Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase.

Détails

Ressource 1Télécharger: BIB_0915D7CA0396.P001.pdf (1702.75 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_0915D7CA0396
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase.
Périodique
mBio
Auteur(s)
Gonzalez D., Collier J.
ISSN
2150-7511 (Electronic)
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
6
Numéro
4
Pages
e00952
Langue
anglais
Résumé
UNLABELLED: CcrM is an orphan DNA methyltransferase nearly universally conserved in a vast group of Alphaproteobacteria. In Caulobacter crescentus, it controls the expression of key genes involved in the regulation of the cell cycle and cell division. Here, we demonstrate, using an experimental evolution approach, that C. crescentus can significantly compensate, through easily accessible genetic changes like point mutations, the severe loss in fitness due to the absence of CcrM, quickly improving its growth rate and cell morphology in rich medium. By analyzing the compensatory mutations genome-wide in 12 clones sampled from independent ΔccrM populations evolved for ~300 generations, we demonstrated that each of the twelve clones carried at least one mutation that potentially stimulated ftsZ expression, suggesting that the low intracellular levels of FtsZ are the major burden of ΔccrM mutants. In addition, we demonstrate that the phosphoenolpyruvate-carbohydrate phosphotransfer system (PTS) actually modulates ftsZ and mipZ transcription, uncovering a previously unsuspected link between metabolic regulation and cell division in Alphaproteobacteria. We present evidence that point mutations found in genes encoding proteins of the PTS provide the strongest fitness advantage to ΔccrM cells cultivated in rich medium despite being disadvantageous in minimal medium. This environmental sign epistasis might prevent such mutations from getting fixed under changing natural conditions, adding a plausible explanation for the broad conservation of CcrM.
IMPORTANCE: In bacteria, DNA methylation has a variety of functions, including the control of DNA replication and/or gene expression. The cell cycle-regulated DNA methyltransferase CcrM modulates the transcription of many genes and is critical for fitness in Caulobacter crescentus. Here, we used an original experimental evolution approach to determine which of its many targets make CcrM so important physiologically. We show that populations lacking CcrM evolve quickly, accumulating an excess of mutations affecting, directly or indirectly, the expression of the ftsZ cell division gene. This finding suggests that the most critical function of CcrM in C. crescentus is to promote cell division by enhancing FtsZ intracellular levels. During this work, we also discovered an unexpected link between metabolic regulation and cell division that might extend to other Alphaproteobacteria.
Mots-clé
Adaptation, Biological, Bacterial Proteins/genetics, Bacterial Proteins/metabolism, Caulobacter crescentus/enzymology, Caulobacter crescentus/genetics, Cell Division, Culture Media/chemistry, Cytoskeletal Proteins/genetics, Cytoskeletal Proteins/metabolism, DNA Mutational Analysis, DNA, Bacterial/chemistry, DNA, Bacterial/genetics, Gene Deletion, Genome, Bacterial, Methyltransferases/deficiency, Phosphoenolpyruvate Sugar Phosphotransferase System/genetics, Phosphoenolpyruvate Sugar Phosphotransferase System/metabolism, Suppression, Genetic
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/06/2015 8:56
Dernière modification de la notice
20/08/2019 12:31
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