Production and characterization of stable amphotericin-resistant amastigotes and promastigotes of Leishmania mexicana.
Antimicrob Agents Chemother
; 49(8): 3274-80, 2005 Aug.
Article
en En
| MEDLINE
| ID: mdl-16048936
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leishmania mexicana
/
Resistencia a Medicamentos
/
Anfotericina B
/
Antiprotozoarios
Límite:
Animals
País/Región como asunto:
Mexico
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2005
Tipo del documento:
Article
País de afiliación:
Reino Unido