Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology最新文献

We examined fast atom bombardment mass spectra (FAB-MS) of 29 clinical isolates of Aspergillus, from five pathogenic species, for the presence of phthioic acid anions (m/z 395.6) when grown at 37 degrees C. Phthioic acid was detected in only one of 12 A. fumigatus, three of nine A. terreus and one of four A. niger isolates. Phthioic acid is unlikely to be a major pathogenicity determinant of Aspergillus.

The echinocandins and pneumocandins are lipopeptide antifungal agents that inhibit the synthesis of 1,3-beta-D-glucan, an essential cell wall homopolysaccharide found in many pathogenic fungi. Compounds with this fungal-specific target have several attractive features: lack of mechanism-based toxicity, potential for fungicidal activity and activity against strains with intrinsic or acquired resistance mechanisms for existing antimycotics. Semi-synthetic analogues of naturally occurring lipopeptides are currently in clinical trials with the aim of treating systemic candidiasis and aspergillosis. Thus a fuller understanding of the target enzyme and its inhibition by these compounds should be useful for epidemiological and other clinical studies. Although it has been long known that lipopeptides inhibit fungal glucan synthase activity both in cell extracts and in whole cells, the genetic and biochemical identification of the proteins involved has been accomplished only recently. We now know that in Saccharomyces cerevisiae, glucan synthase is a heteromeric enzyme complex comprising one large integral membrane protein (specified by either FKS1 or by FKS2) and one small subunit more loosely associated with the membrane (specified by RHO1). Additional components may also be involved. The heteromeric enzyme complex containing Fks1p constitutes the majority of the activity found in vegetatively growing cells in this organism. The FKS2 gene product is needed for sporulation. Lipopeptides affect the function of the Fksp component from either FKS gene. The current model for interaction and regulation of these components in S. cerevisiae and the application to Candida albicans and other pathogenic fungi are discussed in this review.

A retrospective study was conducted in France to investigate Fusarium infections which are now recognized as emerging opportunistic infections. The clinical and mycological findings for 31 cases diagnosed between 1984 and 1993 by members of the French Groupe d'Etudes des Mycoses Opportunistes were analysed. All suffered from haematological disease, most often acute leucaemia (n = 19). Twenty-two had received cytostatic chemotherapy and ten had undergone bone marrow transplantation. Prolonged aplasia and pancytopenia were present in 18 and 11 patients, respectively. Skin (61%) and blood (42%) were the sites most frequently involved. Fusarium solani (n = 7), Fusarium oxysporum (n = 7), Fusarium verticilloides (n = 7) were the species most frequently isolated. Nine antifungal treatments were used, associated with colony-stimulating factors in five cases. None was unambiguously superior to all the others. The overall mortality was 51.6% with a specific mortality > or = 25.8%. The disseminated form of the infection was associated with poor prognosis (P < 0.02) whereas improving granulocyte count improved prognosis (P < 0.001). More aggressive cytostatic regimens used for patients with haematological malignancies have favoured the emergence of Fusarium infections. As prognosis is closely correlated with neutrophil recovery, the promising results obtained with the use of colony-stimulating factors should be further evaluated.

Protein antigens of Penicillium marneffei prepared during the yeast and mould phases of in vitro growth were analyzed by gel electrophoresis and immunoblot assay. More than 20 yeast phase proteins were detected by Coomassie staining; among these, at least 10 reacted with IgG in the pooled sera of 28 AIDS patients with penicilliosis. Four immunogenic proteins of 200, 88, 54 and 50 kDa were produced in large quantity during the deceleration and early stationary phases of growth. When these proteins were reacted with individual sera derived from 33 AIDS patients with penicilliosis, reactivities to the 200, 88, 54 and 50 kDa protein were detected in 72.7, 93.9, 60.6 and 57.6%, respectively. The bands of 88, 54 and 50 kDa gave strong reactions with about a half of serum samples. In one serum derived from an AIDS patient, reactivities to the 54 and 50 kDa proteins could be strongly detected two months before the definite diagnosis by fungal culture. Protein components from the mould form were of lower yield and gave weaker signal in immunoblot analysis. These results indicate that at least two yeast-phase immunoreactive proteins (54 and 50 kDa) are relatively specific to the P. marneffei infection, thereby suggesting its potential for clinical application to the diagnosis of this emerging disease.

Emergence of resistance of Candida albicans to antifungal triazoles is increasingly recognized as an important cause of refractory mucosal candidiasis in HIV-infected patients. Recently, CDR1, which is thought to be analogous to the human MDR-1 P-glycoprotein, has been cloned in C. albicans. It has been proposed that its expression is partially responsible for fluconazole resistance in C. albicans. This gene is characterized by the presence of an ATP binding cassette (ABC) region and is distinct from the BENr gene which does not encode such a functional domain. As the molecular basis for fluconazole resistance appears to be multifactorial, we considered that there may be other ATP binding cassette-containing MDR genes that may potentially contribute to antifungal azole resistance in C. albicans. We therefore sought to identify potential target sequences that may be derived from candidate genes that share homology with the ATP binding cassette region of the human MDR-1 P-glycoprotein. Degenerate oligonucleotide primers based on the known sequence from the ATP binding cassette region of the human MDR-1 P-glycoprotein were used to amplify PCR products within the range of 100 bp in length from C. albicans isolates (3 fluconazole-susceptible and 3 fluconazole-resistant). Sequence analysis of individually subcloned PCR products, derived from the six isolates revealed 34 sequences in total. The results of our study identified 14 clones (with at least one per isolate) with a high degree of homology to the ATP binding cassette of the human MDR-1 P-glycoprotein. The BLAST search did not disclose homology of these new sequences to the C. albicans CDR1 gene, suggesting that C. albicans may possess more than one MDR-like gene. We conclude that C. albicans may possess one or more additional genes encoding ATP binding cassette MDR-like proteins that are distinct from CDR 1 and which could participate in the development of fluconazole resistance.