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- W2745930292 endingPage "e1006978" @default.
- W2745930292 startingPage "e1006978" @default.
- W2745930292 abstract "To achieve robust replication, bacteria must integrate cellular metabolism and cell wall growth. While these two processes have been well characterized, the nature and extent of cross-regulation between them is not well understood. Here, using classical genetics, CRISPRi, metabolomics, transcriptomics and chemical complementation approaches, we show that a loss of the master regulator Hfq in Caulobacter crescentus alters central metabolism and results in cell shape defects in a nutrient-dependent manner. We demonstrate that the cell morphology phenotype in the hfq deletion mutant is attributable to a disruption of α-ketoglutarate (KG) homeostasis. In addition to serving as a key intermediate of the tricarboxylic acid (TCA) cycle, KG is a by-product of an enzymatic reaction required for the synthesis of peptidoglycan, a major component of the bacterial cell wall. Accumulation of KG in the hfq deletion mutant interferes with peptidoglycan synthesis, resulting in cell morphology defects and increased susceptibility to peptidoglycan-targeting antibiotics. This work thus reveals a direct crosstalk between the TCA cycle and cell wall morphogenesis. This crosstalk highlights the importance of metabolic homeostasis in not only ensuring adequate availability of biosynthetic precursors, but also in preventing interference with cellular processes in which these intermediates arise as by-products." @default.
- W2745930292 created "2017-08-31" @default.
- W2745930292 creator A5009377788 @default.
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- W2745930292 creator A5051991967 @default.
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- W2745930292 date "2017-08-21" @default.
- W2745930292 modified "2023-10-14" @default.
- W2745930292 title "Crosstalk between the tricarboxylic acid cycle and peptidoglycan synthesis in Caulobacter crescentus through the homeostatic control of α-ketoglutarate" @default.
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- W2745930292 doi "https://doi.org/10.1371/journal.pgen.1006978" @default.
- W2745930292 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5578688" @default.
- W2745930292 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28827812" @default.
- W2745930292 hasPublicationYear "2017" @default.
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