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1.  Interaction of Platelets and Anidulafungin against Aspergillus fumigatus 
The combination of platelets and anidulafungin at 0.03 μg/ml significantly (P < 0.05) reduced the germination rate and hyphal elongation in Aspergillus fumigatus compared to those with either anidulafungin only or an untreated control. Platelets decreased the expression of the fks gene, which plays an important role in cell wall synthesis. Our results suggest that human platelets plus anidulafungin might contribute to defense against A. fumigatus.
PMCID: PMC3535898  PMID: 23114752
2.  Potential Antifungal Effects of Human Platelets against Zygomycetes In Vitro 
The Journal of infectious diseases  2009;200(7):1176-1179.
Zygomycosis is increasingly recognized in immunocompromised hosts. We investigated whether platelets become activated after contact with Zygomycetes and adhere to conidial and hyphal structures using immunofluorescence. The platelets’ influence on fungal viability was evaluated by assessing hyphal elongation and hyphal damage. Platelets became activated and strongly adhered to conidia and hyphae of Zygomycetes. Platelets induced time dependent damage to hyphae and significantly reduced (P < .05) hyphal elongation. We found that platelets possess antifungal capacities against Zygomycetes based on granule dependent mechanisms and significantly reduce fungal growth and spread, both of which are of major importance in evolving invasive disease.
PMCID: PMC3017871  PMID: 19698079
3.  Interaction of 5-hydroxytryptamine (serotonin) against Aspergillus spp. in vitro 
This study examined the direct interaction of serotonin (5-hydroxytryptamine (5-HT)) with Aspergillus species. Accumulation of 5-HT in aspergilli was investigated by immunofluorescence staining and laser confocal scanning microscopy. The influence of 5-HT on fungal ergosterol content, cell membrane integrity, fungal growth and hyphal elongation was determined. 5-HT was localised in the cytoplasm of Aspergillus spp., as 5-HT fluorescent signals appeared after 30 min at 4°C and in the presence of inhibitors of oxidative phosphorylation. 5-HT treatment of Aspergillus spp. significantly affected ergosterol synthesis, fungal cell membrane integrity and hyphal elongation (P < 0.05). 5-HT treatment for 4 h resulted in a lag of re-growth (post-antifungal effect). In conclusion, our findings suggest that 5-HT affects hyphal growth and diminishes fungal cell membrane integrity.
PMCID: PMC3010239  PMID: 17276041
Serotonin; Aspergillus spp.; Ergosterol; Platelets
4.  Human Platelets Attenuate Aspergillus Species via Granule-Dependent Mechanisms 
The Journal of infectious diseases  2008;198(8):1243-1246.
Using laser scanning microscopy, we investigated whether platelets are capable of internalizing Aspergillus conidia and examined Aspergillus-platelet adherence. The influence of platelets on fungal growth was evaluated by assessing galactomannan (GM) release, hyphal elongation, and colony size. A secretion assay with [3H]-serotonin (5-hydroxytryptamine [5-HT]) was performed. Exposure to platelets resulted in significantly decreased GM release (P<.05), hyphal elongation (P<.001), colony size, pig-mentation, and 5-HT release (P<.05). A lack of antifungal effects was observed with the microfilament inhibitor cytochalasin D. Platelets attenuate the virulence of Aspergillus species in vitro on the basis of granule-dependent effects.
PMCID: PMC2980866  PMID: 18752432
5.  In Vitro Activity of Isavuconazole against Aspergillus Species and Zygomycetes According to the Methodology of the European Committee on Antimicrobial Susceptibility Testing▿  
We evaluated the MICs of isavuconazole (ISAV) against 96 isolates of Aspergillus species and 36 zygomycetes according to the methodology of the European Committee on Antimicrobial Susceptibility Testing. In addition, the in vitro activity was obtained for hyphal inocula. ISAV exhibited good antifungal activity against the tested isolates with the exception of Aspergillus niger and Mucorales. The in vitro activity of ISAV was comparable to that of voriconazole aside from Mucorales.
PMCID: PMC2663115  PMID: 19164153
6.  In Vitro Activities of Various Antifungal Drugs against Aspergillus terreus: Global Assessment Using the Methodology of the European Committee on Antimicrobial Susceptibility Testing▿  
This study presents in vitro susceptibility data for clinical (n = 48) and environmental (n = 31) isolates of Aspergillus terreus against nine antifungal agents. The methodology of the European Committee on Antimicrobial Susceptibility Testing was applied. Posaconazole and anidulafungin had the lowest and amphotericin B the highest MICs. No differences in susceptibility patterns were observed between environmental and clinical isolates.
PMCID: PMC2630662  PMID: 19064891
7.  Activities of Antifungal Agents against Yeasts and Filamentous Fungi: Assessment according to the Methodology of the European Committee on Antimicrobial Susceptibility Testing ▿  
Antimicrobial Agents and Chemotherapy  2008;52(10):3637-3641.
We compared the activities of antifungal agents against a wide range of yeasts and filamentous fungi. The methodology of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for yeasts and spore-forming molds was applied; and a total of 349 clinical isolates of Candida spp., other yeast species, Aspergillus spp., and nondermatophyte non-Aspergillus spp. were investigated. The average geometric mean (GM) of the MICs of the various drugs for Candida spp. were as follows: amphotericin B (AMB), 0.55 μg/ml; liposomal amphotericin B (l-AMB); 0.35 μg/ml; itraconazole (ITC), 0.56 μg/ml; voriconazole (VRC), 0.45 μg/ml; posaconazole (POS), 0.44 μg/ml; and caspofungin (CPF), 0.45 μg/ml. The data indicated that the majority of Candida spp. were susceptible to the traditional and new antifungal drugs. For Aspergillus spp., the average GM MICs of AMB, l-AMB, ITC, VRC, POS, and CPF were 1.49 μg/ml, 1.44 μg/ml, 0.65 μg/ml, 0.34 μg/ml, 0.25 μg/ml, and 0.32 μg/ml, respectively. For the various zygomycetes, the average GM MICs of AMB, l-AMB, ITC, and POS were 1.36 μg/ml, 1.42 μg/ml, 4.37 μg/ml, and 1.65 μg/ml, respectively. Other yeastlike fungi and molds displayed various patterns of susceptibility. In general, the minimal fungicidal concentrations were 1 to 3 dilutions higher than the corresponding MICs. POS, AMB, and l-AMB showed activities against a broader range of fungi than ITC, VRC, and CPF did. Emerging pathogens such as Saccharomyces cerevisiae and Fusarium solani were not killed by any drug. In summary, the EUCAST data showed that the in vitro susceptibilities of yeasts and filamentous fungi are variable, that susceptibility occurs among and within various genera and species, and that susceptibility depends on the antifungal drug tested. AMB, l-AMB, and POS were active against the majority of pathogens, including species that cause rare and difficult-to-treat infections.
PMCID: PMC2565893  PMID: 18694949
8.  Establishing In Vitro-In Vivo Correlations for Aspergillus fumigatus: the Challenge of Azoles versus Echinocandins▿  
Antimicrobial Agents and Chemotherapy  2008;52(10):3504-3511.
Two clinical isolates of Aspergillus fumigatus, designated AT and DK, were recently obtained from patients failing caspofungin and itraconazole therapy, respectively. The isolates were tested by microdilution for susceptibility to itraconazole, voriconazole, posaconazole, ravuconazole, and caspofungin and by Etest for susceptibility to amphotericin B and caspofungin. Susceptibility testing documented that the DK isolate was azole resistant (itraconazole and posaconazole MICs, >4 μg/ml; voriconazole MIC, 2 μg/ml; ravuconazole MIC, 4 μg/ml), and the resistance was confirmed in a hematogenous mouse model, with mortality and the galactomannan index as the primary and secondary end points. Sequencing of the cyp51A gene revealed the M220K mutation, conferring multiazole resistance. The Etest, but not microdilution, suggested that the AT isolate was resistant to caspofungin (MIC, >32 μg/ml). In the animal model, this isolate showed reduced susceptibility to caspofungin. Sequencing of the FKS1 gene revealed no mutations; the enzyme retained full sensitivity in vitro; and investigation of the polysaccharide composition showed that the β-(1,3)-glucan proportion was unchanged. However, gene expression profiling by Northern blotting and real-time PCR demonstrated that the FKS gene was expressed at a higher level in the AT isolate than in the susceptible control isolate. To our knowledge, this is the first report to document the presence of multiazole-resistant clinical isolates in Denmark and to demonstrate reduced susceptibility to caspofungin in a clinical A. fumigatus isolate with increased expression of the FKS gene. Further research to determine the prevalence of resistance in A. fumigatus worldwide, and to develop easier and reliable tools for the identification of such isolates in routine laboratories, is warranted.
PMCID: PMC2565905  PMID: 18644959
9.  Posaconazole Enhances the Activity of Amphotericin B against Hyphae of Zygomycetes In Vitro▿  
The in vitro activity of posaconazole plus amphotericin B against conidia and hyphae of 30 clinical zygomycetes was investigated. The combination of posaconazole with amphotericin B was found to be significantly more synergistic (40%) against hyphae (P < 0.05) than against conidia (10%). Antagonism was not observed.
PMCID: PMC2443899  PMID: 18458135
10.  Susceptibility Testing of Anidulafungin and Voriconazole Alone and in Combination against Conidia and Hyphae of Aspergillus spp. under Hypoxic Conditions▿  
MICs and fractional inhibitory concentrations were evaluated for anidulafungin and voriconazole alone and in combination against conidia and hyphae under hypoxic (1% oxygen-5% CO2-94% nitrogen) conditions against 31 Aspergillus isolates. Anidulafungin exhibited excellent activity against conidia and hyphae of Aspergillus spp. The visual reading of the MIC for anidulafungin was optimal under hypoxic conditions.
PMCID: PMC2346651  PMID: 18347112
11.  Potential Basis for Amphotericin B Resistance in Aspergillus terreus▿  
This study investigated the basis for intrinsic amphotericin B (AMB) resistance in Aspergillus terreus. The ergosterol content, cell wall composition, and lipid peroxidation level had no influence on AMB resistance. The level of catalase production in A. terreus was significantly higher than that in A. fumigatus (P < 0.05). This higher-level production may contribute to AMB resistance in A. terreus since oxidative damage has been implicated in AMB action.
PMCID: PMC2292529  PMID: 18268082
12.  Posaconazole Enhances the Activity of Amphotericin B against Aspergillus Hyphae In Vitro▿  
The MICs and fractional inhibitory concentrations of posaconazole (POS) and voriconazole (VRZ), alone and in combination with amphotericin B (AMB), for the conidia and hyphae of 100 Aspergillus isolates were evaluated. POS-AMB had more synergistic activity against hyphae (75% of isolates) than VRZ-AMB (37%) and significantly more synergistic activity against hyphae than against conidia (12%).
PMCID: PMC1797736  PMID: 17116665

Results 1-12 (12)