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PubMed2002

Testing conditions for determination of minimum fungicidal concentrations of new and established antifungal agents for Aspergillus spp.: NCCLS collaborative study.

Standard conditions are not available for evaluating the minimum fungicidal concentrations (MFCs) of antifungal agents. This multicenter collaborative study investigated the reproducibility in three laboratories of itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B MFCs for 15 selected isolates of Aspergillus spp. After MIC determinations for the 15 isolates in each center by the NCCLS M38-A broth microdilution method with four media, standard RPMI 1640 (RPMI), RPMI with 2% dextrose, antibiotic medium 3 (M3), and M3 with 2% dextrose, MFCs were determined for each isolate-medium-drug combination. MFCs were defined as the lowest drug dilutions that yielded <3 colonies (approximately 99 to 99.5% killing activity). The highest reproducibility (96 to 100%) was for amphotericin B MFCs with the four media. Although reproducibility was more variable and medium dependent for the azoles (91 to 98%), agreement was good to excellent for itraconazole, ravuconazole, and voriconazole MFCs with RPMI and M3 (93 to 98%). For posaconazole, the agreement was higher with M3 media (91 to 96%) than with RPMI media (91%). These data extend the refinement of testing guidelines for susceptibility testing of Aspergillus spp. and warrant consideration for introduction into future versions of the M38 document. The role of the MFC under these standardized testing conditions as a predictor of clinical outcome needs to be established in clinical trials.

Antifungal Agents↗
PubMed2006

Histatin 5-derived peptide with improved fungicidal properties enhances human immunodeficiency virus type 1 replication by promoting viral entry.

Antimicrobial peptides are found in a number of body compartments and are secreted at mucosal surfaces, where they form part of the innate immune system. Many of these small peptides have a broad spectrum of inhibitory activity against bacteria, fungi, parasites, and viruses. Generally, the peptide's mode of action is binding and disruption of membranes due to its amphipathic properties. Histatin 5 is a salivary peptide that inhibits Candida albicans, an opportunistic fungus that causes oropharyngeal candidiasis in a majority of human immunodeficiency virus type 1 (HIV-1)-infected patients progressing towards AIDS. Previously, we increased the fungicidal properties of histatin 5 by replacing amino acids in the active domain of histatin 5 (Dh-5) (A. L. Ruissen, J. Groenink, E. J. Helmerhorst, E. Walgreen-Weterings, W. van't Hof, E. C. Veerman, and A. V. Nieuw Amerongen, Biochem. J. 356:361-368, 2001). In the current study, we tested the anti-HIV-1 activity of Dh-5 and its derivatives. Although Dh-5 inhibited HIV-1 replication, none of the peptide variants were more effective in this respect. In contrast, one of the derivatives, Dhvar2, significantly increased HIV-1 replication by promoting the envelope-mediated cell entry process. Most likely, Dhvar2 affects membranes, thereby facilitating fusion of viral and cellular membranes. This study shows that modification of antimicrobial peptides in order to improve their activity against a pathogen may have unpredictable and unwanted side effects on other pathogens.

Amino Acid Sequence↗
PubMed1998

Fungicidal properties, sterol binding, and proteolytic resistance of the synthetic peptide D4E1.

The fungicidal properties of the synthetic peptide D4E1 were studied with nongerminated and germinating conidia of Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Fusarium moniliforme, and Fusarium oxysporum. The minimal lethal concentrations (MLC) needed to kill 100% of germinating conidia of A. fumigatus, A. flavus, and A. niger were 12.5, 12.5, and 25 microM, respectively. The MLC value for nongerminated and germinating conidia of both Fusarium spp. was 3.0 microM. Except for A. fumigatus, D4E1 was inactive against the nongerminated conidia of the Aspergillus spp. Physicochemical studies showed D4E1 complexed with ergosterol, a sterol present in conidial walls. Cholesterol, present in nongerminated conidia of F. moniliforme, had a greater affinity for D4E1 than did ergosterol. D4E1 was more resistant to fungal and plant protease degradation than the natural peptide, cecropin A. These in vitro results suggest D4E1 is a candidate for transgenic expression in plants to enhance host resistance to fungal infection.

Antifungal Agents↗
PubMed1996

RESISTANCE TO PHENYLAMIDE FUNGICIDES: a case study with phytophthora infestans involving mating type and race structure.

Phenylamide-resistant isolates of Phytophthora infestans have gradually become an important part of populations in many countries. However, fungicide mixtures containing a phenylamide component are still an effective strategy for the control of late blight in potato and tomato. The proportion of phenylamide-resistant isolates fluctuates from year to year and within the season. Almost concurrent with the appearance of resistant isolates was the discovery of the A2 mating type of P. infestans in many European countries and in other parts of the world. However, no genetic correlation exists between resistance and mating type, and the proportion of A2 isolates in European populations remains small. Resistance to phenylamides became established in A1 populations before the appearance of A2 type. Resistant isolates express equal or greater fitness than sensitive isolates, but no correlation was detected between resistance and race structure. The continuous changes in P. infestans populations require careful adaptation of successful disease control programs.

Journal Article↗
PubMedDate not supplied

Clinical impact of the fungicidal activity of caspofungin administered alone or in combination in critically ill patients with severe abdominal candidiasis refractory to conventional antifungal drugs: case studies and critical review of the problem.

We discuss two cases of abdominal candidiasis in critically ill patients with multiple organ failure and sepsis. Microbiological and clinical courses remained unresponsive to apparently appropriate antifungal therapy with azole or polyene derivatives. Both microbiological and clinical outcomes dramatically improved after starting caspofungin therapy. Lack of cross-resistance, lack of toxicity and potent fungicidal activity make caspofungin a very attractive drug in life threatening abdominal candidiasis. The optimal treatment of life threatening candidiasis remains a controversial issue. Because of recent advances in the field, we propose a critical review of the problem of refractory candidiasis.

Abdomen↗
PubMedDate not supplied

Insecticidal and fungicidal compounds from Isatis tinctoria.

Tryptanthrin (1), indole-3-acetonitrile (2) and p-coumaric acid methylester (3) were isolated from the aerial parts of Isatis tinctoria L. The compounds show insecticidal and anti-feedant activity against termites (Reticulitermis santonensis), insect preventive and control activity against larvae of the house longhorn beetle (Hylotrupes bajulus) and fungicidal activity against the brown-rot fungus (Coniophora puteana).

Agaricales↗
PubMed2002

Review of the validation of models used in Federal Insecticide, Fungicide, and Rodenticide Act environmental exposure assessments.

The first activity of the Federal Insecticide. Fungicide, and Rodenticide Act (FIFRA) Environmental Model Validation Task Force, established to increase confidence in the use of environmental models used in regulatory assessments, was to review the literature information on validation of the pesticide root zone model (PRZM) and the groundwater loading effects of agricultural management systems (GLEAMS). This literature information indicates that these models generally predict the same or greater leaching than observed in actual field measurements, suggesting that these models are suitable for use in regulatory assessments. However, additional validation research conducted using the newest versions of the models would help improve confidence in runoff and leaching predictions because significant revisions have been made in models over the years, few of the literature studies focused on runoff losses, the number of studies having quantitative validation results is minimal, and modelers were aware of the field results in most of the literature studies. Areas for special consideration in conducting model validation research include improving the process for selecting input parameters, developing recommendations for performing calibration simulations, devising appropriate procedures for keeping results of field studies from modelers performing simulations to validate model predictions while providing access for calibration simulations, and developing quantitative statistical procedures for comparing model predictions with experimental results.

Agriculture↗
PubMed1983

Testicular atrophy in Gallus domesticus fed acute doses of copper fungicides.

Acute oral toxicity of the copper fungicides, copper sulphate and copper oxychloride, were studied in male Gallus domesticus. The median lethal dose for copper sulphate and copper oxychloride determined were 693 and 1263 mg/kg body weight, respectively. Severe diarrhea and delayed mortality (3 to 6 days) was characteristic of copper oxychloride. Liver weights were nearly doubled in birds fed copper oxychloride and marked dose-dependent testicular atrophy was noticed in both copper sulphate and copper oxychloride fed birds. Mild to severe spermatogenetic arrest concomitant with testicular atrophy was observed. Histochemically, the interstitial (Leydig) cells and seminiferous tubules showed intense accumulation of cholesterol-positive lipids. The degree of lipophilia appeared to be directly proportional to the extent of spermatogenetic arrest, and these results are suggestive of steroidogenic inhibition in the Leydig cells of the atrophied testis.

Animals↗
PubMed1994

Parkinsonism after chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate).

Permanent parkinsonism was observed in a man with chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate). Symptoms developed at 37 years of age, two years after exposure had ceased. To our knowledge, this is the second report on parkinsonism associated with exposure to maneb. Manganese is a well-known parkinsonigen toxin in humans. More recently, it has been shown that dithiocarbamates can also induce extrapyramidal syndromes. The biochemical effects of manganese and dithiocarbamates are reviewed and their possible neurotoxic mechanisms are discussed. Both of these components may have played a role in this case.

Humans↗
PubMed1975

Evaluation of mycobacillin and versicolin as agricultural fungicides. I. Antifungal spectrum and phytotoxicity.

Two antifungal antibiotics, mycobacillin and versicolin, were studied as agricultural fungicides in the control of fungal infection of rice and jute. Mycobacillin is especially active against Piricularia oryzae at a concentration of 10 mug/ml, and versicolin against Colletotrichum gloeosporioides at a concentration of 2.5 mug/ml. Mycobacillin has no adverse effect on germination of seeds and growth of seedlings of rice and jute plants as a concentration of 500ppm, even for prolonged exposure. (24 or 48 hours); in fact, it is stimulatory. On the other hand, versicolin has showed detectable phytotoxicity at 500ppm for prolonged exposure

Antifungal Agents↗
PubMed1988

Cytotoxic, fungicidal nucleosides from blue green algae belonging to the Scytonemataceae.

Tubercidin, toyocamycin, and the corresponding 5'-alpha-D-glucopyranose derivatives of the nucleosides are frequently responsible for much of the cytotoxicity and antimycotic activity associated with extracts of cultured cyanophytes belonging to the family Scytonemataceae. The 5'-alpha-D-glucopyranoses of tubercidin and toyocamycin, for example, are the major cytotoxic and fungicidal nucleosides in Fijian Plectonema radiosum and Hawaiian Tolypothrix tenuis, respectively.

Antifungal Agents↗
PubMed1997

Dihydromaltophilin; a novel fungicidal tetramic acid containing metabolite from Streptomyces sp.

A new tetramic acid containing metabolite, A90931a has been isolated from Streptomyces sp., along with a second factor (A90931b) recently described and known as maltophilin. The structures were determined from spectroscopic data of the isolates and their acetylated products. A90931a was spectroscopically identical to the previously described antibiotic TAN-883b whose structure was not reported. A90931a and A90931b exhibit fungicidal activity against the grape pathogen Plasmopara viticola. Due to its similarity to maltophilin, A90931a has been called dihydromaltophilin.

Anti-Bacterial Agents↗
PubMed2000

On the mechanism of action of the myxobacterial fungicide ambruticin.

The myxobacterial fungicide, ambruticin, kills the yeast, Hansenula anomala, with high efficacy (MIC 0.05 microg/ml), but only when the cells are growing. The earliest effect, observed almost immediately after the addition of the antibiotic, is a transient but substantial increase of intracellular glycerol, followed by an accumulation of triacylglycerols and free fatty acids. At about the time when free fatty acids accumulate, the cells become leaky to low molecular weight compounds. We assume that this leakage kills the cells. The mechanism of action of ambruticin thus appears to be the same as that of the phenylpyrroles, e.g., pyrrolnitrin, viz., interference with osmoregulation.

Antifungal Agents↗
PubMed1998

Fungicidal and binding properties of the natural peptides cecropin B and dermaseptin.

In vitro fungicidal properties of cecropin B and dermaseptin were explored using non-germinating and germinating conidia from Aspergillus flavus, A. fumigatus, A. niger, Fusarium n2oniliforme and F oxysporum. Cecropin B produced LD50 values for germinating A. flavus, A. fumigatus and A. niger conidia of 30, 0.5 and 2.0 microM, respectively, while dermaseptin gave LD50 values of 4.0, 0.05 and 2.0 microM, respectively. Cecropin B produced an LD50 value of 0.2 microM for non-germinating F. moniliforme and F. oxysporum conidia, while dermaseptin did not reduce either as much as 50% at any level tested. LD50 levels for CB were 0.2 and 0.1 microM, respectively, for germinating F. moniliforme and F. oxysporum conidia. Dermaseptin was less effective, giving LD50 values for germinating F. moniliforme and F. oxysporum conidia of 0.3 and 0.8 microM, respectively. Neither peptide reduced conidial viabilities of non-germinating Aspergillus spp. Physicochemical studies indicated cecropin B and dermaseptin bound to ergosterol and cholesterol, conidial wall constituents, but not to chitin or beta-1,3-glucan.

Amino Acid Sequence↗
PubMed1999

Fungistatic and fungicidal activities of murine polymorphonuclear leucocytes against yeast cells of Paracoccidioides brasiliensis.

Recently, a novel culture medium for detecting live yeast cells of Paracoccidioides brasiliensis was developed by Kurita et al. Using this culture medium, murine peritoneal polymorphonuclear leucocytes (PMN) were examined for fungistatic and fungicidal activities against P. brasiliensis yeast cells. The magnitude of the antifungal effect of PMN varied depending upon the fungal isolates used. PMN exhibited a killing effect on P. brasiliensis isolate Bt-4 in 2 h of coculture. In contrast, the other three fungal isolates employed were resistant to killing by PMN. However, PMN considerably suppressed the growth of isolates Tatu and Recife in a long-term assay (approximately 72 h). The growth of isolate Bt-9 was also suppressed by PMN during the first 24 h, but was found to be considerably promoted at 72 h of coculture. Interferon-gamma (IFN-gamma), but not tumour-necrosis factor-alpha, significantly augmented the antifungal activity of PMN. IFN-gamma-treated PMN exhibited a killing effect on isolates Tatu, Recife and Bt-9 after 24 h of coculture, and showed an enhanced killing effect on isolate Bt-4. Contact between PMN and fungal cells was required for PMN to exert the antifungal effect. Our results suggest that PMN, whether activated with cytokines or not, might play a critical role in host resistance in early infection with this fungus by buying time for development of more effective immunologic responses.

Animals↗