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:
Journal Article
Journal or Publication Title:
Antimicrobial Agents and Chemotherapy
Uncontrolled Keywords:
/dk/atira/pure/researchoutput/libraryofcongress/qr355
Subjects:
ID Code:
56043
Deposited By:
Deposited On:
20 Jul 2012 12:33
Refereed?:
Yes
Published?:
Published
Last Modified:
06 May 2020 02:25