Evidence map›Paper›PMID 40610653›Full record

Articlenpj antimicrobials and resistance2025

Enhanced resistance of metal sequestering agents by reconfiguration of the Staphylococcus aureus cell wall.

Joy R Paterson, Joshua M Wadsworth, Rebecca J Lee, Ping Hu, Jacob Biboy, Daniela Vollmer, Waldemar Vollmer, Jon Marles-Wright, Jana N Radin, Thomas E Kehl-Fie and 2 more

Abstract read
In one paragraph

Article in npj antimicrobials and resistance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

12 authors.

Joy R Paterson *Department of Biosciences, Durham University, Durham, UK.
Joshua M Wadsworth *Department of Biosciences, Durham University, Durham, UK.
Rebecca J LeeDepartment of Biosciences, Durham University, Durham, UK.
Ping HuProcter and Gamble, Mason Business Center, Cincinnati, OH, USA.
Jacob BiboyCentre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Daniela VollmerCentre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Waldemar VollmerCentre for Bacterial Cell Biology, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Jon Marles-WrightBiosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Jana N RadinDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Thomas E Kehl-FieDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Mary T MoranProcter & Gamble Technical Centres, Reading, Berkshire, UK.
Gary J SharplesDepartment of Biosciences, Durham University, Durham, UK. gary.sharples@durham.ac.uk.

Funding

Calprotectin and Antibiotic Activities at the Infection InterfaceR01AI179695 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Brian Patrick Conlon, Thomas Everett Kehl-Fie · 2024 to 2026
$2.3M
Biotechnology and Biological Sciences Research Council Alert'17; BB/R013942/1Biotechnology and Biological Sciences Research Council BB/T008695/1Biotechnology and Biological Sciences Research Council BB/W013630/1NIAID NIH HHS R01 AI179695NIH HHS R01AI179695Procter and Gamble N/AProcter and Gamble Fund Research GrantUniversity of Iowa P3 Strategic Initiatives Program through funding received for the project entitled "High Impact Hiring Initiative (HIHI): A Program to Strategically Recruit and Retain Talented Faculty"
6 · The paper itself

Abstract

Chelators possess antibacterial properties linked to metal sequestration, simulating the action of nutritional immunity in preventing infection. To gain further insight into bacterial adaptation to metal restriction, we isolated mutants of Staphylococcus aureus with enhanced resistance to two synthetic chelators with therapeutic potential. Mutations were identified that altered peptidoglycan metabolism and teichoic acid modification, crucially affecting PBP2 and eliminating FmtA or VraF functionality. The resulting strains showed increased cell wall thickness, modified cell surface charge and varied in susceptibility to cell wall-targeting agents. In those mutants lacking either FmtA or VraF, the modifications substantially increased cell surface-associated calcium, offering protection against loss of manganese that was preferentially targeted by both chelators. Our phenotypic and cellular metal analyses identify the cell envelope of S. aureus as a key target for metal sequestering molecules. Peptidoglycan and teichoic acids, in particular, serve as key repositories for a subset of metal ions that safeguard against deprivation and can be altered to augment resistance to antibacterial chelators.

Identifiers

PMID40610653
PMCPMC12229560

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.