Fungal pathogens cause disease in plant and animal hosts. The extent to which infection mechanisms are conserved between both classes of hosts is unknown. We present a dual plant-animal infection system based on a single strain of Fusarium oxysporum, the causal agent of vascular wilt disease in plants and an emerging opportunistic human pathogen. Injection of microconidia of a well-characterized tomato pathogenic isolate (isolate 4287) into the lateral tail vein of immunodepressed mice resulted in disseminated infection of multiple organs and death of the animals. Knockout mutants in genes encoding a mitogen-activated protein kinase, a pH response transcription factor, or a class V chitin synthase previously shown to be implicated in virulence on tomato plants were tested in the mouse model. The results indicate that some of these virulence factors play functionally distinct roles during the infection of tomato plants and mice. Thus, a single F. oxysporum strain can be used to study fungal virulence mechanisms in plant and mammalian pathogenesis.
Infections caused by dermatophytes are probably the most common communicable fungal diseases affecting humans. Although a wide variety of both topically and systemically administered compounds with activities against these fungi are available, some of these infections are still difficult to resolve completely and remissions and relapses are often observed (3, 9). Remissions and relapses are more likely due to the inability of the antifungal drug to penetrate the site of infection rather than to the intrinsic resistance of the fungus. In recent years there has been growing interest in the development of a reference method for in vitro antifungal susceptibility testing of dermatophytes. The studies that have been described in the literature (1,8,11,12,14) are based on slight modifications of the broth macro-and microdilution techniques for molds recommended by the NCCLS (document M38-P) (13). However, these methods may not be the most practical procedures for use in the routine clinical laboratory, mainly due to the need for the subjective determination of endpoints.The addition of an oxidation-reduction colorimetric indicator, such as Alamar Blue, which changes from blue to red in the presence of metabolically active growing organisms, has been shown to facilitate the reading of MIC endpoints (4, 7) and could be an alternative to broth macro-and microdilution techniques for molds for use in a general laboratory. The Sensititre YeastOne Colorimetric Antifungal panel (Trek Diagnostic Systems Ltd., East Grinstead, United Kingdom) is a commercial microdilution plate that is already available and that contains dried serial dilutions of five antifungal agents (amphotericin B, flucytosine, fluconazole, itraconazole, and ketoconazole) in a diluent with Alamar Blue. The aim of this study was to compare the in vitro activities of four antifungals both by tests with the Sensititre YeastOne panel and by an adaptation of the NCCLS broth microdilution method, performed independently.Sensititre method. The Sensititre YeastOne test panels were provided by IZASA S.A. (Barcelona, Spain). A total of 49 clinical isolates belonging to six of the most common species of dermatophytes were tested (Table 1). Paecilomyces variotii ATCC 36257 was included as a reference strain. The fungi were subcultured on potato dextrose agar, and stock inoculum suspensions were prepared according to the recommendations of the NCCLS (13). This suspension was then adjusted with a spectrophotometer to 65 to 70% transmittance for dermatophytes and to 74 to 76% transmittance for P. variotii at a wavelength of 530 nm. The working suspension was made by dilution of the suspensions 1:100 in RPMI 1640 to produce the final test concentration of the inoculum. Aliquots of 100 l of the diluted suspension were inoculated into the wells with antifungals and the growth control well (containing only diluent and colorimetric indicator) with a multichannel pipette. The concentrations of the amphotericin B, itraconazole, and ketoconazole dilutions ranged from 0.008 to 16 g...
We have evaluated the efficacy of voriconazole (VRC) in a murine model of systemic infection by Scedosporium apiospermum. The survival of mice treated with VRC at 5, 20, or 40 mg/kg/day was greater than that of the control group (P < 0.0009). VRC reduced the tissue burden in the spleen and brain (P < 0.001 in both organs) in comparison with that of the control group.
The in vitro activities of eight antifungal drugs against 50 isolates of basidiomycetous yeasts were determined by a microdilution method. In general fluconazole and micafungin were inactive. Terbinafine was active only against Sporobolomyces salmonicolor. The activities of the other antifungals were variable and depended on the species tested. The new triazoles showed the lowest MICs, but amphotericin B and itraconazole were the only drugs active against Cryptococcus albidus.Basidiomycetous yeasts are anamorphs (asexual states) of members of jelly fungi (Tremellales) or smuts (Ustilaginales). Some of these yeasts, such as Cryptococcus neoformans and Malassezia spp., are well-known human pathogens. However, many other species are also able to cause human infections, mainly in immunosuppressed patients. Among these, Cryptococcus albidus, Cryptococcus laurentii, Sporobolomyces salmonicolor, Rhodotorula glutinis, and, more commonly, Trichosporon asahii have been reported to cause severe infections (1,4,10,12,19,23). In general the most common treatment for yeast infections is based on the use of amphotericin B (AMB) and fluconazole (FLC). However, against infections caused by the five above-mentioned species, these drugs have repeatedly failed (3,5,7,12,13,21). Such a limitation, associated with AMB toxicity, determines the interest in evaluating the potential antifungal role of the new azoles and echinocandins. Although some of these species have been tested in vitro, only the responses of a reduced number of isolates are known (6,24). Trichosporon has received the most attention (2, 3, 21-23), but in most studies the strains tested were identified as Trichosporon beigelii, which is a not valid name, and so it is not known which current species were actually tested.In this study we have evaluated the in vitro activity of eight antifungal drugs against the five opportunistic species mentioned above. Although a reference method for testing these species does not exist, we have used M27-A2 (17), which has been shown to be very useful for testing the more-common yeasts.A total of 50 isolates were tested (10 species each of C. albidus, C. laurentii, R. glutinis, S. salmonicolor, and T. asahii). Most of them are clinical isolates provided by the BCCM/ IHEM Biomedical Fungi/Yeast collection or Centraalbureau voor Schimmelcultures. The isolates were stored lyophilized and were subcultured on Sabouraud dextrose agar for the study. T. asahii, S. salmonicolor, and R. glutinis were incubated at 35°C for 24 to 72 h, and C. albidus and C. laurentii were incubated at 30°C for 48 to 72 h. Candida krusei ATCC 6258 and Candida parapsilosis ATCC 22019 were included in each batch of tests as a quality control.Antifungal agents were obtained as pure powders. AMB (USP, Rockville, Md.), albaconazole (ABC; J. Uriach & Cía, Barcelona, Spain), voriconazole (VRC; Pfizer Inc., Madrid, Spain), itraconazole (ITC; Janssen Pharmaceutica, Beerse, Belgium), ravuconazole (RVC; Bristol-Myers Squibb Company, New Brunswick, N.J.), and terbinafine (TBF...
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