Rabbits that had been infected intravenously with conidiospores of Aspergillus fumigatus were used as sources of antibody for screening a lambda phage cDNA expression library. The cDNA was derived from A. fumigatus mRNA that had been extracted from newly formed, germling hyphae. Thirty-six antigens were identified using antisera from six rabbits. Though many of these antigens were expected to be intracellular proteins because their genes did not encode a signal sequence, the antisera showed consistently a stronger immunoblot reaction with a cell fraction enriched for the fungal cell wall than with a fraction of predominantly intracellular components. Antibodies to eight antigens, including the glycosylhydrolase Asp f 16, were produced by more than one rabbit. In current vaccine studies, Asp f 16 is the only single antigen which has been reported to be capable of inducing protection against invasive aspergillosis in mice. Enolase and Aspergillus HSP90 were detected also; their homologues in Candida albicans have been tested as vaccines and have been reported to provide a partially protective response against invasive candidiasis in mice. The Aspergillus antigens reported here may have value both in diagnostic tests for different forms of aspergillosis and as vaccine candidates for protection against invasive disease.
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http://dx.doi.org/10.1128/IAI.73.8.4704-4713.2005 | DOI Listing |
Sci Rep
December 2024
Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Weiwu Road No. 7, Zhengzhou, 450003, Henan, China.
To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) and galactomannan (GM) testing in invasive pulmonary aspergillosis (IPA) and to compare mNGS with other diagnostic approaches (serum/bronchoalveolar lavage fluid (BALF)-GM and conventional microbiological tests (CMTs) including sputum smears and culture, BALF fungal culture, and bronchial brushing). In all, 237 patients were enrolled in this retrospective study, including 120 patients with IPA and 117 with non-IPA pulmonary infections treated at Henan Provincial People's Hospital between June 2021 and February 2024. The diagnostic performance of mNGS was compared to conventional diagnostic methods including serum GM, BALF-GM, sputum smear microscopy, sputum culture, bronchial brushings, and BALF culture.
View Article and Find Full Text PDFJ Fungi (Basel)
December 2024
School of Pharmacy, University of Connecticut, 69, North Eagleville Road, Storrs, CT 06269, USA.
Changes to antifungal therapy (AFT) in invasive aspergillosis (IA) may occur due to intolerance, side effects, drug interactions, or lack of response. We describe AFT change patterns in IA patients. This was a US claims data study.
View Article and Find Full Text PDFJ Fungi (Basel)
December 2024
Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand.
Due to the high morbidity and mortality rates of invasive aspergillosis (IA) and the importance of early IA detection for successful treatment and subsequent outcome, this study aimed to determine a time course of detectable antigen in a mouse model of IA and correlate it with tissue invasion by using two novel monoclonal antibodies, 1D2 and 4E4, that can be used to detect the -derived glycoproteins. Immunocompromised mice were randomly divided into five groups: uninfected control, and inoculation with conidia from , , and . Conidia (2 × 10 cells/mL) were administered intravenously via tail vein injection.
View Article and Find Full Text PDFJ Fungi (Basel)
November 2024
Department of Chemistry, Colorado State University, 1801 Campus Delivery, Fort Collins, CO 80523, USA.
In the last decade, pulmonary fungal infections such as invasive pulmonary aspergillosis (IPA) have increased in incidence due to the increased number of immunocompromised individuals. This increase is especially problematic when considering mortality rates associated with IPA are upwards of 70%. This high mortality rate is due to, in part, the length of time it takes to diagnose a patient with IPA.
View Article and Find Full Text PDFJ Fungi (Basel)
November 2024
Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin 9016, New Zealand.
is intrinsically resistant to the widely used antifungal fluconazole, and therapeutic failure can result from acquired resistance to voriconazole, the primary treatment for invasive aspergillosis. The molecular basis of substrate specificity and innate and acquired resistance of to azole drugs were addressed using crystal structures, molecular models, and expression in of the sterol 14α-demethylase isoforms AfCYP51A and AfCYP51B targeted by azole drugs, together with their cognate reductase AfCPRA2 and AfERG6 (sterol 24-C-methyltransferase). As predicted by molecular modelling, functional expression of CYP51A and B required eburicol and not lanosterol.
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