PXD010498-1

PXD010498 is an original dataset announced via ProteomeXchange.

Title	Metabolic reprogramming with the induction of toxin production of Clostridioides difficile during the stationary phase
Description	The obligate anaerobe, spore forming bacterium Clostridioides difficile (formerly Clostridium difficile) causes nosocomial and community acquired diarrhea often associated with antibiotic therapy. Major virulence factors of the bacterium are the two large clostridial toxins TcdA and TcdB. The production of both toxins was found strongly connected to the metabolism as well as the nutritional status in the environment. Here, we systematically investigated the changes of the gene regulatory, proteomic and metabolic networks of C. difficile 630Δerm underlying the adaptation to the non-growing state in the stationary phase. Integrated data from time-resolved transcriptome, proteome and metabolome investigations performed under defined growth conditions uncovered multiple adaptation strategies. Overall changes in the cellular processes included the downregulation of ribosome production, lipid metabolism, cold shock proteins, spermine biosynthesis, and glycolysis and in the later stages of riboflavin and coenzyme A biosynthesis. In contrast, several fermentation pathways, different chaperones and the cysteine, serine and pantothenate biosynthesis were upregulated. Focused on the Stickland amino acid fermentation and the central carbon metabolism, we demonstrated the ability of C. difficile to replenish its favored amino acid cysteine by a pathway from the glycolysis substrate 3-phosphoglycerate via L-serine. Following the growth course, the reductive equivalent pathways used were sequentially shifted from proline via leucine/phenylalanine to the central carbon metabolism first using butanoate fermentation and then to lactate. The toxin production was found correlated mainly to fluxes of the central carbon metabolism. Toxin formation in the supernatant was detected when the flux changed from butanoate to lactate synthesis in the late stationary phase. The holistic view derived from the combination of transcriptome, proteome and metabolome data allowed us to uncover the major metabolic strategies that are used by the clostridial cells to maintain its cellular integrity and ensure survival under starvation conditions.
HostingRepository	PRIDE
AnnounceDate	2018-09-13
AnnouncementXML	Submission_2018-09-13_00:19:25.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Otto
SpeciesList	scientific name: Peptoclostridium difficile (strain 630) (Clostridium difficile); NCBI TaxID: 272563;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-19 04:17:27	ID requested
⏵ 1	2018-09-13 00:19:27	announced

Hofmann JD, Otto A, Berges M, Biedendieck R, Michel AM, Becher D, Jahn D, Neumann-Schaal M, During the Stationary Phase With the Induction of Toxin Production. Front Microbiol, 9():1970(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Clostridium difficile, Clostridioides difficile, metabolism, toxin formation, starvation, Stickland reactions

Prof. Dr. Dörte Becher
contact affiliation	Institut für Mikrobiologie Dept. Mikrobielle Proteomik Universität Greifswald Felix-Hausdorff-Str. 8 17489 Greifswald
contact email	dbecher@uni-greifswald.de
lab head
Andreas Otto
contact affiliation	Institute for Microbiology
contact email	andreas.otto@uni-greifswald.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/09/PXD010498

PRIDE project URI

• PRIDE
  1. PXD010498
     1. Label: PRIDE project
     2. Name: Metabolic reprogramming with the induction of toxin production of Clostridioides difficile during the stationary phase