Skip to main content
SpringerLink
Log in

Type VII Secretion Systems in Gram-Positive Bacteria

  • Chapter
  • First Online:
Book cover Protein and Sugar Export and Assembly in Gram-positive Bacteria

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 404))

Abstract

Bacterial secretion systems are sophisticated molecular machines that fulfil a wide range of important functions, which reach from export/secretion of essential proteins or virulence factors to the implication in conjugation processes. In contrast to the widely distributed Sec and Twin Arginine Translocation (TAT) systems, the recently identified ESX/type VII systems show a more restricted distribution and are typical for mycobacteria and other high-GC Actinobacteria. Similarly, type VII-like secretion systems have been described in low-GC Gram-positive bacteria belonging to the phylum Firmicutes. While the most complex organization of type VII secretion systems currently known is found in slow-growing mycobacteria, which harbour up to 5 chromosomal-encoded systems (ESX-1 to ESX-5), much simpler organization is reported for type VII-like systems in Firmicutes. In this chapter, we describe common and divergent features of type VII- and type VII-like secretion pathways and also comment on their biological key roles, many of which are related to species-/genus-specific host–pathogen interactions and/or virulence mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdallah AM, Verboom T, Hannes F, Safi M, Strong M, Eisenberg D, Musters RJ, Vandenbroucke-Grauls CM, Appelmelk BJ, Luirink J, Bitter W (2006) A specific secretion system mediates PPE41 transport in pathogenic mycobacteria. Mol Microbiol 62:667–679

    Article  CAS  PubMed  Google Scholar 

  • Abdallah AM, Gey van Pittius NC, Champion PA, Cox J, Luirink J, Vandenbroucke-Grauls CM, Appelmelk BJ, Bitter W (2007) Type VII secretion system of mycobacteria show the way. Nat Rev Microbiol 5:883–891

    Article  CAS  PubMed  Google Scholar 

  • Abdallah AM, Verboom T, Weerdenburg EM, Gey van Pittius NC, Mahasha PW, Jimenez C, Parra M, Cadieux N, Brennan MJ, Appelmelk BJ, Bitter W (2009) PPE and PE_PGRS proteins of Mycobacterium marinum are transported via the type VII secretion system ESX-5. Mol Microbiol 73:329–340

    Article  CAS  PubMed  Google Scholar 

  • Adhikari RP, Novick RP (2008) Regulatory organization of the staphylococcal sae locus. Microbiology 154:949–959

    Article  CAS  PubMed  Google Scholar 

  • Agarwal N, Woolwine SC, Tyagi S, Bishai WR (2007) Characterization of the Mycobacterium tuberculosis sigma factor SigM by assessment of virulence and identification of SigM-dependent genes. Infect Immun 75:452–461

    Article  CAS  PubMed  Google Scholar 

  • Akpe San Roman S, Facey PD, Fernandez-Martinez L, Rodriguez C, Vallin C, Del Sol R, Dyson P (2010) A heterodimer of EsxA and EsxB is involved in sporulation and is secreted by a type VII secretion system in Streptomyces coelicolor. Microbiology 156:1719–1729

    Google Scholar 

  • Anderson M, Chen YH, Butler EK, Missiakas DM (2011) EsaD, a secretion factor for the Ess pathway in Staphylococcus aureus. J Bacteriol 193:1583–1589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson M, Aly KA, Chen YH, Missiakas D (2013) Secretion of atypical protein substrates by the ESAT-6 secretion system of Staphylococcus aureus. Mol Microbiol 90:734–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ates LS, Ummels R, Commandeur S, van der Weerd R, Sparrius M, Weerdenburg E, Alber M, Kalscheuer R, Piersma SR, Abdallah AM, Abd El Ghany M, Abdel-Haleem AM, Pain A, Jimenez 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Banu S, Honore N, Saint-Joanis B, Philpott D, Prevost MC, Cole ST (2002) Are the PE-PGRS proteins of Mycobacterium tuberculosis variable surface antigens? Mol Microbiol 44:9–19

    Article  CAS  PubMed  Google Scholar 

  • Baptista C, Barreto HC, Sao-Jose C (2013) High levels of DegU-P activate an Esat-6-like secretion system in Bacillus subtilis. PLoS ONE 8:e67840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 (2009a) Systematic genetic nomenclature for type VII secretion systems. PLoS Pathog 5:e1000507

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bitter W, Houben EN, Luirink J, Appelmelk BJ (2009b) Type VII secretion in mycobacteria: classification in line with cell envelope structure. Trends Microbiol 17:337–338

    Article  CAS  PubMed  Google Scholar 

  • Blasco B, Chen JM, Hartkoorn R, Sala C, Uplekar S, Rougemont J, Pojer F, Cole ST (2012) Virulence regulator EspR of Mycobacterium tuberculosis is a nucleoid-associated protein. PLoS Pathog 8:e1002621

    Article  PubMed  PubMed Central  Google Scholar 

  • Boritsch EC, Supply P, Honore N, Seemann T, Stinear TP, Brosch R (2014) A glimpse into the past and predictions for the future: the molecular evolution of the tuberculosis agent. Mol Microbiol 93:835–852

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Bottai D, Majlessi L, Simeone R, Frigui W, Laurent C, Lenormand P, Chen J, Rosenkrands I, Huerre M, Leclerc C, Cole ST, Brosch R (2011) ESAT-6 secretion-independent impact of ESX-1 genes espF and espG1 on virulence of Mycobacterium tuberculosis. J Infect Dis 203:1155–1164

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Bottai D, Stinear TP, Supply P, Brosch R (2014) Mycobacterial Pathogenomics and Evolution. Microbiol Spectr 2:MGM2-0025-2013

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Brennan MJ, Delogu G, Chen Y, Bardarov S, Kriakov J, Alavi M, Jacobs WR Jr (2001) Evidence that mycobacterial PE_PGRS proteins are cell surface constituents that influence interactions with other cells. Infect Immun 69:7326–7333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brodin P, Eiglmeier K, Marmiesse M, Billault A, Garnier T, Niemann S, Cole ST, Brosch R (2002) Bacterial artificial chromosome-based comparative genomic analysis identifies Mycobacterium microti as a natural ESAT-6 deletion mutant. Infect Immun 70:5568–5578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brodin P, Majlessi L, Brosch R, Smith D, Bancroft G, Clark S, Williams A, Leclerc C, Cole ST (2004a) Enhanced protection against tuberculosis by vaccination with recombinant Mycobacterium microti vaccine that induces T cell immunity against region of difference 1 antigens. J Infect Dis 190:115–122

    Article  CAS  PubMed  Google Scholar 

  • Brodin P, Rosenkrands I, Andersen P, Cole ST, Brosch R (2004b) ESAT-6 proteins: protective antigens and virulence factors? Trends Microbiol 12:500–508

    Article  CAS  PubMed  Google Scholar 

  • Brodin P, Majlessi L, Marsollier L, de Jonge MI, Bottai D, Demangel C, Hinds J, Neyrolles O, Butcher PD, Leclerc C, Cole ST, Brosch R (2006) Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on immunogenicity and virulence. Infect Immun 74:88–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brodin P, Poquet Y, Levillain F, Peguillet I, Larrouy-Maumus G, Gilleron M, Ewann F, Christophe T, Fenistein D, Jang J, Jang MS, Park SJ, Rauzier J, Carralot JP, Shrimpton R, Genovesio A, Gonzalo-Asensio JA, Puzo G, Martin C, Brosch R, Stewart GR, Gicquel B, Neyrolles O (2010) High content phenotypic cell-based visual screen identifies Mycobacterium tuberculosis acyltrehalose-containing glycolipids involved in phagosome remodeling. PLoS Pathog 6:e1001100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brown GD, Dave JA, Gey van Pittius NC, Stevens L, Ehlers MR, Beyers AD (2000) The mycosins of Mycobacterium tuberculosis H37Rv: a family of subtilisin-like serine proteases. Gene 254:147–155

    Article  CAS  PubMed  Google Scholar 

  • Burts ML, Williams WA, Debord K, Missiakas DM (2005) EsxA and EsxB are secreted by an ESAT-6-like system that is required for the pathogenesis of Staphylococcus aureus infections. Proc Natl Acad Sci U S A 102:1169–1174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burts ML, DeDent AC, Missiakas DM (2008) EsaC substrate for the ESAT-6 secretion pathway and its role in persistent infections of Staphylococcus aureus. Mol Microbiol 69:736–746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carlsson F, Joshi SA, Rangell L, Brown EJ (2009) Polar localization of virulence-related Esx-1 secretion in mycobacteria. PLoS Pathog 5:e1000285

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cascioferro A, Delogu G, Colone M, Sali M, Stringaro A, Arancia G, Fadda G, Palu G, Manganelli R (2007) PE is a functional domain responsible for protein translocation and localization on mycobacterial cell wall. Mol Microbiol 66:1536–1547

    CAS  PubMed  Google Scholar 

  • Casonato S, Cervantes Sanchez A, Haruki H, Rengifo Gonzalez M, Provvedi R, Dainese E, Jaouen T, Gola S, Bini E, Vicente M, Johnsson K, Ghisotti D, Palu G, Hernandez-Pando R, Manganelli R (2012) WhiB5, a transcriptional regulator that contributes to Mycobacterium tuberculosis virulence and reactivation. Infect Immun 80:3132–3144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Champion PA, Stanley SA, Champion MM, Brown EJ, Cox JS (2006) C-terminal signal sequence promotes virulence factor secretion in Mycobacterium tuberculosis. Science 313:1632–1636

    Article  PubMed  CAS  Google Scholar 

  • Champion PA, Champion MM, Manzanillo P, Cox JS (2009) ESX-1 secreted virulence factors are recognized by multiple cytosolic AAA ATPases in pathogenic mycobacteria. Mol Microbiol 73:950–962

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chaturvedi R, Bansal K, Narayana Y, Kapoor N, Sukumar N, Togarsimalemath SK, Chandra N, Mishra S, Ajitkumar P, Joshi B, Katoch VM, Patil SA, Balaji KN (2010) The multifunctional PE_PGRS11 protein from Mycobacterium tuberculosis plays a role in regulating resistance to oxidative stress. J Biol Chem 285:30389–30403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen YH, Anderson M, Hendrickx AP, Missiakas D (2012) Characterization of EssB, a protein required for secretion of ESAT-6 like proteins in Staphylococcus aureus. BMC Microbiol 12:219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen JM, Zhang M, Rybniker J, Boy-Rottger S, Dhar N, Pojer F, Cole ST (2013) Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA-independent virulence. Mol Microbiol 89:1154–1166

    Article  CAS  PubMed  Google Scholar 

  • Cheung AL, Bayer AS, Zhang G, Gresham H, Xiong YQ (2004) Regulation of virulence determinants in vitro and in vivo in Staphylococcus aureus. FEMS Immunol Med Microbiol 40:1–9

    Article  CAS  PubMed  Google Scholar 

  • Christie PJ (2001) Type IV secretion: intercellular transfer of macromolecules by systems ancestrally related to conjugation machines. Mol Microbiol 40:294–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Christophe T, Jackson M, Jeon HK, Fenistein D, Contreras-Dominguez M, Kim J, Genovesio A, Carralot JP, Ewann F, Kim EH, Lee SY, Kang S, Seo MJ, Park EJ, Skovierova H, Pham H, Riccardi G, Nam JY, Marsollier L, Kempf M, Joly-Guillou ML, Oh T, Shin WK, No Z, Nehrbass U, Brosch R, Cole ST, Brodin P (2009) High content screening identifies decaprenyl-phosphoribose 2’ epimerase as a target for intracellular antimycobacterial inhibitors. PLoS Pathog 5:e1000645

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Clement S, Vaudaux P, Francois P, Schrenzel J, Huggler E, Kampf S, Chaponnier C, Lew D, Lacroix JS (2005) Evidence of an intracellular reservoir in the nasal mucosa of patients with recurrent Staphylococcus aureus rhinosinusitis. J Infect Dis 192:1023–1028

    Article  PubMed  Google Scholar 

  • Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, 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

    Article  CAS  PubMed  Google Scholar 

  • Collins AC, Cai H, Li T, Franco LH, Li X-D, Nair VR, Scharn CR, Stamm CE, Levine B, Chen ZJ, Shiloh MU (2015) Cyclic GMP-AMP Synthase (cGAS) is an innate immune DNA sensor for Mycobacterium tuberculosis. Cell Host Microbe 17:820–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Converse SE, Cox JS (2005) A protein secretion pathway critical for Mycobacterium tuberculosis virulence is conserved and functional in Mycobacterium smegmatis. J Bacteriol 187:1238–1245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Copin R, Coscolla M, Seiffert SN, Bothamley G, Sutherland J, Mbayo G, Gagneux S, Ernst JD (2014) Sequence diversity in the pe_pgrs genes of Mycobacterium tuberculosis is independent of human T cell recognition. MBio 5:e00960–13

    Google Scholar 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Costa TR, Felisberto-Rodrigues C, Meir A, Prevost MS, Redzej A, Trokter M, Waksman G (2015) Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nat Rev Microbiol 13:343–359

    Article  CAS  PubMed  Google Scholar 

  • Daleke MH, Cascioferro A, de Punder K, Ummels R, Abdallah AM, van der Wel N, Peters PJ, Luirink J, Manganelli R, Bitter W (2011) Conserved Pro-Glu (PE) and Pro-Pro-Glu (PPE) protein domains target LipY lipases of pathogenic mycobacteria to the cell surface via the ESX-5 pathway. J Biol Chem 286:19024–19034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daleke MH, Ummels R, Bawono P, Heringa J, Vandenbroucke-Grauls CM, Luirink J, Bitter W (2012) General secretion signal for the mycobacterial type VII secretion pathway. Proc Natl Acad Sci U S A 109:11342–11347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dave JA, Gey van Pittius NC, Beyers AD, Ehlers MR, Brown GD (2002) Mycosin-1, a subtilisin-like serine protease of Mycobacterium tuberculosis, is cell wall-associated and expressed during infection of macrophages. BMC Microbiol 2:30

    Article  PubMed  PubMed Central  Google Scholar 

  • de Jonge MI, Pehau-Arnaudet G, Fretz MM, Romain F, Bottai D, Brodin P, Honore N, Marchal G, Jiskoot W, England P, Cole ST, Brosch R (2007) ESAT-6 from Mycobacterium tuberculosis dissociates from its putative chaperone CFP-10 under acidic conditions and exhibits membrane-lysing activity. J Bacteriol 189:6028–6034

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • De Leon J, Jiang G, Ma Y, Rubin E, Fortune S, Sun J (2012) Mycobacterium tuberculosis ESAT-6 exhibits a unique membrane-interacting activity that is not found in its ortholog from non-pathogenic Mycobacterium smegmatis. J Biol Chem 287:44184–44191

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Deb C, Daniel J, Sirakova TD, Abomoelak B, Dubey VS, Kolattukudy PE (2006) A novel lipase belonging to the hormone-sensitive lipase family induced under starvation to utilize stored triacylglycerol in Mycobacterium tuberculosis. J Biol Chem 281:3866–3875

    Article  CAS  PubMed  Google Scholar 

  • Delogu G, Brennan MJ (2001) Comparative immune response to PE and PE_PGRS antigens of Mycobacterium tuberculosis. Infect Immun 69:5606–5611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Luca M, Bottai D, Batoni G, Orgeur M, Aulicino A, Counoupas C, Campa M, Brosch R, Esin S (2012) The ESX-5 associated eccB-eccC locus Is essential for Mycobacterium tuberculosis viability. PLoS ONE 7:e52059

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dong D, Wang D, Li M, Wang H, Yu J, Wang C, Liu J, Gao Q (2012) PPE38 modulates the innate immune response and is required for Mycobacterium marinum virulence. Infect Immun 80:43–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dorhoi A, Nouailles G, Jorg S, Hagens K, Heinemann E, Pradl L, Oberbeck-Muller D, Duque-Correa MA, Reece ST, Ruland J, Brosch R, Tschopp J, Gross O, Kaufmann SHE (2012) Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis. Eur J Immunol 42:374–384

    Article  CAS  PubMed  Google Scholar 

  • Ekiert DC, Cox JS (2014) Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion. Proc Natl Acad Sci U S A 111:14758–14763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flint JL, Kowalski JC, Karnati PK, Derbyshire KM (2004) The RD1 virulence locus of Mycobacterium tuberculosis regulates DNA transfer in Mycobacterium smegmatis. Proc Natl Acad Sci U S A 101:12598–12603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fraunholz M, Sinha B (2012) Intracellular Staphylococcus aureus: live-in and let die. Front Cell Infect Microbiol 2:43

    Article  PubMed  PubMed Central  Google Scholar 

  • Frigui W, Bottai D, Majlessi L, Monot M, Josselin E, Brodin P, Garnier T, Gicquel B, Martin C, Leclerc C, Cole S, Brosch R (2008) Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP. PLoS Pathog 4:e33

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fyans JK, Bignell D, Loria R, Toth I, Palmer T (2013) The ESX/type VII secretion system modulates development, but not virulence, of the plant pathogen Streptomyces scabies. Mol Plant Pathol 14:119–130

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Gardy JL, Laird MR, Chen F, Rey S, Walsh CJ, Ester M, Brinkman FS (2005) PSORTb v. 2.0: expanded prediction of bacterial protein subcellular localization and insights gained from comparative proteome analysis. Bioinformatics 21:617–623

    Article  CAS  PubMed  Google Scholar 

  • Garufi G, Butler E, Missiakas D (2008) ESAT-6-like protein secretion in Bacillus anthracis. J Bacteriol 190:7004–7011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garzoni C, Kelley WL (2009) Staphylococcus aureus: new evidence for intracellular persistence. Trends Microbiol 17:59–65

    Article  CAS  PubMed  Google Scholar 

  • Gey Van Pittius NC, Gamieldien J, Hide W, Brown GD, Siezen RJ, Beyers AD (2001) The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G + C Gram-positive bacteria. Genome Biol 2:RESEARCH0044

    Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Giraudo AT, Cheung AL, Nagel R (1997) The sae locus of Staphylococcus aureus controls exoprotein synthesis at the transcriptional level. Arch Microbiol 168:53–58

    Article  CAS  PubMed  Google Scholar 

  • Goldstone RM, Goonesekera SD, Bloom BR, Sampson SL (2009) The transcriptional regulator Rv0485 modulates the expression of a pe and ppe gene pair and is required for Mycobacterium tuberculosis virulence. Infect Immun 77:4654–4667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalo-Asensio J, Malaga W, Pawlik A, Astarie-Dequeker C, Passemar C, Moreau F, Laval F, Daffe M, Martin C, Brosch R, Guilhot C (2014) Evolutionary history of tuberculosis shaped by conserved mutations in the PhoPR virulence regulator. Proc Natl Acad Sci U S A 111:11491–11496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gordon BR, Li Y, Wang L, Sintsova A, van Bakel H, Tian S, Navarre WW, Xia B, Liu J (2010) Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 107:5154–5159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gray TA, Krywy JA, Harold J, Palumbo MJ, Derbyshire KM (2013) Distributive conjugal transfer in mycobacteria generates progeny with meiotic-like genome-wide mosaicism, allowing mapping of a mating identity locus. PLoS Biol 11:e1001602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guinn KM, Hickey MJ, Mathur SK, Zakel KL, Grotzke JE, Lewinsohn DM, Smith S, Sherman DR (2004) Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis. Mol Microbiol 51:359–370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann C, Leis A, Niederweis M, Plitzko JM, Engelhardt H (2008) Disclosure of the mycobacterial outer membrane: cryo-electron tomography and vitreous sections reveal the lipid bilayer structure. Proc Natl Acad Sci U S A 105:3963–3967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Houben D, Demangel C, van Ingen J, Perez J, Baldeon L, Abdallah AM, Caleechurn L, Bottai D, van Zon M, de Punder K, van der Laan T, Kant A, Bossers-de Vries R, Willemsen P, Bitter W, van Soolingen D, Brosch R, van der Wel N, Peters PJ (2012a) ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria. Cell Microbiol 14:1287–1298

    Article  CAS  PubMed  Google Scholar 

  • Houben EN, Bestebroer J, Ummels R, Wilson L, Piersma SR, Jimenez CR, Ottenhoff TH, Luirink J, Bitter W (2012b) Composition of the type VII secretion system membrane complex. Mol Microbiol 86:472–484

    Article  CAS  PubMed  Google Scholar 

  • Houben EN, Korotkov KV, Bitter W (2014) Take five - Type VII secretion systems of Mycobacteria. Biochim Biophys Acta 1844:1707–1716

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsueh YH, Cozy LM, Sham LT, Calvo RA, Gutu AD, Winkler ME, Kearns DB (2011) DegU-phosphate activates expression of the anti-sigma factor FlgM in Bacillus subtilis. Mol Microbiol 81:1092–1108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hunt DM, Sweeney NP, Mori L, Whalan RH, Comas I, Norman L, Cortes T, Arnvig KB, Davis EO, Stapleton MR, Green J, Buxton RS (2012) Long-range transcriptional control of an operon necessary for virulence-critical ESX-1 secretion in Mycobacterium tuberculosis. J Bacteriol 194:2307–2320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huppert LA, Ramsdell TL, Chase MR, Sarracino DA, Fortune SM, Burton BM (2014) The ESX system in Bacillus subtilis mediates protein secretion. PLoS ONE 9:e96267

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Iantomasi R, Sali M, Cascioferro A, Palucci I, Zumbo A, Soldini S, Rocca S, Greco E, Maulucci G, De Spirito M, Fraziano M, Fadda G, Manganelli R, Delogu G (2012) PE_PGRS30 is required for the full virulence of Mycobacterium tuberculosis. Cell Microbiol 14:356–367

    Article  CAS  PubMed  Google Scholar 

  • Ilghari D, Lightbody KL, Veverka V, Waters LC, Muskett FW, Renshaw PS, Carr MD (2011) Solution structure of the Mycobacterium tuberculosis EsxG.EsxH complex: functional implications and comparisons with other M. tuberculosis Esx family complexes. J Biol Chem 286:29993–30002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iyer LM, Makarova KS, Koonin EV, Aravind L (2004) Comparative genomics of the FtsK-HerA superfamily of pumping ATPases: implications for the origins of chromosome segregation, cell division and viral capsid packaging. Nucleic Acids Res 32:5260–5279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kneuper H, Cao ZP, Twomey KB, Zoltner M, Jager F, Cargill JS, Chalmers J, van der Kooi-Pol MM, van Dijl JM, Ryan RP, Hunter WN, Palmer T (2014) Heterogeneity in ess transcriptional organization and variable contribution of the Ess/Type VII protein secretion system to virulence across closely related Staphylocccus aureus strains. Mol Microbiol 93:928–943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi K (2007) Gradual activation of the response regulator DegU controls serial expression of genes for flagellum formation and biofilm formation in Bacillus subtilis. Mol Microbiol 66:395–409

    Article  CAS  PubMed  Google Scholar 

  • Korea CG, Balsamo G, Pezzicoli A, Merakou C, Tavarini S, Bagnoli F, Serruto D, Unnikrishnan M (2014) Staphylococcal Esx proteins modulate apoptosis and release of intracellular Staphylococcus aureus during infection in epithelial cells. Infect Immun 82:4144–4153

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Korotkova N, Freire D, Phan TH, Ummels R, Creekmore CC, Evans TJ, Wilmanns M, Bitter W, Parret AH, Houben EN, Korotkov KV (2014) Structure of the Mycobacterium tuberculosis type VII secretion system chaperone EspG5 in complex with PE25-PPE41 dimer. Mol Microbiol 94:367–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Korotkova N, Piton J, Wagner JM, Boy-Rottger S, Japaridze A, Evans TJ, Cole ST, Pojer F, Korotkov KV (2015) Structure of EspB, a secreted substrate of the ESX-1 secretion system of Mycobacterium tuberculosis. J Struct Biol 191:236–244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le Chevalier F, Cascioferro A, Majlessi L, Herrmann JL, Brosch R (2014) Mycobacterium tuberculosis evolutionary pathogenesis and its putative impact on drug development. Future Microbiol 9:969–985

    Article  CAS  PubMed  Google Scholar 

  • Lewis KN, Liao R, Guinn KM, Hickey MJ, Smith S, Behr MA, Sherman DR (2003) Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guerin attenuation. J Infect Dis 187:117–123

    Article  PubMed  Google Scholar 

  • Li Y, Miltner E, Wu M, Petrofsky M, Bermudez LE (2005) A Mycobacterium avium PPE gene is associated with the ability of the bacterium to grow in macrophages and virulence in mice. Cell Microbiol 7:539–548

    Article  CAS  PubMed  Google Scholar 

  • Lopez D, Kolter R (2010) Extracellular signals that define distinct and coexisting cell fates in Bacillus subtilis. FEMS Microbiol Rev 34:134–149

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Maciag A, Dainese E, Rodriguez GM, Milano A, Provvedi R, Pasca MR, Smith I, Palu G, Riccardi G, Manganelli R (2007) Global analysis of the Mycobacterium tuberculosis Zur (FurB) regulon. J Bacteriol 189:730–740

    Article  CAS  PubMed  Google Scholar 

  • Mader U, Antelmann H, Buder T, Dahl MK, Hecker M, Homuth G (2002) Bacillus subtilis functional genomics: genome-wide analysis of the DegS-DegU regulon by transcriptomics and proteomics. Mol Genet Genomics 268:455–467

    Article  CAS  PubMed  Google Scholar 

  • Mahairas GG, Sabo PJ, Hickey MJ, Singh DC, Stover CK (1996) Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J Bacteriol 178:1274–1282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Majlessi L, Brosch R (2015) Mycobacterium tuberculosis meets the cytosol: The role of cGAS in anti-mycobacterial immunity. Cell Host Microbe 17:733–735

    Article  CAS  PubMed  Google Scholar 

  • Majlessi L, Prados-Rosales R, Casadevall A, Brosch R (2015) Release of mycobacterial antigens. Immunol Rev 264:25–45

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin B, Chon JS, MacGurn JA, Carlsson F, Cheng TL, Cox JS, Brown EJ (2007) A mycobacterium ESX-1-secreted virulence factor with unique requirements for export. PLoS Pathog 3:e105

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mehra A, Zahra A, Thompson V, Sirisaengtaksin N, Wells A, Porto M, Koster 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mishra BB, Moura-Alves P, Sonawane A, Hacohen N, Griffiths G, Moita LF, Anes E (2010) Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome. Cell Microbiol 12:1046–1063

    Article  CAS  PubMed  Google Scholar 

  • Murray EJ, Kiley TB, Stanley-Wall NR (2009) A pivotal role for the response regulator DegU in controlling multicellular behaviour. Microbiology 155:1–8

    Article  CAS  PubMed  Google Scholar 

  • Novick RP (2003) Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol Microbiol 48:1429–1449

    Article  CAS  PubMed  Google Scholar 

  • Ogura M, Yamaguchi H, Yoshida K, Fujita Y, Tanaka T (2001) DNA microarray analysis of Bacillus subtilis DegU, ComA and PhoP regulons: an approach to comprehensive analysis of B. subtilis two-component regulatory systems. Nucleic Acids Res 29:3804–3813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohol YM, Goetz DH, Chan K, Shiloh MU, Craik CS, Cox JS (2010) Mycobacterium tuberculosis MycP1 protease plays a dual role in regulation of ESX-1 secretion and virulence. Cell Host Microbe 7:210–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pallen MJ (2002) The ESAT-6/WXG100 superfamily—and a new Gram-positive secretion system? Trends Microbiol 10:209–212

    Article  CAS  PubMed  Google Scholar 

  • Pang X, Samten B, Cao G, Wang X, Tvinnereim AR, Chen XL, Howard ST (2013) MprAB regulates the espA operon in Mycobacterium tuberculosis and modulates ESX-1 function and host cytokine response. J Bacteriol 195:66–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poulsen C, Panjikar S, Holton SJ, Wilmanns M, Song YH (2014) WXG100 protein superfamily consists of three subfamilies and exhibits an alpha-helical C-terminal conserved residue pattern. PLoS ONE 9:e89313

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Raghavan S, Manzanillo P, Chan K, Dovey C, Cox J (2008) Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 454:717–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramakrishnan L, Federspiel NA, Falkow S (2000) Granuloma-specific expression of Mycobacterium virulence proteins from the glycine-rich PE-PGRS family. Science 288:1436–1439

    Article  CAS  PubMed  Google Scholar 

  • Raman S, Puyang X, Cheng TY, Young DC, Moody DB, Husson RN (2006) Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis. J Bacteriol 188:8460–8468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramsdell TL, Huppert LA, Sysoeva TA, Fortune SM, Burton BM (2015) Linked domain architectures allow for specialization of function in the FtsK/SpoIIIE ATPases of ESX secretion systems. J Mol Biol 427:1119–1132

    Article  CAS  PubMed  Google Scholar 

  • Renshaw PS, Lightbody KL, Veverka V, Muskett FW, Kelly G, Frenkiel TA, Gordon SV, Hewinson RG, Burke B, Norman J, Williamson RA, Carr MD (2005) Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6. EMBO J 24:2491–2498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rickman L, Scott C, Hunt DM, Hutchinson T, Menendez MC, Whalan R, Hinds J, Colston MJ, Green J, Buxton RS (2005) A member of the cAMP receptor protein family of transcription regulators in Mycobacterium tuberculosis is required for virulence in mice and controls transcription of the rpfA gene coding for a resuscitation promoting factor. Mol Microbiol 56:1274–1286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodriguez GM, Voskuil MI, Gold B, Schoolnik GK, Smith I (2002) ideR, an essential gene in Mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect Immun 70:3371–3381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Romagnoli A, Etna MP, Giacomini E, Pardini M, Remoli ME, Corazzari M, Falasca L, Goletti D, Gafa V, Simeone R, Delogu G, Piacentini M, Brosch R, Fimia GM, Coccia EM (2012) ESX-1 dependent impairment of autophagic flux by Mycobacterium tuberculosis in human dendritic cells. Autophagy 8:1357–1370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ryan AA, Nambiar JK, Wozniak TM, Roediger B, Shklovskaya E, Britton WJ, Fazekas de St Groth B, Triccas JA (2009) Antigen load governs the differential priming of CD8 T cells in response to the bacille Calmette Guerin vaccine or Mycobacterium tuberculosis infection. J Immunol 182:7172–7177

    Article  CAS  PubMed  Google Scholar 

  • Rybniker J, Chen JM, Sala C, Hartkoorn RC, Vocat A, Benjak A, Boy-Rottger S, Zhang M, Szekely R, Greff Z, Orfi L, Szabadkai I, Pato J, Keri G, Cole ST (2014) Anticytolytic screen identifies inhibitors of mycobacterial virulence protein secretion. Cell Host Microbe 16:538–548

    Article  CAS  PubMed  Google Scholar 

  • Sachse F, Becker K, von Eiff C, Metze D, Rudack C (2010) Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL-6 in nasal epithelial cells in vitro. Allergy 65:1430–1437

    Article  CAS  PubMed  Google Scholar 

  • Sampson SL, Lukey P, Warren RM, van Helden PD, Richardson M, Everett MJ (2001) Expression, characterization and subcellular localization of the Mycobacterium tuberculosis PPE gene Rv1917c. Tuberculosis (Edinb) 81:305–317

    Article  CAS  Google Scholar 

  • Sani M, Houben EN, Geurtsen J, Pierson J, de Punder K, van Zon M, Wever B, Piersma SR, Jimenez CR, Daffe M, Appelmelk BJ, Bitter W, van der Wel N, Peters PJ (2010) Direct visualization by cryo-EM of the mycobacterial capsular layer: a labile structure containing ESX-1-secreted proteins. PLoS Pathog 6:e1000794

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Schneewind O, Missiakas DM (2012) Protein secretion and surface display in Gram-positive bacteria. Philos Trans R Soc Lond B Biol Sci 367:1123–1139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Serafini A, Boldrin F, Palu 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah S, Cannon JR, Fenselau C, Briken V (2015) A duplicated ESAT-6 region of ESX-5 is involved in protein export and virulence of mycobacteria. Infect Immun 83:4349–4361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shukla A, Pallen M, Anthony M, White SA (2010) The homodimeric GBS1074 from Streptococcus agalactiae. Acta Crystallogr, Sect F: Struct Biol Cryst Commun 66:1421–1425

    Article  CAS  Google Scholar 

  • Siegrist MS, Unnikrishnan M, McConnell MJ, Borowsky M, Cheng TY, Siddiqi N, Fortune SM, Moody DB, Rubin EJ (2009) Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition. Proc Natl Acad Sci U S A 106:18792–18797

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simeone R, Sayes F, Song O, Groschel 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Solans L, Aguilo N, Samper S, Pawlik A, Frigui W, Martin C, Brosch R, Gonzalo-Asensio J (2014) A specific polymorphism in Mycobacterium tuberculosis H37Rv causes differential ESAT-6 expression and identifies WhiB6 as a novel ESX-1 component. Infect Immun 82:3446–3456

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Solomonson M, Setiaputra D, Makepeace KA, Lameignere E, Petrotchenko EV, Conrady DG, Bergeron JR, Vuckovic M, DiMaio F, Borchers CH, Yip CK, Strynadka NC (2015) Structure of EspB from the ESX-1 type VII secretion system and insights into its export mechanism. Structure 23:571–583

    Article  CAS  PubMed  Google Scholar 

  • Song H, Sandie R, Wang Y, Andrade-Navarro MA, Niederweis M (2008) Identification of outer membrane proteins of Mycobacterium tuberculosis. Tuberculosis (Edinb) 88:526–544

    Article  CAS  Google Scholar 

  • Sonnhammer EL, von Heijne G, Krogh A (1998) A hidden Markov model for predicting transmembrane helices in protein sequences. Proc Int Conf Intell Syst Mol Biol 6:175–182

    CAS  PubMed  Google Scholar 

  • Sorensen 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stamm LM, Morisaki JH, Gao LY, Jeng RL, McDonald KL, Roth R, Takeshita S, Heuser J, Welch MD, Brown EJ (2003) Mycobacterium marinum escapes from phagosomes and is propelled by actin-based motility. J Exp Med 198:1361–1368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stanley SA, Cox JS (2013) Host-pathogen interactions during Mycobacterium tuberculosis infections. Curr Top Microbiol Immunol 374:211–241

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stanley SA, Johndrow JE, Manzanillo P, Cox JS (2007) The Type I IFN Response to Infection with Mycobacterium tuberculosis Requires ESX-1-Mediated Secretion and Contributes to Pathogenesis. J Immunol 178:3143–3152

    Article  CAS  PubMed  Google Scholar 

  • Strong M, Sawaya MR, Wang S, Phillips M, Cascio D, Eisenberg D (2006) Toward the structural genomics of complexes: crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 103:8060–8065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sundaramoorthy R, Fyfe PK, Hunter WN (2008) Structure of Staphylococcus aureus EsxA suggests a contribution to virulence by action as a transport chaperone and/or adaptor protein. J Mol Biol 383:603–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Sysoeva TA, Zepeda-Rivera MA, Huppert LA, Burton BM (2014) Dimer recognition and secretion by the ESX secretion system in Bacillus subtilis. Proc Natl Acad Sci U S A 111:7653–7658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Teutschbein J, Schumann G, Mollmann U, Grabley S, Cole ST, Munder T (2009) A protein linkage map of the ESAT-6 secretion system 1 (ESX-1) of Mycobacterium tuberculosis. Microbiol Res 164:253–259

    Article  CAS  PubMed  Google Scholar 

  • Tuchscherr L, Medina E, Hussain M, Volker W, Heitmann V, Niemann S, Holzinger D, Roth J, Proctor RA, Becker K, Peters G, Loffler B (2011) Staphylococcus aureus phenotype switching: an effective bacterial strategy to escape host immune response and establish a chronic infection. EMBO Mol Med 3:129–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ummels R, Abdallah AM, Kuiper V, Aajoud 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

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • van der Woude AD, Luirink J, Bitter W (2013) Getting across the cell envelope: mycobacterial protein secretion. Curr Top Microbiol Immunol 374:109–134

    PubMed  Google Scholar 

  • Voskuil MI, Schnappinger D, Rutherford R, Liu Y, Schoolnik GK (2004) Regulation of the Mycobacterium tuberculosis PE/PPE genes. Tuberculosis (Edinb) 84:256–262

    Article  CAS  Google Scholar 

  • Wagner JM, Evans TJ, Chen J, Zhu H, Houben EN, Bitter W, Korotkov KV (2013) Understanding specificity of the mycosin proteases in ESX/type VII secretion by structural and functional analysis. J Struct Biol 184:115–128

    Article  CAS  PubMed  Google Scholar 

  • Walters SB, Dubnau E, Kolesnikova I, Laval F, Daffe M, Smith I (2006) The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol Microbiol 60:312–330

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Engohang-Ndong J, Smith I (2007) Structure of the DNA-binding domain of the response regulator PhoP from Mycobacterium tuberculosis. Biochemistry 46:14751–14761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 aActivates cGAS- and inflammasome-dependent intracellular immune responses through ESX-1. Cell Host Microbe 17:799–810

    Article  CAS  PubMed  Google Scholar 

  • Watson RO, Manzanillo PS, Cox JS (2012) Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell 150:803–815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Way SS, Wilson CB (2005) The Mycobacterium tuberculosis ESAT-6 homologue in Listeria monocytogenes is dispensable for growth in vitro and in vivo. Infect Immun 73:6151–6153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong KW, Jacobs WR Jr (2011) Critical role for NLRP3 in necrotic death triggered by Mycobacterium tuberculosis. Cell Microbiol 13:1371–1384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang M, Chen JM, Sala C, Rybniker J, Dhar N, Cole ST (2014) EspI regulates the ESX-1 secretion system in response to ATP levels in Mycobacterium tuberculosis. Mol Microbiol 93:1057–1065

    Google Scholar 

  • Zuber B, Chami M, Houssin C, Dubochet J, Griffiths G, Daffe M (2008) Direct visualization of the outer membrane of mycobacteria and corynebacteria in their native state. J Bacteriol 190:5672–5680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Support by the European Community (Grant H2020-PHC-643381) and the Fondation pour la Recherche Médicale FRM (DEQ 20130326471) is gratefully acknowledged. M.I.G. is supported by an MD–PhD grant of the University of Groningen, The Netherlands.

Author information

Authors and Affiliations

  1. Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, University of Pisa, Pisa, Italy

    Daria Bottai

  2. Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris, France

    Matthias I. Gröschel & Roland Brosch

  3. Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Matthias I. Gröschel

Authors
  1. Daria Bottai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthias I. Gröschel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roland Brosch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roland Brosch .

Editor information

Editors and Affiliations

  1. GSK Vaccines , Siena, Siena, Italy

    Fabio Bagnoli

  2. GSK Vaccines , Siena, Italy

    Rino Rappuoli

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bottai, D., Gröschel, M.I., Brosch, R. (2015). Type VII Secretion Systems in Gram-Positive Bacteria. In: Bagnoli, F., Rappuoli, R. (eds) Protein and Sugar Export and Assembly in Gram-positive Bacteria . Current Topics in Microbiology and Immunology, vol 404. Springer, Cham. https://doi.org/10.1007/82_2015_5015

Download citation

Publish with us

Policies and ethics

Search

Navigation