In this section
@article{Sabnis:2021:10.7554/eLife.65836,
author = {Sabnis, A and Haggard, K and Kloeckner, A and Becce, M and Evans, L and Furniss, R and Mavridou, D and Stevens, M and Murphy, R and Davies, J and Clarke, T and Edwards, A},
doi = {10.7554/eLife.65836},
journal = {eLife},
pages = {1--26},
title = {Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane},
url = {http://dx.doi.org/10.7554/eLife.65836},
volume = {10},
year = {2021}
}
TY - JOUR
AB - 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 (OM) by selectively targeting lipopolysaccharide (LPS), it was unclear how this led to bacterial killing. We discovered that MCR-1 mediated colistin resistance in Escherichia coli is due to modified LPS at the cytoplasmic rather than OM. In doing so, we also demonstrated that colistin exerts bactericidal activity by targeting LPS in the cytoplasmic membrane (CM). 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 CM of Pseudomonas aeruginosa, which resulted in increased susceptibility to colistin in vitro and improved treatment efficacy in vivo. These findings reveal new insight into the mechanism by which colistin kills bacteria, providing the foundations for novel approaches to enhance therapeutic outcomes.
AU - Sabnis,A
AU - Haggard,K
AU - Kloeckner,A
AU - Becce,M
AU - Evans,L
AU - Furniss,R
AU - Mavridou,D
AU - Stevens,M
AU - Murphy,R
AU - Davies,J
AU - Clarke,T
AU - Edwards,A
DO - 10.7554/eLife.65836
EP - 26
PY - 2021///
SN - 2050-084X
SP - 1
TI - Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane
T2 - eLife
UR - http://dx.doi.org/10.7554/eLife.65836
UR - https://elifesciences.org/articles/65836
UR - http://hdl.handle.net/10044/1/89070
VL - 10
ER -
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