The ESX-5 System of Pathogenic Mycobacteria Is Involved In Capsule Integrity and Virulence through Its Substrate PPE10

PLoS Pathogens

Robert van de Weerd¹  Wilbert Bitter¹  Aniek D. van der Woude²  Nicole N. van der Wel²  Massimiliano Maletta²  Louis S. Ates²  Gunny van Stempvoort²  Daisy I. Picavet³  Jovanka Bestebroer⁴  René J. P. Musters⁴  Juan J. Garcia-Vallejo⁵  Coenraad P. Kuijl⁶ 

[1] Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam the Netherlands;Department of Medical Microbiology and Infection Prevention, VU University Medical Center, Amsterdam, the Netherlands;Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands;Department of Molecular Microbiology, VU University, Amsterdam, the Netherlands;Department of Physiology and Cardiology, VU University Medical Center, Amsterdam, the Netherlands;Eyen SE, Prague, Czech Republic

关键词: Mycobacterium tuberculosis;    Flow cytometry;    Detergents;    Embryos;    Zebrafish;    Secretion;    Transposable elements;    Secretion systems;   

DOI  :  10.1371/journal.ppat.1005696

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY