Acetylation coordinates the crosstalk between carbon metabolism and ammonium assimilation in Salmonella enterica

Enteric bacteria use up to 15% of their cellular energy for ammonium assimilation via glutamine synthetase (GS)/glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH) in response to varying ammonium availability. However, the sensory mechanisms for effective and appropriate coordination betwee...

Full description

Saved in:

Bibliographic Details
Published in:	The EMBO journal 2023-07, Vol.42 (13), p.e112333-n/a
Main Authors:	Sun, Yunwei, Zhang, Yuebin, Zhao, Tingting, Luan, Yi, Wang, Ying, Yang, Chen, Shen, Bo, Huang, Xi, Li, Guohui, Zhao, Shimin, Zhao, Guo‐ping, Wang, Qijun
Format:	Article
Language:	eng
Subjects:	Acetylation Acetyltransferase Ammonium ammonium assimilation Ammonium Compounds - metabolism Animals Assimilation Availability Bacteria Carbon Carbon - metabolism coordination Deacetylation Deactivation Dehydrogenase Dehydrogenases Enzymes Glucose Glucose metabolism Glutamate dehydrogenase Glutamate Dehydrogenase - metabolism Glutamate-ammonia ligase Glutamine Lysine Metabolism Mice Mimicry Molecular dynamics Mutation Nitrogen - metabolism Salmonella Salmonella enterica Synthesis Virulence
Online Access:	Request full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Enteric bacteria use up to 15% of their cellular energy for ammonium assimilation via glutamine synthetase (GS)/glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH) in response to varying ammonium availability. However, the sensory mechanisms for effective and appropriate coordination between carbon metabolism and ammonium assimilation have not been fully elucidated. Here, we report that in Salmonella enterica, carbon metabolism coordinates the activities of GS/GDH via functionally reversible protein lysine acetylation. Glucose promotes Pat acetyltransferase‐mediated acetylation and activation of adenylylated GS. Simultaneously, glucose induces GDH acetylation to inactivate the enzyme by impeding its catalytic centre, which is reversed upon GDH deacetylation by deacetylase CobB. Molecular dynamics (MD) simulations indicate that adenylylation is required for acetylation‐dependent activation of GS. We show that acetylation and deacetylation occur within minutes of “glucose shock” to promptly adapt to ammonium/carbon variation and finely balance glutamine/glutamate synthesis. Finally, in a mouse infection model, reduced S. enterica growth caused by the expression of adenylylation‐mimetic GS is rescued by acetylation‐mimicking mutations. Thus, glucose‐driven acetylation integrates signals from ammonium assimilation and carbon metabolism to fine‐tune bacterial growth control. Synopsis In Salmonella enterica, metabolic enzyme acetylation regulates carbon metabolism. Here, glucose availability is shown to regulate ammonium assimilation and virulence in Salmonella. Acetylation of glutamine synthetase (GS) and glutamate dehydrogenase (GDH) is regulated by acetyltransferase Pat and deacetylase CobB. Glucose promotes acetylation to activate adenylylated GS and inactivate GDH by impeding its catalytic centre. Acetylation of GS and GDH occurs within minutes to adapt to the ammonium/carbon variation and balance glutamate/glutamine synthesis. GS acetylation‐mimicking mutations enhance Salmonella survival in infected mice. Glucose regulates acetylation of glutamate and glutamine biosynthesis enzymes to enhance bacterial survival in infected mice.
ISSN:	0261-4189 1460-2075