh M,, Audran R,, Spertini F,, Martin C . 2017. Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis. Nat Commun 8 : 16085.[CrossRef][PubMed]
92. Sayes F,, Pawlik A,, Frigui W,, Gröschel MI,, Crommelynck S,, Fayolle C,, Cia F,, Bancroft GJ,, Bottai D,, Leclerc C,, Brosch R,, Majlessi L . 2016. CD4+ T cells recognizing PE/PPE antigens directly or via cross reactivity are protective against pulmonary Mycobacterium tuberculosis infection. PLoS Pathog 12 : e1005770.[CrossRef][PubMed]
93. Marinova D,, Gonzalo-Asensio J,, Aguilo N,, Martin C . 2017. MTBVAC from discovery to clinical trials in tuberculosis-endemic countries. Expert Rev Vaccines 16 : 565 576.[CrossRef][PubMed]

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