title: A unique Mycobacterium ESX-1 protein co-secretes with CFP-10/ESAT-6 and is necessary for inhibiting phagosome maturation.
abstract: The ESX-1 secretion system plays a critical role in the virulence of Mycobacterium tuberculosis and M. marinum. To date, three proteins are known to be secreted by ESX-1 and necessary for virulence, two of which are CFP-10 and ESAT-6. The ESX-1 secretion and the virulence mechanisms are not well understood. In this study, we have examined the M. marinum secretomes and identified four proteins specific to ESX-1. Two of those are CFP-10 and ESAT-6, and the other two are novel: MM1553 (homologous to Rv3483c) and Mh3881c (homologous to Rv3881c). We have shown that Mh3881c, CFP-10 and ESAT-6 are co-dependent for secretion. Mh3881c is being cleaved at close to the C-terminus during secretion, and the C-terminal portion is critical to the co-dependent secretion, the ESAT-6 cellular levels, and interaction with ESAT-6. The co-dependent secretion is required for M. marinum intracellular growth in macrophages, where the Mh3881c C-terminal portion plays a critical role. The role of the co-dependent secretion in intracellular growth correlates with its role in inhibiting phagosome maturation. Both the secretion and the virulence defects of the Mh3881c mutant are complemented by Mh3881c or its M. tuberculosis homologue Rv3881c, suggesting that in M. tuberculosis, Rv3881c has similar functions.
authors: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors: Junjie
authors: J
authors: Xu
authors: Olli
authors: O
authors: Laine
authors: Mark
authors: M
authors: Masciocchi
authors: Joanna
authors: J
authors: Manoranjan
authors: Jennifer
authors: J
authors: Smith
authors: Shao Jun
authors: SJ
authors: Du
authors: Nathan
authors: N
authors: Edwards
authors: Xiaoping
authors: X
authors: Zhu
authors: Catherine
authors: C
authors: Fenselau
authors: Lian-Yong
authors: LY
authors: Gao
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D013058:Mass Spectrometry; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000378:metabolism* / Q000472:pathogenicity; D010588:Phagosomes / Q000378:metabolism*; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis