A Mycobacterium ESX-1–Secreted Virulence Factor with Unique Requirements for Export

• DOI: 10.1371/journal.ppat.0030105
• Publication Date: 2007-07-27T19:43:21Z
• Authors: Bryant McLaughlin; Janet S Chon; Jason A MacGurn; Fredric Carlsson; Terri L Cheng; Jeffery S Cox; Eric J Brown
• Keywords: Mycobacterium marinum; ESAT-6; Secretory protein; Virulence factor

Specialized secretion systems of pathogenic bacteria commonly transport multiple effectors that act in concert to control and exploit the host cell as a replication-permissive niche. Both Mycobacterium marinum tuberculosis genomes contain an extended region difference 1 (extRD1) locus encodes one such pathway, early secretory antigenic target 6 (ESAT-6) system (ESX-1) apparatus. ESX-1 is required for virulence proteins ESAT-6, culture filtrate protein 10 (CFP-10), EspA. Here, we show both Rv3881c its M. homolog, Mh3881c, are secreted proteins, disruption RD1 either organism blocks secretion. We have renamed Rv3881c/Mh3881c gene espB substrate B. Secretion EspB (EspBM) requires Mh3879c Mh3871 genes within RD1, while CFP-10 not affected by Mh3879c. In contrast, Mh3866 or Mh3867 extRD1 prevents without effect on EspBM. Mutants fail secrete only EspBM less attenuated macrophages than mutants failing substrates. physically interacts with Mh3879c; EspBT, Rv3879c; bind be secreted. also found interaction between Rv3879c Rv3871, component machine, suggesting mechanism EspB. The results establish growth suggests contribution may arise from independent