PUBLICATION
Inorganic phosphate limitation modulates capsular polysaccharide composition in mycobacteria
- Authors
- van de Weerd, R., Boot, M., Maaskant, J., Sparrius, M., Verboom, T., van Leeuwen, L.M., Burggraaf, M.J., Paauw, N.J., Dainese, E., Manganelli, R., Bitter, W., Appelmelk, B.J., Geurtsen, J.
- ID
- ZDB-PUB-160406-9
- Date
- 2016
- Source
- The Journal of biological chemistry 291(22): 11787-99 (Journal)
- Registered Authors
- Appelmelk, Ben J., Bitter, Wilbert
- Keywords
- Mycobacterium tuberculosis, cell surface, confocal microscopy, electron microscopy (EM), zebrafish
- MeSH Terms
-
- Animals
- Bacterial Capsules/drug effects
- Bacterial Capsules/metabolism*
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism*
- Embryo, Nonmammalian/microbiology
- Mycobacterium Infections, Nontuberculous/drug therapy*
- Mycobacterium Infections, Nontuberculous/microbiology
- Mycobacterium marinum/drug effects*
- Phosphates/pharmacology*
- Polysaccharides/metabolism*
- Zebrafish
- PubMed
- 27044743 Full text @ J. Biol. Chem.
Citation
van de Weerd, R., Boot, M., Maaskant, J., Sparrius, M., Verboom, T., van Leeuwen, L.M., Burggraaf, M.J., Paauw, N.J., Dainese, E., Manganelli, R., Bitter, W., Appelmelk, B.J., Geurtsen, J. (2016) Inorganic phosphate limitation modulates capsular polysaccharide composition in mycobacteria. The Journal of biological chemistry. 291(22):11787-99.
Abstract
Mycobacterium tuberculosis is protected by an unusual and highly impermeable cell-envelope that is critically important for the successful colonisation of the host. The outermost surface of this cell envelope is formed by capsular polysaccharides that play an important role in modulating the initial interactions once the bacillus enters the body. Although the bio-enzymatic steps involved in the production of the capsular polysaccharides are emerging, information regarding the ability of the bacterium to modulate the composition of the capsule is still unknown. Here, we study the mechanisms involved in regulation of mycobacterial capsule biosynthesis using a high throughput screen for gene products involved in capsular α-glucan production. Utilizing this approach we identified a group of mutants that all carried mutations in the ABC phosphate transport locus pst. These mutants collectively exhibited a strong overproduction of capsular polysaccharides, including α -glucan and arabinomannan, suggestive of a role for inorganic phosphate (Pi) metabolism in modulating capsular polysaccharide production. These findings were corroborated by the observation that growth under low Pi conditions as well as chemical activation of the stringent response induces capsule production in a number of mycobacterial species. This induction is, in part, dependent on sigma factor E. Finally, we show that M. marinum, a model organism for M. tuberculosis, encounters Pi-stress during infection, which shows the relevance of our findings in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping