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Clinical Microbiology Reviews Apr 2010Blastomycosis is endemic in regions of North America that border the Great Lakes and the St. Lawrence River, as well as in the Mississippi River and Ohio River basins.... (Review)
Review
Blastomycosis is endemic in regions of North America that border the Great Lakes and the St. Lawrence River, as well as in the Mississippi River and Ohio River basins. Men are affected more often than women and children because men are more likely to participate in activities that put them at risk for exposure to Blastomyces dermatitidis. Human infection occurs when soil containing microfoci of mycelia is disturbed and airborne conidia are inhaled. If natural defenses in the alveoli fail to contain the infection, lymphohematogenous dissemination ensues. Normal host responses generate a characteristic pyogranulomatous reaction. The most common sites of clinical disease are the lung and skin; osseous, genitourinary, and central nervous system manifestations follow in decreasing order of frequency. Blastomycosis is one of the great mimickers in medicine; verrucous cutaneous blastomycosis resembles malignancy, and mass-like lung opacities due to B. dermatitidis often are confused with cancer. Blastomycosis may be clinically indistinguishable from tuberculosis. Diagnosis is based on culture and direct visualization of round, multinucleated yeast forms that produce daughter cells from a single broad-based bud. Although a long course of amphotericin B is usually curative, itraconazole is also highly effective and is the mainstay of therapy for most patients with blastomycosis.
Topics: Blastomyces; Blastomycosis; Female; Humans; Male
PubMed: 20375357
DOI: 10.1128/CMR.00056-09 -
International Journal of Infectious... Oct 2012
Topics: Aged; Antifungal Agents; Blastomyces; Blastomycosis; Dermatomycoses; Fatal Outcome; Female; Humans
PubMed: 22704726
DOI: 10.1016/j.ijid.2012.04.003 -
Emerging Infectious Diseases May 2020Blastomycosis is a systemic disease caused by Blastomyces spp. fungi. To determine its epidemiology in blastomycosis-endemic Minnesota, USA, we evaluated all cases...
Blastomycosis is a systemic disease caused by Blastomyces spp. fungi. To determine its epidemiology in blastomycosis-endemic Minnesota, USA, we evaluated all cases reported to public health officials during 1999-2018. We focused on time to diagnosis, exposure activities, and exposure location. A total of 671 cases and a median of 34 cases/year were reported. Median time to diagnosis was 31 days; 61% of patients were not tested for blastomycosis until they were hospitalized. The case-fatality rate was 10%, and patients who died were 5.3 times more likely to have a concurrent medical condition. Outdoor activities and soil exposure were reported by many patients, but no specific activity or exposure was common to most. Almost one third of patients were probably exposed in geographic areas other than their home county. Providers should consider alternative etiologies for patients with pneumonia not responding to antibacterial treatment, and public health officials should increase awareness in blastomycosis-endemic areas.
Topics: Anti-Bacterial Agents; Antifungal Agents; Blastomyces; Blastomycosis; Humans; Minnesota; Public Health
PubMed: 32310071
DOI: 10.3201/eid2605.191074 -
Journal of Clinical Microbiology Sep 2011Blastomyces dermatitidis and Histoplasma capsulatum are dimorphic fungi that often cause self-limited respiratory infections. However, they may also cause severe...
Blastomyces dermatitidis and Histoplasma capsulatum are dimorphic fungi that often cause self-limited respiratory infections. However, they may also cause severe disseminated disease, depending on the level of the exposure to the organism and the host immune status. In addition, patients with infections caused by these fungi may have very similar clinical presentations. Although microbiologic culture is a standard method for detecting these pathogens, their recovery may require days to weeks, and the manipulation of cultures presents a significant safety hazard to laboratory personnel. Therefore, the goal of this study was to design a rapid, real-time PCR assay to detect and differentiate B. dermatitidis and H. capsulatum from culture isolates and directly from clinical specimens. Primers and fluorescence resonance energy transfer hybridization probes were designed to target the histidine kinase and glyceraldehyde-3-phosphate dehydrogenase genes of B. dermatitidis and H. capsulatum, respectively. The analytical sensitivity of the assay was determined to be 100 copies/μl for both fungi. From culture isolates, the assay demonstrated 100% specificity and 100% sensitivity for B. dermatitidis and 100% specificity and 94% sensitivity for H. capsulatum. Detection directly from 797 clinical specimens demonstrated specificities and sensitivities of 99% and 86% for B. dermatitidis and 100% and 73% for H. capsulatum compared with the results for culture. This real-time PCR assay provides a rapid method for the detection of B. dermatitidis and H. capsulatum from culture isolates and directly from clinical specimens.
Topics: Blastomyces; Blastomycosis; DNA Primers; Fluorescence Resonance Energy Transfer; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); Histidine Kinase; Histoplasma; Histoplasmosis; Humans; Molecular Diagnostic Techniques; Oligonucleotide Probes; Protein Kinases; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 21752970
DOI: 10.1128/JCM.00673-11 -
Archives of Biochemistry and Biophysics Dec 2020Histoplasma capsulatum is an ascomyceteous fungus and a human lung pathogen, which is present in river valleys of the Americas and other continents. H. capsulatum and...
Histoplasma capsulatum is an ascomyceteous fungus and a human lung pathogen, which is present in river valleys of the Americas and other continents. H. capsulatum and two related human pathogens, Blasmomyces dermatitidis and Paracoccidioides brasiliensis, belongs to the Ajellomycetaceae family. The genomes of all three species code for three homologous and tentative enzymes of the linoleate diol synthase (LDS) family of fusion enzymes with dioxygenase (DOX) and cytochrome P450 domains. One group aligned closely with 8R-DOX-5,8-LDS of Aspergilli, which oxidizes linoleic acid to 5S,8R-dihydroxylinoleic acid; this group was not further investigated. The second group aligned with 10R-DOX-epoxy alcohol synthase (EAS) of plant pathogens. Expression of this enzyme from B. dermatitidis revealed only 10R-DOX activities, i.e., oxidation of linoleic acid to 10R-hydroperoxy-8E,12Z-octadecadienoic acid. The third group aligned in a separate entity. Expression of these enzymes of H. capsulatum and B. dermatitidis revealed no DOX activities, but both enzymes transformed 13S-hydroperoxy-9Z,11E-octadecadienoic acid efficiently to 12(13S)epoxy-11-hydroperoxy-9Z-octadecenoic acid. Other 13-hydroperoxides of linoleic and α-linolenic acids were transformed with less efficiency and the 9-hydroperoxides of linoleic acid were not transformed. In conclusion, a novel EAS has been found in H. capsulatum and B. dermititidis with 13S-hydroperoxy-9Z,11E-octadecadienoic acid as the likely physiological substrate.
Topics: Amino Acid Sequence; Blastomyces; Catalysis; Dioxygenases; Fatty Acids, Unsaturated; Fungal Proteins; Histoplasma; Intramolecular Oxidoreductases; Oxygenases; Phylogeny; Recombinant Proteins
PubMed: 33189651
DOI: 10.1016/j.abb.2020.108669 -
Emerging Infectious Diseases Nov 2021This retrospective multicenter cohort study assessed temporal changes in the severity and mortality rate of blastomycosis in Quebec, Canada, and identified risk factors...
This retrospective multicenter cohort study assessed temporal changes in the severity and mortality rate of blastomycosis in Quebec, Canada, and identified risk factors for death in patients with blastomycosis in 1988-2016. The primary outcome was 90-day all-cause deaths. Among 185 patients, 122 (66%) needed hospitalization and 30 (16%) died. We noted increases in the proportion of severe cases, in age at diagnosis and in the proportion of diabetic and immunocompromised patients over time. Independent risk factors for death were age (adjusted odds ratio [aOR] 1.04, 95% CI 1.00-1.07), immunosuppression (aOR 4.2, 95% CI 1.5-11.6), and involvement of >2 lung lobes (aOR 5.3, 95% CI 1.9-14.3). There was no association between the Blastomyces genotype group and all-cause mortality. The proportion of severe cases of blastomycosis has increased in Quebec over the past 30 years, partially explained by the higher number of immunosuppressed patients.
Topics: Blastomyces; Blastomycosis; Cohort Studies; Humans; Quebec; Retrospective Studies; Severity of Illness Index
PubMed: 34670643
DOI: 10.3201/eid2711.210552 -
Current Opinion in Microbiology Aug 2007The signature feature of systemic dimorphic fungi - a family of six primary fungal pathogens of humans - is a temperature-induced phase transition. These fungi grow as a... (Review)
Review
The signature feature of systemic dimorphic fungi - a family of six primary fungal pathogens of humans - is a temperature-induced phase transition. These fungi grow as a mold in soil at ambient temperature and convert to yeast after infectious spores are inhaled into the lungs of a mammalian host. Seminal work 20 years ago established that a temperature-induced phase transition from mold to yeast is required for virulence. Several yeast-phase specific genes, identified one-by-one and studied by reverse genetics, have revealed mechanisms by which the phase transition promotes disease pathogenesis. Transcriptional profiling of microarrays built with genomic elements of Histoplasma capsulatum and ESTs of Paracoccidioides brasiliensis that represent partial genomes has identified 500 genes and 328 genes, respectively, that are differentially expressed upon the phase transition. The genomes of most of the dimorphic fungi are now in varying stages of being sequenced. The creation of additional microarrays and the application of new reverse genetic tools promise fresh insight into genes and mechanisms that regulate pathogenesis and morphogenesis. The use of insertional mutagenesis by Agrobacterium has uncovered a hybrid histidine kinase that regulates dimorphism and pathogenicity in Blastomyces dermatitidis and H. capsulatum. Two-component signaling appears to be a common strategy for model and pathogenic fungi to sense and respond to environmental stresses.
Topics: Animals; Fungi; Gene Expression Regulation, Fungal; Humans; Mycoses; Virulence
PubMed: 17719267
DOI: 10.1016/j.mib.2007.04.002 -
Journal of Clinical Microbiology Feb 2020We reevaluated 20 cases of blastomycosis diagnosed in South Africa between 1967 and 2014, with considered to be the etiological agent, in light of newly described...
We reevaluated 20 cases of blastomycosis diagnosed in South Africa between 1967 and 2014, with considered to be the etiological agent, in light of newly described species and the use of more advanced technologies. In addition to histopathological and/or culture-based methods, all 20 isolates were phenotypically and genotypically characterized, including multilocus typing of five genes and whole-genome sequencing. Antifungal susceptibility testing was performed as outlined by Clinical and Laboratory Standards Institute documents M27-A3 and M38-A2. We merged laboratory and corresponding clinical case data, where available. Morphological characteristics and phylogenetic analyses of five-gene and whole-genome sequences revealed two groups, both of which were closely related to but distinct from , , and The first group ( = 12) corresponded to the recently described species , and the other ( = 8) is described here as sp. nov. Both species exhibited incomplete conversion to the yeast phase at 37°C and were heterothallic for mating types. All eight isolates belonged to the α mating type. Whole-genome sequencing confirmed distinct species identities as well as the absence of a full orthologue of the gene. Extrapulmonary (skin or bone) disease, probably resulting from hematogenous spread from a primary lung infection, was more common than pulmonary disease alone. Voriconazole, posaconazole, itraconazole, amphotericin B, and micafungin had the most potent activity. Over the 5 decades, South African cases of blastomycosis were caused by species that are distinct from Increasing clinical awareness and access to simple rapid diagnostics may improve the diagnosis of blastomycosis in resource-limited countries.
Topics: Blastomyces; Blastomycosis; Humans; Male; Phylogeny; South Africa
PubMed: 31896663
DOI: 10.1128/JCM.01661-19 -
Frontiers in Microbiology 2020Invasive fungal infections (IFI) cause devastating morbidity and mortality, with the number of IFIs more than tripling since 1979. Our laboratories were the first to...
Invasive fungal infections (IFI) cause devastating morbidity and mortality, with the number of IFIs more than tripling since 1979. Our laboratories were the first to demonstrate that radiolabeled microorganism-specific monoclonal antibodies are highly effective for treatment of experimental fungal, bacterial and viral infections. Later we proposed to utilize surface expressed pan-antigens shared by major IFI-causing pathogens such as beta-glucans as RIT targets. Here we evaluated RIT targeting beta-glucan in which causes serious infections in immunocompromised and immunocompetent individuals and in companion dogs. cells were treated with the 400-2 antibody to (1→3)-β-glucans radiolabeled with the beta-emitter 177Lutetium (Lu) and alpha-emitter 213Bismuth (Bi) and the efficacy of cell kill was determined by colony forming units (CFUs). To determine the antigen-specific localization of the 400-2 antibody , C57BL6 mice were infected intratracheally with 2 × 10 cells and given In-400-2 antibody 24 h later. To evaluate the killing of cells with RIT, intratracheally infected mice were treated with 150 μCi Bi-400-2 and their lungs analyzed for CFUs 96 h post-infection. Bi-400-2 proved to be more effective in killing cells than Lu-400-2. Three times more In-400-2 accumulated in the lungs of infected mice, than in the non-infected ones. Bi-400-2 lowered the fungal burden in the lungs of infected mice more than 2 logs in comparison with non-treated infected controls. In conclusion, our results demonstrate the ability of an anti-(1-3)-beta-D-glucan antibody armed with an alpha-emitter Bi to selectively kill cells and . These first results of the effectiveness of RIT targeting pan-antigens on fungal pathogens warrant further investigation.
PubMed: 32117166
DOI: 10.3389/fmicb.2020.00147 -
Infection and Immunity Jun 2010Blastomyces dermatitidis is a thermally induced dimorphic fungus capable of causing lung and systemic infections in immunocompetent animal hosts. With the publication of...
Blastomyces dermatitidis is a thermally induced dimorphic fungus capable of causing lung and systemic infections in immunocompetent animal hosts. With the publication of genomic sequences from three different strains of B. dermatitidis and the development of RNA interference as a gene-silencing tool, it has become possible to easily ascertain the virulence and morphological effects of knocking down the expression of candidate genes of interest. BYS1 (Blastomyces yeast-phase-specific 1), first identified by Burg and Smith, is expressed at high levels in yeast cells and is undetectable in mold. The deduced protein sequence of BYS1 has a putative signal sequence at its N terminus, opening the possibility that the BYS1-encoded protein is associated with the yeast cell wall. Herein, strains of B. dermatitidis with silenced expression of BYS1 were engineered and tested for morphology and virulence. The silenced strains produced rough-surfaced cultures on agar medium and demonstrated a propensity to form pseudohyphal cells on prolonged culture in vitro and in vivo, as measured in the mouse lung. Tests using a mouse model of blastomycosis with either yeast or spore inocula showed that the bys1-silenced strains were as virulent as control strains. Thus, although silencing of BYS1 alters morphology at 37 degrees C, it does not appear to impair the pathogenicity of B. dermatitidis.
Topics: Animals; Blastomyces; Colony Count, Microbial; Fungal Proteins; Gene Silencing; Genes, Fungal; Hyphae; Lung; Mice; Mice, Inbred C57BL; Virulence
PubMed: 20368350
DOI: 10.1128/IAI.01328-09