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

O'Driscoll, No�lle H.; Cushnie, T.P. Tim; Matthews, Kerr H.; Lamb, Andrew J.

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.

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

• Journal Article Type: Article
• Acceptance Date: Jan 24, 2018
• Online Publication Date: Feb 8, 2018
• Publication Date: Jul 31, 2018
• Deposit Date: Jan 25, 2018
• Publicly Available Date: Jan 25, 2018
• Journal: Archives of microbiology
• Print ISSN: 0302-8933
• Electronic ISSN: 1432-072X
• Publisher: Springer
• Peer Reviewed: Peer Reviewed
• Volume: 200
• Issue: 5
• Pages: 793-802
• DOI: https://doi.org/10.1007/s00203-018-1485-3
• Keywords: Colistin; Polymyxin E; Mechanism of action; Mode of action; Flow cytometry; SEM
• Public URL: http://hdl.handle.net/10059/2690
• Contract Date: Jan 25, 2018