title: The FBPase Encoding Gene glpX Is Required for Gluconeogenesis, Bacterial Proliferation and Division In Vivo of Mycobacterium marinum.
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.
authors.affiliation: MOE & MOH Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Tong
authors.affiliation: MOE & MOH Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Institutes of Biomedical Sciences and Institute of Medical Microbiology, Fudan University, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Meng
authors.affiliation: MOE & MOH Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Liu
authors.affiliation: MOE & MOH Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Liangdong
authors.initials: L
authors.lastname: Lyu
authors.affiliation: MOE & MOH Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: MOE & MOH Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: MOE & MOH Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Institutes of Biomedical Sciences and Institute of Medical Microbiology, Fudan University, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: MOE & MOH Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Chen
authors.identifier: http://orcid.org/0000-0001-8251-4336
authors.initials: C
authors.lastname: Niu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002455:Cell Division; D049109:Cell Proliferation; D006597:Fructose-Bisphosphatase / Q000235:genetics* / Q000378:metabolism*; D005943:Gluconeogenesis; D008264:Macrophages / Q000382:microbiology; D009154:Mutation; D019910:Mycobacterium marinum / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015027:Zebrafish / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D006597:Fructose-Bisphosphatase