Imperial College London

DrGeraldLarrouy-Maumus

Faculty of Natural SciencesDepartment of Life Sciences

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 7463g.larrouy-maumus

 
 
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Location

 

3.42Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Sabnis:2018:10.1101/479618,
author = {Sabnis, A and Klöckner, A and Becce, M and Hagart, KLH and Evans, LE and Furniss, RCD and Mavridou, DAI and Larrouy-Maumus, GJ and Stevens, MM and Edwards, AM},
doi = {10.1101/479618},
publisher = {Cold Spring Harbor Laboratory},
title = {Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane},
url = {http://dx.doi.org/10.1101/479618},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - UNPB
AB - <jats:title>Summary</jats:title><jats:p>Colistin is an antibiotic of last resort for infections caused by drug-resistant Gram-negative pathogens such as <jats:italic>Pseudomonas aeruginosa</jats:italic> and <jats:italic>Escherichia coli</jats:italic>. For this reason, high rates of treatment failure and increasing resistance to this antibiotic are very concerning and attempts to resolve these issues are hampered by a poor understanding of colistin’s mode of action. Whilst it is well established that colistin binds to lipopolysaccharide in the bacterial outer membrane, it was unclear how this led to bacterial killing. Here, we show that colistin also targets lipopolysaccharide in the cytoplasmic membrane and that this interaction is essential for cytoplasmic membrane permeabilisation, cell lysis and the bactericidal activity of the antibiotic. We also found that MCR-1-mediated colistin resistance confers protection against the antibiotic via the presence of modified lipopolysaccharide within the cytoplasmic membrane, rather than the outer membrane. These findings reveal key details about the mechanism by which colistin kills bacteria, providing the foundations for the development of new approaches to enhance therapeutic outcomes.</jats:p>
AU - Sabnis,A
AU - Klöckner,A
AU - Becce,M
AU - Hagart,KLH
AU - Evans,LE
AU - Furniss,RCD
AU - Mavridou,DAI
AU - Larrouy-Maumus,GJ
AU - Stevens,MM
AU - Edwards,AM
DO - 10.1101/479618
PB - Cold Spring Harbor Laboratory
PY - 2018///
TI - Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane
UR - http://dx.doi.org/10.1101/479618
ER -