Dataset Information

Infection-driven activation of transglutaminase 2 boosts glucose uptake and hexosamine biosynthesis

ABSTRACT: Transglutaminase 2 (TG2) is a ubiquitous enzyme with transamidating activity. We report here that the expression and activity of TG2 are enhanced in cells infected with the obligate intracellular bacteria Chlamydia trachomatis. Genetic or pharmacological inhibition of TG2 activity impair bacterial development. We show that TG2 increases glucose import by up-regulating the transcription of the glucose transporter genes GLUT-1 and GLUT-3. Furthermore, TG2 activation drives one specific glucose-dependent pathway in the host, i.e. hexosamine biosynthesis. Mechanistically, we identify the glucosamine:fructose-6-phosphate amidotransferase (GFPT) among the substrates of TG2. GFPT modification by TG2 increases its enzymatic activity, resulting in higher levels of UDP-N-acetylglucosamine biosynthesis. As a consequence, TG2 activation results in increased protein O-GlcNAcylation. The correlation between TG2 transamidating activity and O-GlcNAcylation is disrupted in infected cells because host hexosamine biosynthesis is being exploited by the bacteria, in particular to assist their division. In conclusion, our work establishes TG2 as a key player in controlling glucose-derived metabolic pathways in mammalian cells, themselves hijacked by C. trachomatis to sustain their own metabolic needs.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human) Chlamydia Trachomatis E/c599

SUBMITTER: Magalie Duchateau

LAB HEAD: Agathe Subtil

PROVIDER: PXD017117 | Pride | 2020-02-25

REPOSITORIES: Pride

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			Action	DRS
	20151110_MD_Q1_colQ1-12_Laverriere_10.raw	Raw
	20151110_MD_Q1_colQ1-12_Laverriere_11.raw	Raw
	20151110_MD_Q1_colQ1-12_Laverriere_12.raw	Raw
	20151110_MD_Q1_colQ1-12_Laverriere_4.raw	Raw
	20151110_MD_Q1_colQ1-12_Laverriere_5.raw	Raw

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Infection-driven activation of transglutaminase 2 boosts glucose uptake and hexosamine biosynthesis in epithelial cells.

Maffei Benoit B Laverrière Marc M Wu Yongzheng Y Triboulet Sébastien S Perrinet Stéphanie S Duchateau Magalie M Matondo Mariette M Hollis Robert L RL Gourley Charlie C Rupp Jan J Keillor Jeffrey W JW Subtil Agathe A

The EMBO journal 20200305 8

Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme with transamidating activity. We report here that both expression and activity of TG2 are enhanced in mammalian epithelial cells infected with the obligate intracellular bacteria Chlamydia trachomatis. Genetic or pharmacological inhibition of TG2 impairs bacterial development. We show that TG2 increases glucose import by up-regulating the transcription of the glucose transporter genes GLUT-1 and GLUT-3. Furthermore, TG2 activation drive ...[more]

PMID: 32134139

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