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Cited by 389

The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.

Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane

Open access
Sabnis, Akshay, Hagart, Katheryn LH, Klöckner, Anna, Becce, Michele, Evans, Lindsay E, Furniss, R Christopher D, Mavridou, Despoina AI, Murphy, Ronan, Stevens, Molly M, Davies, Jane C, Larrouy-Maumus, Gérald J, Clarke, Thomas B, Edwards, Andrew M·2021·eLife

Abstract

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.

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Metadata

Authors
Sabnis, A., Hagart, K. L., Klöckner, A., Becce, M., Evans, L. E., Furniss, R. C. D., Mavridou, D. A., Murphy, R., Stevens, M. M., Davies, J. C., Larrouy-Maumus, G. J., Clarke, T. B., & Edwards, A. M.
Venue
eLife
Published
2021-04-06
Volume
10
ISSN
2050-084X (ISSN-L)
OpenAlex
W3140198700
Cited by
389
References
68
FWCI
15.21
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane. https://app.cochat.ai/papers/10.7554/elife.65836
The paper
Sabnis, A., Hagart, K. L., Klöckner, A., Becce, M., Evans, L. E., Furniss, R. C. D., Mavridou, D. A., Murphy, R., Stevens, M. M., Davies, J. C., Larrouy-Maumus, G. J., Clarke, T. B., & Edwards, A. M. (2021). Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane. eLife. https://doi.org/10.7554/elife.65836

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