title: ESAT-6 secretion-independent impact of ESX-1 genes espF and espG1 on virulence of Mycobacterium tuberculosis.
abstract: BACKGROUND
  The pathogenesis of Mycobacterium tuberculosis largely depends on the secretion of the 6-kD early secreted antigenic target ESAT-6 (EsxA) and the 10-kD culture filtrate protein CFP-10 (EsxB) via the ESX-1/typeVII secretion system. Although gene products from the core RD1 region have been shown to be deeply implicated in this process, less is known about proteins encoded further upstream in the 5' region of the ESX-1 cluster, such as the ESX-1 secretion-associated proteins (Esps) EspF or EspG(1).
  
  
  METHODS
  To elucidate the role of EspF/G(1), whose orthologs in Mycobacterium marinum and Mycobacterium smegmatis are reportedly involved in EsxA/B secretion, we constructed 3 M. tuberculosis knockout strains deleted for espF, espG(1) or the segment corresponding to the combined RD1(bcg)-RD1(mic) region of bacille Calmette-Guérin (BCG) and Mycobacterium microti, which also contains espF and espG(1).
  
  
  RESULTS
  Analysis of these strains revealed that, unlike observations with the model organisms M. smegmatis or M. marinum, disruption of espF and espG(1) in M. tuberculosis did not impact the secretion and T cell recognition of EsxA/B but still caused severe attenuation.
  
  
  CONCLUSIONS
  The separation of the 2 ESX-1-connected phenotypes (ie, EsxA/B secretion and virulence) indicates that EsxA/B secretion is not the only readout for a functional ESX-1 system and suggests that other processes involving EspF/G(1) also play important roles in ESX-1-mediated pathogenicity.
authors.affiliation: Institut Pasteur, UP Pathogénomique Mycobactérienne Intégrée, Paris, France.
authors.forename: Daria
authors.initials: D
authors.lastname: Bottai
authors.forename: Laleh
authors.initials: L
authors.lastname: Majlessi
authors.forename: Roxane
authors.initials: R
authors.lastname: Simeone
authors.forename: Wafa
authors.initials: W
authors.lastname: Frigui
authors.forename: Christine
authors.initials: C
authors.lastname: Laurent
authors.forename: Pascal
authors.initials: P
authors.lastname: Lenormand
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chen
authors.forename: Ida
authors.initials: I
authors.lastname: Rosenkrands
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
authors.forename: Roland
authors.initials: R
authors.lastname: Brosch
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D011499:Protein Processing, Post-Translational; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis