PUBLICATION
A duplicated ESAT-6 region of ESX-5 is involved in protein export and virulence of mycobacteria
- Authors
- Shah, S., Cannon, J.R., Fenselau, C., Briken, V.
- ID
- ZDB-PUB-150826-4
- Date
- 2015
- Source
- Infection and Immunity 83(11): 4349-61 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Bacterial Proteins/genetics
- Bacterial Proteins/metabolism*
- Bacterial Secretion Systems/genetics
- Bacterial Secretion Systems/metabolism
- Gene Duplication*
- Humans
- Mice
- Mice, Inbred C57BL
- Mycobacterium marinum/genetics
- Mycobacterium marinum/metabolism*
- Mycobacterium marinum/pathogenicity*
- Mycobacterium tuberculosis/genetics
- Mycobacterium tuberculosis/metabolism
- Mycobacterium tuberculosis/pathogenicity
- Protein Transport
- Tuberculosis/microbiology*
- Virulence
- PubMed
- 26303392 Full text @ Infect. Immun.
Citation
Shah, S., Cannon, J.R., Fenselau, C., Briken, V. (2015) A duplicated ESAT-6 region of ESX-5 is involved in protein export and virulence of mycobacteria. Infection and Immunity. 83(11):4349-61.
Abstract
The ESX-5 secretion system of Mycobacterium tuberculosis (Mtb) is important for bacterial virulence and the secretion of the large PE/PPE protein family that constitutes 10% of the Mtb genome. A four-gene region of ESX-5 is duplicated three times in the Mtb genome but the function of these duplicates is unknown. Here we investigated one of these duplicates, the esxI, esxJ, ppe15 and pe8 (ESX-5a) region. ESX-5a deletion mutant in the model system, M. marinum (Mm) background was deficient in the secretion of some members of the PE/PPE family of proteins. Surprisingly, we also identified other proteins that are not members this family, thus expanding the range ESX-5 secretion substrates. In addition, we demonstrate that ESX-5a is important for virulence of Mm in the zebrafish model. Furthermore, we show the role of the Mtb ESX-5a region in inflammasome activation but not in host cell death induction, which is different from the Mtb ESX-5 system. In conclusion, the ESX-5a region is non-redundant with its ESX-5 paralog and is necessary for secretion of a specific subset of proteins in Mtb and Mm that are important for bacterial virulence of Mm. Our findings point to a role for the three ESX-5 duplicate regions in the selection of substrates for secretion via ESX-5 and hence they provide the basis for a refined model of the molecular mechanism of this type VII secretion system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping