Evidence map›Paper›PMID 42457728›Full record

ArticleNature communications2026

Uncovering an alternate pathway of antibiotic resistance in spore-forming bacteria.

Yogitha N Srikhanta, Clara E Bate, Desirel Ng, Sarah A Revitt-Mills, Georgia-Rose Gilmore, Galain C Williams, Sophie L Day, Stéphane Mesnage, Kamila Kochan, Shailab Shrestha and 16 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Yogitha N Srikhanta *Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.
Clara E Bate *Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0000-0002-4983-8483
Desirel NgInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0009-0008-5455-8081
Sarah A Revitt-MillsInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0000-0001-7215-6459
Georgia-Rose GilmoreInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.
Galain C WilliamsInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0000-0001-9347-7198
Sophie L DayInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.
Stéphane MesnageMolecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, UK.ORCID http://orcid.org/0000-0003-1648-4890
Kamila KochanCentre to Impact AMR, Monash University, Melbourne, VIC, Australia.
Shailab ShresthaDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
Aimee ShenDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9786-5742
Daniel R KnightDepartment of Microbiology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, WA, Australia.ORCID http://orcid.org/0000-0002-9480-4733
Korakrit ImwattanaSchool of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia.
Thomas V RileyDepartment of Microbiology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, WA, Australia.ORCID http://orcid.org/0000-0002-1351-3740
Irene AlevizosInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0009-0008-8299-0584
Kimberley BourkeInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0009-0000-1906-4117
Milena M AwadInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0000-0002-9275-3979
Caroline A EvansSchool of Chemical, Materials and Biological Engineering, University of Sheffield, Sheffield, UK.ORCID http://orcid.org/0000-0003-4356-9216
Ghizal SiddiquiDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0002-3153-3198
Joel R SteeleMonash Proteomics & Metabolomics Platform, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0000-0002-3070-9761
David L SteerMonash Proteomics & Metabolomics Platform, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0000-0001-5656-1569
Joshua P MorrowDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Darren J CreekDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-7497-7082
Chaille WebbInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.
Sheena McGowanInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0000-0001-6863-1106
Dena LyrasInfection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia. Dena.Lyras@monash.edu.ORCID http://orcid.org/0000-0003-2345-9271

Funding

Department of Education and Training | Australian Research Council (ARC) DP190102969Department of Education and Training | Australian Research Council (ARC) FL210100258Department of Health | National Health and Medical Research Council (NHMRC) GNT1138257RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/M012166/1RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) BB/W013800/1RCUK | Medical Research Council (MRC) MR/S009272/1
6 · The paper itself

Abstract

Spore-forming bacteria produce two distinct cell types: vegetative cells and resilient spores. While antibiotic resistance is typically associated with vegetative cells, spores play a critical role in disseminating resistance genes due to their durability and transmissibility. We previously demonstrated that cephamycin antibiotics target the conserved spore-specific protein SpoVD, significantly reducing spore formation in pathogens including Clostridioides difficile. Here, we show that when C. difficile acquires CdmecA, a homologue of Staphylococcus aureus mecA, one of the most globally burdensome resistance genes, the anti-sporulation effect of cephamycins is bypassed. CdMecA functionally replaces CdSpoVD, restoring sporulation and producing phenotypically distinct spores. We further show that mecA is prevalent across C. difficile strains and other pathogenic, gut, and environmental spore-formers. Since SpoVD is conserved, MecA may broadly co-opt sporulation; we confirm this in Clostridium perfringens. This work reveals an unusual resistance mechanism with unexpected physiological consequences, reshaping our understanding of antibiotic resistance within the context of sporulation and microbial adaptation.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsClostridioides difficileDrug Resistance, BacterialSpores, BacterialClostridium perfringensGene Expression Regulation, BacterialPenicillin-Binding ProteinsStaphylococcus aureusAnti-Bacterial AgentsBacterial ProteinsmecA protein, Staphylococcus aureusPenicillin-Binding Proteins

Identifiers

PMID42457728
PMCPMC13490422

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.