Imperial College London
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DrDespoinaMavridou

Faculty of Natural Sciences, Department of Life Sciences

Visiting Researcher
 
 
 
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Contact

 

d.mavridou

 
 
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Location

 

1.45Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gadar:2023:10.1038/s42003-023-05302-2,
author = {Gadar, K and de, Dios R and Kadeábková, N and Prescott, TAK and Mavridou, DAI and McCarthy, RR},
doi = {10.1038/s42003-023-05302-2},
journal = {Commun Biol},
title = {Disrupting iron homeostasis can potentiate colistin activity and overcome colistin resistance mechanisms in Gram-Negative Bacteria.},
url = {http://dx.doi.org/10.1038/s42003-023-05302-2},
volume = {6},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Gadar,K
AU  - de,Dios R
AU  - Kadeábková,N
AU  - Prescott,TAK
AU  - Mavridou,DAI
AU  - McCarthy,RR
DO  - 10.1038/s42003-023-05302-2
PY  - 2023///
TI  - Disrupting iron homeostasis can potentiate colistin activity and overcome colistin resistance mechanisms in Gram-Negative Bacteria.
T2  - Commun Biol
UR  - http://dx.doi.org/10.1038/s42003-023-05302-2
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37704838
VL  - 6
ER  -
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