Imperial College London
Alternate

ProfessorHuwWilliams

Faculty of Natural Sciences, Department of Life Sciences

Professor of Microbiology
 
 
 
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Contact

 

+44 (0)20 7594 5383h.d.williams

 
 
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Location

 

507Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bradley:2024:10.1128/msystems.01165-23,
author = {Bradley, R and Simon, D and Spiga, L and Xiang, Y and Takats, Z and Williams, H},
doi = {10.1128/msystems.01165-23},
journal = {mSystems},
title = {Laser desorption rapid evaporative ionization mass spectrometry (LD-REIMS) demonstrates a direct impact of hypochlorous acid stress on PQS-mediated quorum sensing in Pseudomonas aeruginosa.},
url = {http://dx.doi.org/10.1128/msystems.01165-23},
volume = {9},
year = {2024}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - UNLABELLED: To establish infections in human hosts, Pseudomonas aeruginosa must overcome innate immune-generated oxidative stress, such as the hypochlorous acid (HOCl) produced by neutrophils. We set out to find specific biomarkers of oxidative stress through the development of a protocol for the metabolic profiling of P. aeruginosa cultures grown in the presence of different oxidants using a novel ionization technique for mass spectrometry, laser desorption rapid evaporative ionization mass spectrometry (LD-REIMS). We demonstrated the ability of LD-REIMS to classify samples as untreated or treated with a specific oxidant with 100% accuracy and identified a panel of 54 metabolites with significantly altered concentrations after exposure to one or more of the oxidants. Key metabolic changes were conserved in P. aeruginosa clinical strains isolated from patients with cystic fibrosis lung infections. These data demonstrated that HOCl stress impacted the Pseudomonas quinolone signal (PQS) quorum sensing system. Ten 2-alkyl-4-quinolones (AHQs) associated with the PQS system were significantly lower in concentration in HOCl-stressed P. aeruginosa cultures, including 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), the most active signal molecule of the PQS system. The PQS system regulates the production of virulence factors, including pyocyanin and elastase, and their levels were markedly affected by HOCl stress. No pyocyanin was detectable and elastase concentrations were reduced by more than 75% in cultures grown with sub-lethal concentrations of HOCl, suggesting that this neutrophil-derived oxidant may disrupt the ability of P. aeruginosa to establish infections through interference with production of PQS-associated virulence factors. IMPORTANCE: This work demonstrates that a high-throughput ambient ionization mass spectrometry method can be used successfully to study a bacterial stress response. Its application to the opportunistic pathogen Pseudomonas aeruginosa led to the
AU  - Bradley,R
AU  - Simon,D
AU  - Spiga,L
AU  - Xiang,Y
AU  - Takats,Z
AU  - Williams,H
DO  - 10.1128/msystems.01165-23
PY  - 2024///
TI  - Laser desorption rapid evaporative ionization mass spectrometry (LD-REIMS) demonstrates a direct impact of hypochlorous acid stress on PQS-mediated quorum sensing in Pseudomonas aeruginosa.
T2  - mSystems
UR  - http://dx.doi.org/10.1128/msystems.01165-23
UR  - https://www.ncbi.nlm.nih.gov/pubmed/38530056
VL  - 9
ER  -
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