Colistin causes profound morphological alteration but minimal cytoplasmic membrane perforation in populations of Escheri
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ORIGINAL PAPER
Colistin causes profound morphological alteration but minimal cytoplasmic membrane perforation in populations of Escherichia coli and Pseudomonas aeruginosa Noëlle H. O’Driscoll1 · T. P. Tim Cushnie2 · Kerr H. Matthews1 · Andrew J. Lamb1,3 Received: 20 October 2017 / Revised: 19 January 2018 / Accepted: 24 January 2018 © The Author(s) 2018. This article is an open access publication
Abstract Whilst colistin (polymyxin E) represents the last mainstream treatment option for multidrug-resistant Gram-negative pathogens, details of its mechanism of action remain to be fully resolved. In this study, the effects of sub-inhibitory, inhibitorybactericidal, 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. Keywords Colistin · Polymyxin E · Mechanism of action · Mode of action · Flow cytometry · SEM
Introduction Colistin (polymyxin E) is an antibiotic with a spectrum of activity that includes problematic carbapenem-resistant and extensively drug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli. Systemic use of colistin largely ceased in the 1970s due to concerns Communicated by Erko Stackebrandt. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00203-018-1485-3) contains supplementary material, which is available to authorized users. * Andrew J. Lamb [email protected] 1
School of Pharmacy and Life Sciences, Robert Gordon University, Sir Ian Wood Building, Garthdee Road, Aberdeen AB10 7GJ, UK
2
Faculty of Medicine, Mahasarakham University, Khamriang, Kantarawichai, Maha Sarakham 44150, Thailand
3
Graduate School, Robert Gordon University, Health and Social Care Building, Garthdee Road, Aberdeen AB10 7QG, UK
about nephrotoxicity and neurotoxicity, but growing resistance to other antibiotic classes prompted a reassessment of its safety at the turn of the century (Tängdén and Giske 2015; Tran et al. 2016). Under suitable dosage regimens and with careful monitoring, it is now accepted that the risk of colistin-induced kidney or nerve damage can be minimized (Kelesidis and Falagas 2015; Shields et al. 2017), and the antibiotic has been returned to use as a last option or salvage therapy (Poirel et a
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