Journal article
Enhanced resistance of metal sequestering agents by reconfiguration of the Staphylococcus aureus cell wall
NPJ ANTIMICROBIALS AND RESISTANCE, Vol.3(1), 61
07/03/2025
DOI: 10.1038/s44259-025-00131-1
PMCID: PMC12229560
PMID: 40610653
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.
Details
- Title: Subtitle
- Enhanced resistance of metal sequestering agents by reconfiguration of the Staphylococcus aureus cell wall
- Creators
- Joy R Paterson - Durham UniversityJoshua M Wadsworth - Durham UniversityRebecca J Lee - Durham UniversityPing Hu - Procter & GambleJacob Biboy - Newcastle UniversityDaniela Vollmer - Newcastle UniversityWaldemar Vollmer - Newcastle UniversityJon Marles-Wright - Newcastle UniversityJana N Radin - University of IowaThomas E Kehl-Fie - University of IowaMary T Moran - Procter & Gamble Technical Centres, Reading, Berkshire, UKGary J Sharples - Durham University
- Resource Type
- Journal article
- Publication Details
- NPJ ANTIMICROBIALS AND RESISTANCE, Vol.3(1), 61
- DOI
- 10.1038/s44259-025-00131-1
- PMID
- 40610653
- PMCID
- PMC12229560
- NLM abbreviation
- NPJ Antimicrob Resist
- ISSN
- 2731-8745
- eISSN
- 2731-8745
- Publisher
- SPRINGERNATURE
- Grant note
- BB/T008695/1 / Biotechnology and Biological Sciences Research Council Alert'17; BB/R013942/1 / Biotechnology and Biological Sciences Research Council BB/W013630/1 / Biotechnology and Biological Sciences Research Council 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" / University of Iowa Research Grant / Procter and Gamble Fund N/A / Procter and Gamble R01AI179695 / NIH HHS
- Language
- English
- Date published
- 07/03/2025
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984843603902771
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