Blastomycosis acquired occupationally during prairie dog relocation--Colorado, 1998.
(1/211)
On August 31, 1998, two suspected cases of fungal pneumonia were reported to the Boulder County (Colorado) Health Department (BCHD). Both patients were immunocompetent, otherwise healthy adults working for the City of Boulder Open Space (CBOS) program on a prairie dog relocation project. This report summarizes the epidemiologic investigation by BCHD, the Colorado Department of Public Health and Environment, and CDC; the findings indicate that these two persons acquired blastomycosis in Colorado, which is outside the area where the disease is endemic. (+info)
Targeted gene disruption reveals an adhesin indispensable for pathogenicity of Blastomyces dermatitidis.
(2/211)
Systemic fungal infections are becoming more common and difficult to treat, yet the pathogenesis of these infectious diseases remains poorly understood. In many cases, pathogenicity can be attributed to the ability of the fungi to adhere to target tissues, but the lack of tractable genetic systems has limited progress in understanding and interfering with the offending fungal products. In Blastomyces dermatitidis, the agent of blastomycosis, a respiratory and disseminated mycosis of people and animals worldwide, expression of the putative adhesin encoded by the WI-1 gene was investigated as a possible virulence factor. DNA-mediated gene transfer was used to disrupt the WI-1 locus by allelic replacement, resulting in impaired binding and entry of yeasts into macrophages, loss of adherence to lung tissue, and abolishment of virulence in mice; each of these properties was fully restored after reconstitution of WI-1 by means of gene transfer. These findings establish the pivotal role of WI-1 in adherence and virulence of B. dermatitidis yeasts. To our knowledge, they offer the first example of a genetically proven virulence determinant among systemic dimorphic fungi, and underscore the value of reverse genetics for studies of pathogenesis in these organisms. (+info)
Thoracic blastomycosis and empyema.
(3/211)
Blastomycosis is endemic in river valley areas of the southeastern and Midwestern United States. Pulmonary manifestations include chronic cough and pleuritic pain. Radiographic appearance of the infection can mimic bronchogenic lung carcinoma. Pleural effusion is rarely associated with this pulmonary infection, and empyema has not been previously reported. We report a case of pulmonary and pleural Blastomyces dermatitidis infection presenting as empyema thoracis. Diagnosis and treatment were attained with video-assisted thoracoscopic (VATS) pleural and lung biopsy and debridement. (+info)
Disseminated blastomycosis in a rhesus monkey (Macaca mulatta).
(4/211)
An 8-year-old male rhesus monkey (Macaca mulatta) died following a 6-day illness consisting of progressive depression, anorexia, labored abdominal breathing, coughing, and tachypnea. Gross necropsy findings included severe multifocal (miliary) granulomatous pneumonia, granulomatous splenitis, and multifocal cerebral abscesses. Histologic examination revealed 10-15-microm broad-based budding organisms within pyogranulomatous inflammatory lesions in the lung, tracheobronchial lymph node, brain, spleen, and liver. The distribution of extrapulmonary lesions was intermediate between that described for dogs and that described for humans. These findings were consistent with blastomycosis, which is previously unreported in nonhuman primates. (+info)
T-Cell epitopes and human leukocyte antigen restriction elements of an immunodominant antigen of Blastomyces dermatitidis.
(5/211)
Humans infected with the dimorphic fungus Blastomyces dermatitidis develop strong T-lymphocyte responses to WI-1, an immunodominant antigen that has been shown to elicit protective immunity in mice. In the present study, the T-cell epitopes of WI-1 and human leukocyte antigen (HLA) restricting elements that display them were investigated. Peripheral blood mononuclear cells (PBMC) from 37 patients with a confirmed history of blastomycosis were tested for a response to WI-1 in primary proliferation assays; PBMC from 35 (95%) responded. Six patients whose PBMC proliferated strongly in response to WI-1 (defined as a stimulation index greater than 50) were tested further for responses to subcloned, recombinant fragments of the antigen. These patients responded chiefly to sequences within the N terminus and the 25-amino-acid tandem repeat. Cloned CD4(+) T cells from an infected individual were used to delineate more precisely the peptide epitopes in the fragments and HLA restricting elements that present them. A majority of the T-cell clones recognized an epitope spanning amino acids 149 to 172 within the N terminus, displayed by HLA-DR 15. A minority of the clones, which have been shown to perform a cytolytic function in vitro, recognized an epitope in the tandem repeat displayed by HLA-DPw4, an uncommon restricting element. Tandem repeat epitopes required display by the beta chain of DPw4 heterodimers. Thus, human T cells with different functions in vitro also recognize distinct regions of WI-1, raising the possibility that HLA restricting elements that present them could modulate immunity during blastomycosis by selection and display of WI-1 peptides. (+info)
Molecular epidemiology of Blastomyces dermatitidis.
(6/211)
The inhalation of conidia of Blastomyces dermatitidis, a fungus found in soil, causes disease in humans and animals. We studied the genetic diversity of this pathogen by extracting DNA yeasts and analyzing them with a polymerase chain reaction (PCR)-based typing system we developed, which used restriction fragment analysis of amplicons from the regions between the rDNA repeats and allowed us to class isolates into 3 major groups. Strains were further differentiated by use of PCR fingerprinting with 3 different primers. Fifty-nine isolates collected over 35 years from 15 regions (United States, India, Africa, Canada) were analyzed. Genotypic groups A, B, and C contained 17, 23, and 19 isolates, which were divided into 5, 15, and 12 types, respectively. All 16 isolates from North America in group A were from the upper midwestern United States or Canada, whereas 0 of 20 isolates from the southeastern United States were in group A. Studies of the largest collection from 1 locale (Eagle River, WI), revealed that the soil isolates studied were not responsible for the majority of cases in this outbreak, as previously proposed, and that >1 strain was present in the environment and in patients. Overall, these results provide a tool for the epidemiological study of blastomycosis and illuminate the genetic and geographic diversity of this important pathogen. (+info)
Cell wall biogenesis of Blastomyces dermatitidis. Evidence for a novel mechanism of cell surface localization of a virulence-associated adhesin via extracellular release and reassociation with cell wall chitin.
(7/211)
Pathogenic yeast of Blastomyces dermatitidis express a surface protein adhesin, WI-1. Due to the crucial role of WI-1 in adherence and disease pathogenesis, we investigated how the protein localizes to the surface of B. dermatitidis. WI-1 released extracellularly by wild-type yeast coated the surfaces of co-cultured knockout yeast within 3 h of incubation, implying that secreted WI-1 provides a pathway for loading the protein onto the yeast cell wall. In radioligand binding assays, purified WI-1 bound saturably, specifically, and with high affinity (K(d) = 8.3 x 10(-9)) to the cell surface of knockout yeast devoid of WI-1. WI-1 added exogenously, in vitro, to knockout yeast was indistinguishable from native cell surface WI-1 by fluorescence staining and restored adhesivity to the knockout yeast in macrophage binding and phagocytosis assays. Analysis of interactions between WI-1 and elements of the yeast cell wall identified chitin as the anchor point for WI-1. This interaction was shown to hinge on the 24-amino acid tandem repeat sequence of WI-1. Efforts to extract surface WI-1 from the yeast demonstrated that it is fastened to the wall by non-covalent interactions and covalent links between cysteine residues. We conclude that the yeast cell surface adhesin WI-1 localizes to the cell wall, in part, through extracellular release followed by high affinity binding back onto exposed chitin fibrils. These findings point to a novel pathway of cell wall biogenesis in yeast and an unanticipated role for chitin in anchoring and displaying a surface adhesin and virulence determinant. (+info)
Expanding epidemiology of blastomycosis: clinical features and investigation of 2 cases in Colorado.
(8/211)
On the basis of case reports of blastomycosis, Blastomyces dermatitidis is widely accepted to be endemic in the central United States in and around the Ohio and Mississippi River Valleys. Blastomycosis also occurs in parts of Canada and in the southeastern United States. However, there has been no large-scale skin testing, and the environmental range of B. dermatitidis may have been underestimated. We describe 2 immunocompetent patients with blastomycosis acquired while working in the Front Range region of the Rocky Mountains. The patients were coworkers engaged in a prairie dog relocation project. In the course of this work, they had extensive contact with contaminated soil. Significantly above-average rainfall before the exposure may have contributed to favorable conditions for sporulation of the fungus. (+info)