Acremonium kiliense: case report and review of published studies.

Changes in the spectrum of clinically important fungal infection have been observed in recent years. Acremonium species has been responsible for eumycotic mycetomas but has also been increasingly implicated in systemic fungal diseases. A case of Acremonium kiliense fungemia with proven involvement of the lungs in an allogeneic hematopoietic stem cell patient is reported. A high-resolution computed tomography scan of the lungs showed nodules in both lungs. Multiple cultures of blood demonstrated narrow septate hyphae, cylindrical conidia, and solitary tapering phialides and microconidia that remained grouped in slimy heads. The isolate was identified as A. kiliense based on its morphological characteristics and DNA sequence analysis. Susceptibility testing of the clinical isolate was performed to four antifungal agents. Amphotericin B, fluconazole and itraconazole were found to be inactive in vitro against the isolate; however, it was found to be sensitive to voriconazole. This last drug was indicated, and a high-resolution computed tomography scan of the lungs was normal after 10 days. One year later, the patient was free of symptoms and her blood culture was negative for fungi. Thus, voriconazole was effective in treatment for life-threatening A. kiliense infections. In this work, we performed an overview of worldwide clinical infections caused by A. kiliense.

Spectrum of clinically relevant Acremonium species in the United States.

Some species in the polyphyletic fungal genus Acremonium are important opportunist pathogens. Determining the actual spectrum of species and their incidence in the clinical setting, however, has long been hampered because of the difficulties encountered in phenotypic species-level identification. The goal of this study was to re-identify a large number of clinical isolates morphologically and to confirm the identifications by comparing sequences of the internal transcribed spacer region of the rRNA gene of these isolates to those of type or reference strains of well-known Acremonium species. Of the 119 isolates referred to a United States reference laboratory under the name Acremonium, only 75 were identified morphologically as belonging to that genus. The remainder (44 isolates) were identified as belonging to other morphologically similar genera. The Acremonium clinical isolates were related to species of Hypocreales, Sordariales, and of an incertae sedis family of ascomycetes, Plectosphaerellaceae. A total of 50 of the 75 Acremonium isolates (67%) could be identified by molecular means, the prevalent species being Acremonium kiliense (15 isolates), A. sclerotigenum-A. egyptiacum (11 isolates), A. implicatum (7 isolates), A. persicinum (7 isolates), and A. atrogriseum (4 isolates). One of the most interesting findings of our study was that we identified several species among this large collection of clinical isolates that had not previously been reported from human infections, and we failed to confirm other Acremonium species, such as A. potronii, A. recifei, and A. strictum, that had been considered significant. The most common anatomic sites for Acremonium isolates were the respiratory tract (41.3%), nails (10.7%), and the eye (9.3%). Antifungal susceptibility testing demonstrated high MICs for all agents tested, except for terbinafine. Since numerous isolates could not be identified, we concluded that the list of opportunistic Acremonium species is far from be complete and that a considerable number of additional species will be discovered.

A homologue of the Aspergillus velvet gene regulates both cephalosporin C biosynthesis and hyphal fragmentation in Acremonium chrysogenum.

The Aspergillus nidulans velvet (veA) gene encodes a global regulator of gene expression controlling sexual development as well as secondary metabolism. We have identified the veA homologue AcveA from Acremonium chrysogenum, the major producer of the beta-lactam antibiotic cephalosporin C. Two different disruption strains as well as the corresponding complements were generated as a prelude to detailed functional analysis. Northern hybridization and quantitative real-time PCR clearly indicate that the nucleus-localized AcVEA polypeptide controls the transcriptional expression of six cephalosporin C biosynthesis genes. The most drastic reduction in expression is seen for cefEF, encoding the deacetoxycephalosporine/deacetylcephalosporine synthetase. After 120 h of growth, the cefEF transcript level is below 15% in both disruption strains compared to the wild type. These transcriptional expression data are consistent with results from a comparative and time-dependent high-performance liquid chromatography analysis of cephalosporin C production. Compared to the recipient, both disruption strains have a cephalosporin C titer that is reduced by 80%. In addition to its role in cephalosporin C biosynthesis, AcveA is involved in the developmentally dependent hyphal fragmentation. In both disruption strains, hyphal fragmentation is already observed after 48 h of growth, whereas in the recipient strain, arthrospores are not even detected before 96 h of growth. Finally, the two mutant strains show hyperbranching of hyphal tips on osmotically nonstabilized media. Our findings will be significant for biotechnical processes that require a defined stage of cellular differentiation for optimal production of secondary metabolites.

Morphologic criteria for the preliminary identification of Fusarium, Paecilomyces, and Acremonium species by histopathology.

Nontraditional human pathogenic fungi, including Fusarium, Paecilomyces, and Acremonium species, have been increasingly documented as agents of infection in immunocompromised patients and, occasionally, in normal hosts. Although definitive identification of these fungi requires culture, they often can be identified provisionally in tissue sections by a combination of histologic features, including hyaline septate hyphae and characteristic reproductive structures known as phialides and phialoconidia. These morphologic characteristics, although familiar to mycologists, are easily overlooked by histopathologists; as a result, Fusarium species and Paecilomyces lilacinus are frequently misidentified in tissue sections as Aspergillus or Candida species. We identified 19 culture-proved cases of infection with species of Fusarium, Paecilomyces, or Acremonium; retrospectively reviewed histologic specimens stained by routine hematoxylin and eosin, Gomori methenamine silver, and/or periodic acid-Schiff stains; and delineated morphologic criteria that will help pathologists make a preliminary identification of these fungi by histopathology. Adventitious sporulation was found in 9 of 9 infections caused by Paecilomyces species, 7 of 10 infections caused by Fusarium species, and in the single case of infection caused by Acremonium strictum. Histologic recognition of these morphologies may help clinicians select appropriate initial antifungal treatment and manage the infection.