ArticleCommunications biology2023
Disrupting iron homeostasis can potentiate colistin activity and overcome colistin resistance mechanisms in Gram-Negative Bacteria.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Disruption ofVirulence · 2026Article
- Kaempferol: advances in biosynthesis, molecular mechanisms, and therapeutic applications.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Antibacterial and anti-biofilm mechanisms of 1,8-cineole against colistin-resistant Acinetobacter baumannii: an integrated in vitro, gene expression, and in silico study.Scientific reports · 2026Article
- Single-bacterial cell insights into mechanisms of ceftriaxone resistance in Neisseria subflava.Nature communications · 2026Article
- Bogland plant Tormentil inhibits multidrug-resistant pathogen growth and potentiates antibiotics by disrupting iron homeostasis.Microbiology (Reading, England) · 2026Article
- Bacterial cell envelope-targeting antibiotics.Nature reviews. Microbiology · 2026Review
- Natural compounds: a promising therapeutic option for managing colistin-resistant bacteria and improving colistin activity.Molecular biology reports · 2026Review
- Colistin Resistance in Bacteria: Current Updates on Mechanism of Action and Combating Strategies.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026Review
- Current progress in antibacterial agents for carbapenem-resistant enterobacterales.Frontiers in pharmacology · 2026Review
- Advances in Kaempferol: Extraction, Biosynthesis, and Application with Antibacterial Agents.Antibiotics (Basel, Switzerland) · 2025Review
- Polymyxin B lethality requires energy-dependent outer membrane disruption.Nature microbiology · 2025Article
- Bakuchiol, a Natural Antioxidant, Synergizes with Colistin Against Multidrug-Resistant Gram-Negative Bacteria by Disrupting Iron Homeostasis and Membrane Integrity.Antioxidants (Basel, Switzerland) · 2025Article
- Host niche-specific challenges hindering the treatment of polymicrobial infections.Journal of bacteriology · 2025Review
- A strategic approach to regulating new antimicrobials.Journal of global health · 2025Article
- Matrine Restores Colistin Efficacy AgainstMolecules (Basel, Switzerland) · 2025Article
- Harnessing the effect of iron deprivation to attenuate the growth of opportunistic pathogenAntimicrobial agents and chemotherapy · 2025Article
- The diversity and applications of microbial iron metabolism and iron-containing proteins.Communications biology · 2025Article
- Colistin Resistance Mechanism and Management Strategies of Colistin-ResistantPathogens (Basel, Switzerland) · 2024Review
- Valnemulin restores colistin sensitivity against multidrug-resistant gram-negative pathogens.Communications biology · 2024Article
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Acinetobacter baumannii is a Gram-negative priority pathogen that can readily overcome antibiotic treatment through a range of intrinsic and acquired resistance mechanisms. Treatment of carbapenem-resistant A. baumannii largely relies on the use of colistin in cases where other treatment options have been exhausted. However, the emergence of resistance against this last-line drug has significantly increased amongst clinical strains. In this study, we identify the phytochemical kaempferol as a potentiator of colistin activity. When administered singularly, kaempferol has no effect on growth but does impact biofilm formation. Nonetheless, co-administration of kaempferol with sub-inhibitory concentrations of colistin exposes bacteria to a metabolic Achilles heel, whereby kaempferol-induced dysregulation of iron homeostasis leads to bacterial killing. We demonstrate that this effect is due to the disruption of Fenton's reaction, and therefore to a lethal build-up of toxic reactive oxygen species in the cell. Furthermore, we show that this vulnerability can be exploited to overcome both intrinsic and acquired colistin resistance in clinical strains of A. baumannii and E. coli in vitro and in the Galleria mellonella model of infection. Overall, our findings provide a proof-of-principle demonstration that targeting iron homeostasis is a promising strategy for enhancing the efficacy of colistin and overcoming colistin-resistant infections.
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Registered trials
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.