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PPE and PE_PGRS proteins of Mycobacterium marinum are transported via the type VII secretion system ESX-5 |
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| Authors: | Abdallah M Abdallah Theo Verboom Eveline M Weerdenburg Nicolaas C Gey van Pittius Phetole W Mahasha Connie Jiménez Marcela Parra Nathalie Cadieux Michael J Brennan Ben J Appelmelk Wilbert Bitter |
| Institution: | Department of Medical Microbiology and Infection Control, and;OncoProteomics Laboratory, Vumc Cancer Centre Amsterdam, VU University Medical Centre, Amsterdam, the Netherlands.; DST/NRF Centre of Excellence for Biomedical TB Research/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences –Stellenbosch University, PO Box 19063, Tygerberg 7505, South Africa.; Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. |
| Abstract: | ESX-5 is one of the five type VII secretion systems found in mycobacteria. These secretion systems are also known as ESAT-6-like secretion systems. Here, we have determined the secretome of ESX-5 by a proteomic approach in two different strains of Mycobacterium marinum . Comparison of the secretion profile of wild-type strains and their ESX-5 mutants showed that a number of PE_PGRS and PPE-MPTR proteins are dependent on ESX-5 for transport. The PE and PPE protein families are unique to mycobacteria, are highly expanded in several pathogenic species, such as Mycobacterium tuberculosis and M. marinum , and certain family members are cell surface antigens associated with virulence. Using a monoclonal antibody directed against the PGRS domain we showed that nearly all PE_PGRS proteins that are recognized by this antibody are missing in the supernatant of ESX-5 mutants. In addition to PE_PGRS and PPE proteins, the ESX-5 secretion system is responsible for the secretion of a ESAT-6-like proteins. Together, these data show that ESX-5 is probably a major secretion pathway for mycobacteria and that this system is responsible for the secretion of recently evolved PE_PGRS and PPE proteins. |
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