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Production and characterization of stable amphotericin-resistant amastigotes and promastigotes of Leishmania mexicana

Al-Mohammed, Hamdan I and Chance, Michael L and Bates, Paul A (2005) Production and characterization of stable amphotericin-resistant amastigotes and promastigotes of Leishmania mexicana. Antimicrobial Agents and Chemotherapy, 49 (8). pp. 3274-3280. ISSN 0066-4804

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Abstract

The sensitivities of Leishmania mexicana amastigote and promastigote forms to amphotericin B were investigated in vitro and found to be strongly influenced by the culture media used. When differences in culture media were minimized, there was no significant difference in the 50% inhibitory concentration values between the two life cycle stages. Stable amphotericin B-resistant amastigote and promastigote lines were produced by the application of increasing drug pressure to long-term cultures. Lines capable of growth in concentrations of amphotericin B lethal to normal parasites were produced. Compared to normal parasites, these amphotericin-resistant lines showed marked differences in membrane sterol compositions, with very high levels of 4,14,dimethyl-cholesta-8,24-dienol and other methyl sterols. They also showed a consistent morphological feature, the presence of multilamellar membrane-like material in the flagellar pocket, revealed by transmission electron microscopy. Amphotericin-resistant parasites were capable of infecting BALB/c mice, but the resulting lesion growth was slower than that after infection with normal parasites. However, unlike normal parasites, the amphotericin-resistant parasites were unaffected by experimental chemotherapy with amphotericin B. These results show that amphotericin B resistance could arise as a result of increased clinical use of amphotericin B therapy.

Item Type: Article
Journal or Publication Title: Antimicrobial Agents and Chemotherapy
Subjects: Q Science > QR Microbiology > QR355 Virology
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 56043
Deposited By: ep_importer_pure
Deposited On: 20 Jul 2012 13:33
Refereed?: Yes
Published?: Published
Last Modified: 09 Apr 2014 23:50
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/56043

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