PUBLICATION
The ESX-5 System of Pathogenic Mycobacteria Is Involved In Capsule Integrity and Virulence through Its Substrate PPE10
- Authors
- Ates, L.S., van der Woude, A.D., Bestebroer, J., van Stempvoort, G., Musters, R.J., Garcia-Vallejo, J.J., Picavet, D.I., Weerd, R.V., Maletta, M., Kuijl, C.P., van der Wel, N.N., Bitter, W.
- ID
- ZDB-PUB-160610-3
- Date
- 2016
- Source
- PLoS pathogens 12: e1005696 (Journal)
- Registered Authors
- Bitter, Wilbert
- Keywords
- Mycobacterium tuberculosis, Flow cytometry, Detergents, Embryos, Zebrafish, Secretion, Transposable elements, Complement system
- MeSH Terms
-
- Flow Cytometry
- Chromatography, Thin Layer
- Virulence/physiology*
- Disease Models, Animal
- Zebrafish
- Type VII Secretion Systems/metabolism*
- Microscopy, Electron
- Humans
- Bacterial Capsules/metabolism*
- Mycobacterium marinum/metabolism
- Mycobacterium marinum/pathogenicity*
- Virulence Factors/metabolism
- Mycobacterium Infections, Nontuberculous/metabolism*
- Immunoblotting
- Animals
- Cell Line
- PubMed
- 27280885 Full text @ PLoS Pathog.
Citation
Ates, L.S., van der Woude, A.D., Bestebroer, J., van Stempvoort, G., Musters, R.J., Garcia-Vallejo, J.J., Picavet, D.I., Weerd, R.V., Maletta, M., Kuijl, C.P., van der Wel, N.N., Bitter, W. (2016) The ESX-5 System of Pathogenic Mycobacteria Is Involved In Capsule Integrity and Virulence through Its Substrate PPE10. PLoS pathogens. 12:e1005696.
Abstract
Mycobacteria produce a capsule layer, which consists of glycan-like polysaccharides and a number of specific proteins. In this study, we show that, in slow-growing mycobacteria, the type VII secretion system ESX-5 plays a major role in the integrity and stability of the capsule. We have identified PPE10 as the ESX-5 substrate responsible for this effect. Mutants in esx-5 and ppe10 both have impaired capsule integrity as well as reduced surface hydrophobicity. Electron microscopy, immunoblot and flow cytometry analyses demonstrated reduced amounts of surface localized proteins and glycolipids, and morphological differences in the capsular layer. Since capsular proteins secreted by the ESX-1 system are important virulence factors, we tested the effect of the mutations that cause capsular defects on virulence mechanisms. Both esx-5 and ppe10 mutants of Mycobacterium marinum were shown to be impaired in ESX-1-dependent hemolysis. In agreement with this, the ppe10 and esx5 mutants showed reduced recruitment of ubiquitin in early macrophage infection and intermediate attenuation in zebrafish embryos. These results provide a pivotal role for the ESX-5 secretion system and its substrate PPE10, in the capsular integrity of pathogenic mycobacteria. These findings open up new roads for research on the mycobacterial capsule and its role in virulence and immune modulation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping