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

Al-Mohammed, H. I., Chance, Michael and Bates, Paul (2005) 'Production and characterization of stable amphotericin-resistant amastigotes and promastigotes of Leishmania mexicana'. Antimicrobial Agents and Chemotherapy, Vol 49, Issue 8, pp. 3274-3280.

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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 ampbotericin B. These results show that amphotericin B resistance could arise as a result of increased clinical use of amphotericin B therapy.

Item Type: Article
Subjects: QX Parasitology > QX 4 General works
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 715 Visceral leishmaniasis
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1128/AAC.49.8.3274-3280.2005
Depositing User: Ms Julia Martin
Date Deposited: 23 Sep 2011 15:45
Last Modified: 06 Feb 2018 13:02
URI: http://archive.lstmed.ac.uk/id/eprint/1853

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