Dataset Information

Polarly Localized EccE1 Is Required for ESX-1 Function and Stabilization of ESX-1 Membrane Proteins in Mycobacterium tuberculosis.

ABSTRACT: Mycobacterium tuberculosis is a slow-growing intracellular bacterium with the ability to induce host cell death and persist indefinitely in the human body. This pathogen uses the specialized ESX-1 secretion system to secrete virulence factors and potent immunogenic effectors required for disease progression. ESX-1 is a multisubunit apparatus with a membrane complex that is predicted to form a channel in the cytoplasmic membrane. In M. tuberculosis this complex is composed of five membrane proteins: EccB1, EccCa1, EccCb1, EccD1, and EccE1 In this study, we have characterized the membrane component EccE1 and found that deletion of eccE 1 lowers the levels of EccB1, EccCa1, and EccD1, thereby abolishing ESX-1 secretion and attenuating M. tuberculosis ex vivo Surprisingly, secretion of EspB was not affected by loss of EccE1 Furthermore, EccE1 was found to be a membrane- and cell wall-associated protein that needs the presence of other ESX-1 components to assemble into a stable complex at the poles of M. tuberculosis Overall, this investigation provides new insights into the role of EccE1 and its localization in M. tuberculosis IMPORTANCE Tuberculosis (TB), the world's leading cause of death of humans from an infectious disease, is caused by the intracellular bacterium Mycobacterium tuberculosis The development of successful strategies to control TB requires better understanding of the complex interactions between the pathogen and the human host. We investigated the contribution of EccE1, a membrane protein, to the function of the ESX-1 secretion system, the major virulence determinant of M. tuberculosis By combining genetic analysis of selected mutants with eukaryotic cell biology and proteomics, we demonstrate that EccE1 is critical for ESX-1 function, secretion of effector proteins, and pathogenesis. Our research improves knowledge of the molecular basis of M. tuberculosis virulence and enhances our understanding of pathogenesis.

SUBMITTER: Soler-Arnedo P

PROVIDER: S-EPMC7015709 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Polarly Localized EccE1 Is Required for ESX-1 Function and Stabilization of ESX-1 Membrane Proteins in Mycobacterium tuberculosis.

Soler-Arnedo Paloma P Sala Claudia C Zhang Ming M Cole Stewart T ST Piton Jérémie J

Journal of bacteriology 20200211 5

Mycobacterium tuberculosis is a slow-growing intracellular bacterium with the ability to induce host cell death and persist indefinitely in the human body. This pathogen uses the specialized ESX-1 secretion system to secrete virulence factors and potent immunogenic effectors required for disease progression. ESX-1 is a multisubunit apparatus with a membrane complex that is predicted to form a channel in the cytoplasmic membrane. In M. tuberculosis this complex is composed of five m ...[more]

PMID: 31843799

Similar Datasets

Project description:Pathogenic mycobacteria contain up to five type VII secretion (T7S) systems, ESX-1 to ESX-5. One of the conserved T7S components is the serine protease mycosin (MycP). Strikingly, whereas MycP is essential for secretion, the protease activity of MycP1 in Mycobacterium tuberculosis has been shown to be dispensable for secretion. The essential role of MycP therefore remains unclear. Here we show that MycP1 and MycP5 of M. marinum have similar phenotypes, confirming that MycP has a second unknown function that is essential for its T7S system. To investigate whether this role is related to proper functioning of the T7S membrane complex, we first analyzed the composition of the ESX-1 membrane complex and showed that this complex consists of EccBCDE1, similarly to what was previously shown for ESX-5. Surprisingly, while mycosins are not an integral part of these purified core complexes, we noticed that the stability of both the ESX-1 complex and the ESX-5 complex is compromised in the absence of their MycP subunit. Additional interaction studies showed that, although mycosins are not part of the central ESX membrane complex, they loosely associate with this complex. We hypothesize that this MycP association with the core membrane complex is crucial for the integrity and functioning of the T7S machinery. Among the major virulence factors of pathogenic mycobacteria are the type VII secretion (T7S) systems. Three of these systems, ESX-1, ESX-3, and ESX-5, have been shown to be crucial for virulence or viability. Here we describe the function of mycosin proteases, which are conserved components within these systems. We show that MycP1 and MycP5 have a second, proteolytic-independent function which is essential for the T7S system. We additionally found that this second essential role is related to the stabilization and proper functioning of their respective ESX membrane core complexes. Finally, we found that this is mediated by a loose association of MycP with the complex. Understanding the essential role of mycosins in type VII secretion systems, which play central roles in the virulence and viability of pathogenic mycobacteria, may provide new intervention strategies to treat tuberculosis.

Dataset Information

Polarly Localized EccE1 Is Required for ESX-1 Function and Stabilization of ESX-1 Membrane Proteins in Mycobacterium tuberculosis.

Publications

Polarly Localized EccE<sub>1</sub> Is Required for ESX-1 Function and Stabilization of ESX-1 Membrane Proteins in Mycobacterium tuberculosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets