Imperial College London
Alternate

DrGeraldLarrouy-Maumus

Faculty of Natural Sciences, Department of Life Sciences

Reader in Molecular Microbiology
 
 
 
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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@unpublished{Sabnis:2018:10.1101/479618,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 Hagart, KLH and Klöckner, A and Becce, M and Evans, LE and Furniss, RCD and Mavridou, DAI and Murphy, R and Stevens, MM and Davies, JC and Larrouy-Maumus, GJ and Clarke, TB and Edwards, AM},
doi = {10.1101/479618},
title = {Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane},
url = {http://dx.doi.org/10.1101/479618},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Summary</jats:title><jats:p>Colistin is an antibiotic of last resort, but has poor efficacy and resistance is a growing problem. Whilst it is well established that colistin disrupts the bacterial outer membrane by selectively targeting lipopolysaccharide (LPS), it was unclear how this led to bacterial killing. We discovered that MCR-1 mediated colistin resistance is due to modified LPS at the cytoplasmic rather than outer membrane. In doing so, we also demonstrated that colistin exerts bactericidal activity by targeting LPS in the cytoplasmic membrane. We then exploited this information to devise a new therapeutic approach. Using the LPS transport inhibitor murepavadin, we were able to cause LPS accumulation in the cytoplasmic membrane, which resulted in increased susceptibility to colistin <jats:italic>in vitro</jats:italic> and improved treatment efficacy <jats:italic>in vivo</jats:italic>. These findings reveal new insight into the mechanism by which colistin kills bacteria, providing the foundations for novel approaches to enhance therapeutic outcomes.</jats:p>
AU  - Sabnis,A
AU  - Hagart,KLH
AU  - Klöckner,A
AU  - Becce,M
AU  - Evans,LE
AU  - Furniss,RCD
AU  - Mavridou,DAI
AU  - Murphy,R
AU  - Stevens,MM
AU  - Davies,JC
AU  - Larrouy-Maumus,GJ
AU  - Clarke,TB
AU  - Edwards,AM
DO  - 10.1101/479618
PY  - 2018///
TI  - Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane
UR  - http://dx.doi.org/10.1101/479618
ER  -
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