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@unpublished{Humphrey:2021:10.1101/2021.07.21.453182,
author = {Humphrey, M and Larrouy-Maumus, GJ and Furniss, RCD and Mavridou, DAI and Sabnis, A and Edwards, AM},
doi = {10.1101/2021.07.21.453182},
title = {Colistin resistance in <i>Escherichia coli</i> confers protection of the cytoplasmic but not outer membrane from the polymyxin antibiotic},
url = {http://dx.doi.org/10.1101/2021.07.21.453182},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:p>Colistin is a polymyxin antibiotic of last resort for the treatment of infections caused by multi-drug resistant Gram-negative bacteria. By targeting lipopolysaccharide (LPS), the antibiotic disrupts both the outer and cytoplasmic membranes, leading to lysis and bacterial death. Colistin resistance in <jats:italic>Escherichia coli</jats:italic> occurs via mutations in the chromosome or the acquisition of mobilised colistin resistance (<jats:italic>mcr</jats:italic>) genes. Both these colistin resistance mechanisms result in chemical modifications to the LPS, with positively charged moieties added at the cytoplasmic membrane before the LPS is transported to the outer membrane. We have previously shown that MCR-1-mediated LPS modification protects the cytoplasmic but not the outer membrane from damage caused by colistin, enabling bacterial survival. However, it remains unclear whether this observation extends to colistin resistance conferred by other <jats:italic>mcr</jats:italic> genes, or resistance due to chromosomal mutations. Using a panel of clinical <jats:italic>E. coli</jats:italic> that had acquired <jats:italic>mcr</jats:italic> -1, -1.5, -2, -3, -3.2 or -5, or had acquired polymyxin resistance independently of <jats:italic>mcr</jats:italic> genes, we found that almost all isolates were susceptible to colistin-mediated permeabilisation of the outer, but not cytoplasmic, membrane. Furthermore, we showed that permeabilisation of the outer membrane of colistin resistant isolates by the polymyxin is in turn sufficient to sensitise bacteria to the antibiotic rifampicin, which normally cannot cross the LPS monolayer. These findings demonstrate that colistin resistance in <jats:italic>E. coli</jats:italic> is typically due to protection of the cytoplasmic but not outer membrane from colistin-mediated damage, regardless of th
AU  - Humphrey,M
AU  - Larrouy-Maumus,GJ
AU  - Furniss,RCD
AU  - Mavridou,DAI
AU  - Sabnis,A
AU  - Edwards,AM
DO  - 10.1101/2021.07.21.453182
PY  - 2021///
TI  - Colistin resistance in <i>Escherichia coli</i> confers protection of the cytoplasmic but not outer membrane from the polymyxin antibiotic
UR  - http://dx.doi.org/10.1101/2021.07.21.453182
ER  -
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