Elucidating population structure and levels of genetic diversity and recombination is necessary to understand the evolution and adaptation of species. Candida albicans is the second most frequent agent of human fungal infections worldwide, causing high-mortality rates. Here we present the genomic sequences of 182 C. albicans isolates collected worldwide, including commensal isolates, as well as ones responsible for superficial and invasive infections, constituting the largest dataset to date for this major fungal pathogen. Although, C. albicans shows a predominantly clonal population structure, we find evidence of gene flow between previously known and newly identified genetic clusters, supporting the occurrence of (para)sexuality in nature. A highly clonal lineage, which experimentally shows reduced fitness, has undergone pseudogenization in genes required for virulence and morphogenesis, which may explain its niche restriction. Candida albicans thus takes advantage of both clonality and gene flow to diversify.

No abstract

No abstract

Resistance to triazoles in Aspergillus fumigatus has been reported in azole-naive patients in Europe, Asia, Australia and North America. This resistance has been linked to fungicide-driven mutations in the cyp51A gene and its promoter region. We investigated the presence of environmental azole-resistant A. fumigatus strains related to the use of azole fungicides in Colombia. Soil samples were collected from flower beds, flower fields and public gardens from the outskirts, suburbs and city centre of Bogotá. Out of the 86 soil samples taken, 17 (19.8%) grew A. fumigatus of whom eight (9.3%) contained 40 strains able to grow on azole-containing itraconazole and/or voriconazole supplemented media. All but one triazole-resistant strains were isolated from soil samples collected from flower fields and flower beds (39/40). Importantly, the majority had the TR46/Y121F/T289A, TR34/L98H, and TR53 molecular resistance mechanisms and one azole resistant strain had a wild-type cyp51A gene. Soil samples from flower fields and beds contained 4 azole fungicides (penconazole, difenoconazole, tetraconazole and tebuconazole) above the limit of detection. Our findings underline the need for extensive investigations to determine azole-resistant A. fumigatus prevalence in both clinical and environmental samples in other regions of Latin America.

No abstract

We report an 8% prevalence of itraconazole resistance in CF patients in our centre, mostly driven by TR/L98H (6%). Our data confirm that TR/L98H occurs in France and can be highly prevalent in CF patients.

These findings demonstrate the critical role of residue 193 in Erg3p function and azole resistance. We suggest that this attenuated in vivo virulence phenotype could be linked to lower potential for hyphal growth. Taken together, our findings highlight the fact that erg3 mutants must be considered in future studies aiming at investigating azole antifungal drug resistance.

We report a case of disseminated Scedosporium/Pseudallescheria infection due to Pseudallescheria boydii sensu stricto after lung transplantation in a patient with cystic fibrosis. Dissemination occurred under voriconazole. Despite surgery and combination therapy with voriconazole, caspofungin, and terbinafine, the patient died 8 months after transplantation. Previously reported cases are reviewed. CASE REPORTA 37-year-old woman suffering from cystic fibrosis (CF) was admitted to our institution in April 2008 for double-lung transplantation. Her medical history included diabetes mellitus since 2002 and more than 10 years of airway colonization with Aspergillus fumigatus and Scedosporium/Pseudallescheria. Starting in 2006, and while awaiting transplantation, she received oral voriconazole (250 mg, twice a day). Her postoperative course was relatively uncomplicated except for cytomegalovirus (CMV) infection due to a mismatch at the time of transplantation in spite of valganciclovir prophylactic treatment (900 mg/day). The immunosuppressive regimen included tacrolimus (therapeutic range, 12 to 13.5 ng/ml), mycophenolate mophetil (750 mg/day), and prednisone (37.5 mg/day). Oral voriconazole was continued as a long-term posttransplantation prophylaxis (250 mg twice a day). A fungal culture of a bronchial secretion obtained the day after transplantation was positive for a filamentous fungus routinely identified as Scedosporium apiospermum/P. boydii (isolate I), but several other respiratory specimens obtained over the following weeks were negative. The patient was discharged from the hospital on day 45 after transplantation, still taking voriconazole. The voriconazole serum levels, checked regularly (1.06, 1.96, and 1.69 mg/liter on days 26, 36, and 50, respectively) were within therapeutic limits (1 to 2.5 mg/liter) except for two occasions (0.16 and 0.35 mg/liter on days 18 and 64, respectively).In June (day 70), she presented at our hospital with nodules on her legs that had appeared 2 weeks previously. On examination, the nodules were fibrous, dermo-hypodermic, measuring 1 to 2 cm in diameter, and slightly pigmented on the surface. A biopsy was performed. Histopathological microscopic examination (Gomori-Grocott and periodic acid-Schiff stainings) revealed an inflammatory infiltrate along with several branched and septate hyaline hyphae (fungal cultures were not performed). Continuation of voriconazole in association with a reduced dose of corticosteroid was associated with clinical improvement. However, 3 weeks later, a new biopsy was performed and septate hyphae were again seen on direct examination. A fungal culture of this biopsy specimen was positive for S. apiospermum/P. boydii (isolate II). At this time, the results for chest computed tomography (CT) were unremarkable, no sign of dissemination was noted on brain CT, and the nodules disappeared over the following weeks.All the while, positive CMV DNAemia was still detected in spite of successive curative treatments with per os valganciclovir (1,800 mg/day fro...