Evidence map›Paper›PMID 42298145›Full record

Articlenpj antimicrobials and resistance2026

Overcoming methicillin resistance in Staphylococcus aureus via metal ion disruption of bacterial metabolism.

Ella K Macbeth, Francesca Todd Rose, Chen-Yi Cheung, Nichaela Harbison-Price, David M P De Oliveira, Hayden G Whyte, Mark J Walker, Maytham Hussein, Tony Velkov, Stephanie L Neville and 4 more

Abstract read
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In one paragraph

Article in npj antimicrobials and resistance, 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

14 authors.

Ella K MacbethDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Francesca Todd RoseDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Chen-Yi CheungDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Nichaela Harbison-PriceThe Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
David M P De OliveiraThe Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Hayden G WhyteThe Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Mark J WalkerThe Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Maytham HusseinMonash Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Melbourne, VIC, Australia.
Tony VelkovMonash Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Melbourne, VIC, Australia.
Stephanie L NevilleDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, VIC, Australia.
Christopher A McDevittDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, VIC, Australia.
Ian R MonkDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, VIC, Australia.
Scott A FergusonDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Gregory M CookDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand. greg.cook@otago.ac.nz.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant public health threat due to both extensive antimicrobial resistance and immune evasion capabilities, necessitating alternative therapeutic strategies. Disruption of bacterial metal ion homeostasis, a process already leveraged by host nutritional immunity, represents a promising therapeutic approach. The synthetic ionophore PBT2 delivers zinc (Zn) directly into the bacterial cytosol, where it can dysregulate cellular processes and restore the efficacy of conventional antibiotics. Here, we use PBT2 and Zn (PZ) to study the cellular response to metal dysbiosis in MRSA, identifying new metal-dependent molecular vulnerabilities. Integrated transcriptomics, metabolomics and molecular analyses revealed that the antibacterial and oxacillin-resensitisation action of PZ is driven by dual metal stress: intracellular Zn accumulation and manganese (Mn) depletion. PZ disrupted central carbon metabolism at multiple key nodes, impairing glycolysis, the TCA cycle and respiration, leading to NADH and ATP depletion and compromised peptidoglycan biosynthesis. PZ also altered the metal-dependent oxidative stress response, resulting in superoxide accumulation. Collectively, this work presents the dynamic interplay between bacterial metal ion homeostasis, central metabolism, and β-lactam resistance. Uncovering how PBT2 subverts the adaptive responses of MRSA to host-imposed stresses contributes to our understanding of host-pathogen interactions and offers a foundation for developing novel antimicrobials based on metal homeostasis disruption.

Identifiers

PMID42298145
PMCPMC13646252

What OpenQuestion holds

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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.