PXD040738-2

PXD040738 is an original dataset announced via ProteomeXchange.

Title	Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach
Description	A major risk factor for Clostridioides difficile infection (CDI) is the perturbation of the gut microbiota by antibiotic administration, and antibiotic therapy, the standard treatment option for CDI, exacerbates the imbalance of the gut microbiota, leading to a very high recurrent CDI (rCDI) incidence rate. Therefore, CDI treatment based on live biotherapeutic products (LBPs) has recently emerged for long-term CDI management and preventive treatment However, there is limited research and understanding of how these LBPs improve CDI symptoms, which raises the need to elucidate the therapeutic mechanisms of LBPs. To fill this knowledge gap, here, we holistically analyzed and investigated the mechanisms involved in the inhibitory effect of probiotics on C. difficile at the molecular level through a multiomics approach on screened strain from probiotics that inhibit C. difficile growth. First, Bifidobacterium species were co-cultured with C. difficile, and B. longum was screened based on its ability to inhibit the growth of C. difficile. Then, the antimicrobial activity of B. longum against C. difficile was confirmed by spot-on-lawn assay and organic acid quantification. Next, we performed proteomic and metabolomic analysis on C. difficile co-cultured with B. longum, and observed physiological changes associated with the inhibition of C. difficile growth and toxin production. It was found that lactate produced by B. longum up-regulated the lactate dehydrogenase complex of C. difficile, leading to a decrease in intracellular ATP synthesis and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Furthermore, proteinaceous stress induced by B. longum was also identified through the up-regulation of ribosomal proteins, molecular chaperones, and chaperonins, and the down-regulation of translation-related proteins. Finally, we found that B. longum suppressed butyrate metabolism and toxin production by producing and replenishing proline consumed by C. difficile. Therefore, this study will not only expand our understanding of the mechanisms of probiotics' inhibition of C. difficile, but also contribute to the development of LBPs based on molecular mechanisms for treating CDI.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:25:37.350.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sung-Hyun Jo
SpeciesList	scientific name: Clostridioides difficile ATCC 9689 = DSM 1296; NCBI TaxID: 1121308;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-09 15:53:18	ID requested
1	2024-01-26 06:50:51	announced
⏵ 2	2024-10-22 06:25:39	announced	2024-10-22: Updated project metadata.

10.3389/fmicb.2023.1293149;

Jo SH, Jeon HJ, Song WS, Lee JS, Kwon JE, Park JH, Kim YR, Kim MG, Baek JH, Kwon SY, Kim JS, Yang YH, Kim YG, multiomics approach. Front Microbiol, 14():1293149(2023) [pubmed]

submitter keyword: Metabolomics, Microbe-microbe interaction,Clostridioides difficile, Molecular mechanism., Bifidobacterium longum, Proteomics

Yun-Gon Kim
contact affiliation	Department of Chemical Engineering, Laboratory of Cellular and Biomolecular Engineering, Soongsil University, Republic of Korea
contact email	ygkim@ssu.ac.kr
lab head
Sung-Hyun Jo
contact affiliation	Soongsil university
contact email	sh20511@soongsil.ac.kr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040738
     1. Label: PRIDE project
     2. Name: Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach