PXD054316

PXD054316 is an original dataset announced via ProteomeXchange.

Title	Acquisition of mecA confers resistance to inhibition of Clostridioides difficile sporulation by cephamycins.
Description	The spread of antibiotic resistance is a growing global challenge that is estimated to be directly responsible for around 1.3 million deaths each year worldwide. Certain groups of bacteria produce spores, a hardy cell form whose persistence and transmission properties have been implicated in the spread of antibiotic resistance genes 1,2. However, the interplay between antibiotic resistance genes and spore biology is poorly understood. Spores of the human and animal pathogen Clostridioides difficile are a crucial driver of disease dissemination, initiation, and re-infection. We previously showed that cephamycin antibiotics can inhibit spore formation in C. difficile epidemic isolates by targeting the spore-specific penicillin binding protein CdSpoVD 3. Here, we show that acquisition of a penicillin binding protein, CdMecA, by C. difficile strains blocks spore inhibition by cephamycins, uncovering a unique mode of antibiotic resistance. CdMecA is prevalent in 9.8% of 10,000 C. difficile genomes surveyed and can be found amongst both gut and environmental bacterial spore-formers. Spore resilience and germination studies revealed differences in phenotypic properties between wild-type CdSpoVD spores and cephamycin-induced CdMecA spores. The fifth-generation cephalosporin, ceftobiprole, can target CdMecA, and in combination with the cephamycin cefotetan restored inhibition of spore formation. Our work shows for the first time how an acquired antibiotic resistance gene can unexpectedly, and directly, modulate spore formation, highlighting the detrimental impact of antibiotic overuse in healthcare and animal production environments.
HostingRepository	PRIDE
AnnounceDate	2026-06-03
AnnouncementXML	Submission_2026-06-02_19:20:11.731.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ghizal Siddiqui
SpeciesList	scientific name: Peptoclostridium difficile (strain 630) (Clostridium difficile); NCBI TaxID: NEWT:272563; scientific name: Bacteria; NCBI TaxID: NCBITaxon:2;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-28 22:31:17	ID requested
⏵ 1	2026-06-02 19:20:12	announced

Dataset with its publication pending

submitter keyword: penicillin binding proteins, MecA, sporulation,Clostridioides difficile, spore-forming bacteria, antibiotic resistance, Clostridium difficile

Darren Creek
contact affiliation	Drug, Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia
contact email	darren.creek@monash.edu
lab head
Ghizal Siddiqui
contact affiliation	Monash University
contact email	ghizal.siddiqui@monash.edu
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/2026/06/PXD054316

PRIDE project URI

• PRIDE
  1. PXD054316
     1. Label: PRIDE project
     2. Name: Acquisition of mecA confers resistance to inhibition of Clostridioides difficile sporulation by cephamycins.