Treatment of murine cryptococcosis with minocycline and amphotericin B

Graybill, John R.; Mitchell, Linda

doi:10.1080/00362178085380221

Cited by 9 publications

(6 citation statements)

References 8 publications

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“…With the increased use of TET in inducible promoter systems, and with the previously reported altered susceptibility to AMB (Graybill & Mitchell, 1980;Raab & Hogl, 1980;Siau & Kerridge, 1998), it is important to understand the effects of TET on a cell, and to distinguish TET-related effects from gene expression phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…In the 1970s and 1980s, synergy between TET and AMB was observed clinically and in animal models with wildtype strains of C. albicans, Aspergillus species and Cryptococcus species (Graybill & Mitchell, 1980;Kwan et al, 1972;Odds et al, 1986;Raab & Hogl, 1980;Rubin et al, 1983). However, no molecular mechanism was elucidated at the time for any of these species and it is important to revisit this phenomenon as the use of TETregulatable promoters in these species has become increasingly common and as standardized methods of determining MIC have been defined.…”

Section: Introductionmentioning

confidence: 99%

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Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi

et al. 2008

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The tetracycline (TET) promoter has been used in several systems as an inducible regulator of gene expression. In control analyses, the standard Candida albicans laboratory strain SC5314 was found to have altered susceptibility to a variety of antifungal drugs in the presence of relatively high concentrations (50-200 mg ml "1 ) of TET. Altered susceptibility was most notable with exposure to amphotericin B (AMB), with a 32-fold increase in susceptibility, and terbinafine (TRB), with a 32-fold decrease in susceptibility. The TET/AMB synergy was observed in several clinical isolates of C. albicans and in the distantly related species Aspergillus fumigatus and Cryptococcus neoformans. The TET/AMB synergy is not related to efflux pump activity, as determined by FACS analyses and by analysis of a strain containing efflux pump deletions. Gene expression analyses by luciferase and by quantitative real-time reverse transcriptase PCR failed to identify significant alterations in expression of any genes associated with resistance. C. albicans grown with TET for 48 h does show a reduction in total cellular ergosterol. Analysis of growth curves suggests that the TET effect is associated with lack of a diauxic shift, which is related to a loss of mitochondrial function. MitoTracker fluorescent dye was used to demonstrate that TET has a direct effect on mitochondrial function. These results demonstrate the need for careful analysis of TET effects when using a TET-inducible promoter, especially in studies that involve antifungal drugs. This study defines some limits to the use of the TET-inducible promoter, and identifies effects on cells that are the result of TET exposure alone, not the result of expression of a targeted gene.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi

et al. 2008

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“…New et al (16), for example, showed that liposomeincorporated amphotericin B was less toxic and more active against experimental Leishmaniasis than the free drug. A lower toxicity and an equal therapeutic efficacy were observed by Taylor et al (18) against experimental histoplasmosis, by Graybill et al (17) against experimental cryptococcosis, and by LopezBerestein (27) and Lopez-Berestein et al (19,20) against experimental candidiasis.…”

Section: Introductionmentioning

confidence: 76%

“…The ability of intravenously administered amphotericin B to form channels by interaction with cholesterol in mammalian plasma membranes (4), but with a lower affinity than with fungal ergosterol (4,28), could be the basis for its haematopoietic, nephrotic and central nervous system toxicities (9 -11). Since amphotericin B is the drug of choice for most systemic mycoses, arising as complications in patients with haematological malignancies (12,13) and in immunocompromised patients (14,15), attempts have been made to reduce its toxicity and to improve its therapeutic efficacy by incorporating it into liposomes prior to its intravenous injection (16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Alteration of the Permeability of the Human Erythrocyte Membrane to Cations by Liposome-Incorporated Amphotericin B

1992

Clinical Chemistry and Laboratory Medicine

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Summary: Some effects of liposome-incorporated amphotericin B on the permeability of the human erythrocyte membrane to potassium and sodium ions is reported. The influence of cholesterol and amphotericin B in causing a shift towards smaller and larger liposomes, respectively, is also described. Phosphatidylcholine liposomes containing amphotericin B in a molar ratio of 7.4 + 0.1 (mean ± SD) antibiotic to 1000 phospholipid reduced the initial rates of K + and Na + transport across the erythrocyte membrane to 40 + 2.6% and 0%, respectively, of their rates in the presence of comparable concentrations of free amphotericin B. Amphotericin B incorporated into liposomes (8.2 + 0.15 μηιοί antibiotic per 1000 μηιοί total lipid) composed of cholesterol and phosphatidylcholine (in a molar ratio of 3 : 7) reduced the initial rate of K + transport to 19 ± 0.8% of its value measured in the presence of a comparable concentration of free antibiotic. These results suggest that liposomes containing specified amounts of amphotericin B, especially liposomes also containing cholesterol in addition to phosphatidylcholine, could be used as a method of controlling K+ transport across the erythrocyte and possibly other types of cellular membranes, thereby limiting antibiotic toxicity to some mammalian tissues.

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“…The role ofliposome-encapsulated amphotericin Bin human cryptococcosis has not been evaluated, but such therapy is effective in murine cryptococcosis (72). Prophylaxis: Whereas triazole antifungals such as itraconazole and saperconazole may prove to be as effective as fluconazole for secondary prophylaxis of cryptococcosis, is extremely doubtful that they will prove to be more effective.…”

Section: Treatment-unanswered Questionsmentioning

confidence: 99%

Opportunistic Infections in HIV‐Infected Patients

Shafran

1992

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Treatment of murine cryptococcosis with minocycline and amphotericin B

Cited by 9 publications

References 8 publications

Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi

Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi

Alteration of the Permeability of the Human Erythrocyte Membrane to Cations by Liposome-Incorporated Amphotericin B

Opportunistic Infections in HIV‐Infected Patients

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