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Colistin causes profound morphological alteration but minimal cytoplasmic membrane perforation in populations of escherichia coli and pseudomonas aeruginosa.

O'Driscoll, Noëlle H.; Cushnie, T.P. Tim; Matthews, Kerr H.; Lamb, Andrew J.

Authors

Noëlle H. O'Driscoll

T.P. Tim Cushnie

Kerr H. Matthews

Andrew J. Lamb

Abstract

Whilst colistin (polymyxin E) represents the last mainstream treatment option for multi-drug resistant Gram-negative pathogens, details of its mechanism of action remain to be fully resolved. In this study, the effects of sub-inhibitory, inhibitory-bactericidal, and supra-bactericidal levels of colistin on the membrane integrity and morphology of Escherichia coli and Pseudomonas aeruginosa were investigated using potassium loss, flow cytometry, and scanning electron microscopy (SEM). Supra-bactericidal colistin concentrations induced just 4-12% intracellular potassium loss from bacteria after 24 h. Flow cytometry data suggested colistin might alter cell arrangement, and SEM confirmed the antibiotic causes bacterial aggregation. Filamentation was not detected in either species at any concentration or time-point up to 24 h. These results argue against the hypotheses that colistin kills bacteria by puncturing the cytoplasmic membrane or disrupting DNA synthesis. The colistin-induced bacterial aggregation detected has implications for the interpretation of MBC, time-kill, and other test results obtained with this antibiotic.

Journal Article Type Article
Publication Date Jul 31, 2018
Journal Archives of microbiology
Print ISSN 0302-8933
Electronic ISSN 1432-072X
Publisher Springer (part of Springer Nature)
Peer Reviewed Peer Reviewed
Volume 200
Issue 5
Pages 793-802
Institution Citation O'DRISCOLL, N.H., CUSHNIE, T.P.T., MATTHEWS, K.H. and LAMB, A.J. 2018. Colistin causes profound morphological alteration but minimal cytoplasmic membrane perforation in populations of escherichia coli and pseudomonas aeruginosa. Archives of microbiology [online], 200(5), pages 793-802. Available from: https://doi.org/10.1007/s00203-018-1485-3
DOI https://doi.org/10.1007/s00203-018-1485-3
Keywords Colistin; Polymyxin E; Mechanism of action; Mode of action; Flow cytometry; SEM

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