PUBLICATION

The FBPase Encoding Gene glpX Is Required for Gluconeogenesis, Bacterial Proliferation and Division In Vivo of Mycobacterium marinum

Authors
Tong, J., Meng, L., Wang, X., Liu, L., Lyu, L., Wang, C., Li, Y., Gao, Q., Yang, C., Niu, C.
ID
ZDB-PUB-160528-1
Date
2016
Source
PLoS One   11: e0156663 (Journal)
Registered Authors
Li, Yang
Keywords
Mycobacterium tuberculosis, Zebrafish, Macrophages, Cell cycle and cell division, Glycerol, Intracellular pathogens, Glucose, Larvae
MeSH Terms
  • Animals
  • Anti-Bacterial Agents/pharmacology
  • Cell Division*
  • Cell Proliferation
  • Fructose-Bisphosphatase/genetics*
  • Fructose-Bisphosphatase/metabolism*
  • Gluconeogenesis*
  • Macrophages/microbiology
  • Mutation
  • Mycobacterium marinum/cytology*
  • Mycobacterium marinum/drug effects
  • Mycobacterium marinum/enzymology
  • Mycobacterium marinum/metabolism*
  • Zebrafish/microbiology
PubMed
27233038 Full text @ PLoS One
Abstract
Lipids have been identified as important carbon sources for Mycobacterium tuberculosis (Mtb) to utilize in vivo. Thus gluconeogenesis bears a key role for Mtb to survive and replicate in host. A rate-limiting enzyme of gluconeogenesis, fructose 1, 6-bisphosphatase (FBPase) is encoded by the gene glpX. The functions of glpX were studied in M. marinum, a closely related species to Mtb. The glpX deletion strain (ΔglpX) displayed altered gluconeogenesis, attenuated virulence, and altered bacterial proliferation. Metabolic profiles indicate an accumulation of the FBPase substrate, fructose 1, 6-bisphosphate (FBP) and altered gluconeogenic flux when ΔglpX is cultivated in a gluconeogenic carbon substrate, acetate. In both macrophages and zebrafish, the proliferation of ΔglpX was halted, resulting in dramatically attenuated virulence. Intracellular ΔglpX exhibited an elongated morphology, which was also observed when ΔglpX was grown in a gluconeogenic carbon source. This elongated morphology is also supported by the observation of unseparated multi-nucleoid cell, indicating that a complete mycobacterial division in vivo is correlated with intact gluconeogenesis. Together, our results indicate that glpX has essential functions in gluconeogenesis, and plays an indispensable role in bacterial proliferation in vivo and virulence of M. marinum.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping