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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Production and characterization of stable amphotericin-resistant amastigotes and promastigotes of Leishmania mexicana
Antimicrobial Agents and Chemotherapy, Volume 49, No. 8, Year 2005
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Description
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. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Al-Mohammed, Hamdan Ibrahim
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Saudi Arabia, Al-ahsa
King Faisal University
Chance, Michael L.
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Bates, Paul Andrew
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Statistics
Citations: 49
Authors: 3
Affiliations: 2
Identifiers
Doi:
10.1128/AAC.49.8.3274-3280.2005
ISSN:
00664804
Research Areas
Cancer