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AAC Accepts, published online ahead of print on 10 December 2007
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Antimicrob. Agents Chemother. doi:10.1128/AAC.00355-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A molecular basis for the resistance of Acanthamoeba tubulins to all major classes of anti-tubulin compounds

Fiona L. Henriquez*, Paul R. Ingram, Stephen P. Muench, David W. Rice, and Craig W. Roberts

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, Scotland, UK, G4 0NR; Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK, S10 2TN

* To whom correspondence should be addressed. Email: fiona.henriquez{at}paisley.ac.uk.


   Abstract

Tubulin is essential to eukaryotic cells and is targeted by several anti-neoplastics, herbicides and antimicrobials. We demonstrate that Acanthamoeba are resistant to five anti-microtubule compounds, unlike any other eukaryote studied so far. Resistance correlates with critical amino acid differences within the inhibitor binding sites of the tubulin heterodimers.







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