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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 -
Journal of Fungi (Basel, Switzerland) Dec 2015Pathogens reduce immune recognition of their cell surfaces using a variety of inert structural polysaccharides. For example, capsular polysaccharides play critical roles... (Review)
Review
Pathogens reduce immune recognition of their cell surfaces using a variety of inert structural polysaccharides. For example, capsular polysaccharides play critical roles in microbial survival strategies. Capsules are widely distributed among bacterial species, but relatively rare in eukaryotic microorganisms, where they have evolved considerable complexity in structure and regulation and are exemplified by that of the HIV/AIDS-related fungus . Endemic fungi that affect normal hosts such as and have also evolved protective polysaccharide coverings in the form of immunologically inert α-(1,3)-glucan polysaccharides to protect their more immunogenic β-(1,3)-glucan-containing cell walls. In this review we provide a comparative update on bacterial and fungal capsular structures and immunogenic properties as well as the polysaccharide masking strategies of endemic fungal pathogens.
PubMed: 29376918
DOI: 10.3390/jof1030397 -
Urology Case Reports May 2022Blastomycosis is an endemic infection caused by Blastomyces dermatitidis, found primarily in the southeastern, south-central, and Midwest United States. While the...
Blastomycosis is an endemic infection caused by Blastomyces dermatitidis, found primarily in the southeastern, south-central, and Midwest United States. While the majority of infections typically present with pulmonary manifestations, they rarely present with symptoms isolated to the prostate. In order to better understand the clinical presentation, evaluation, and treatment of blastomycosis of the prostate, we present a 59-year-old male with urinary retention and lower urinary tract symptoms (LUTS).
PubMed: 35145870
DOI: 10.1016/j.eucr.2022.102007 -
MBio Feb 2022Host genetic determinants that underpin variation in susceptibility to systemic fungal infection are poorly understood. Genes responsible for complex traits can be...
Host genetic determinants that underpin variation in susceptibility to systemic fungal infection are poorly understood. Genes responsible for complex traits can be identified by correlating variation in phenotype with allele in founder strains of wild mice with known genetic variation, assembled in genetic reference panels. In this work, we describe wide natural variation in both primary and acquired resistance to experimental pulmonary blastomycosis in eight founder strains, including 129, A/J, BL/6, CAST, NOD, NZO, PWK, and WSB of the Collaborative Cross collection, and the inbred DBA strain. These differences in susceptibility across strains were accompanied by sharp differences in the accumulation and function of immune cells in the lungs. Immune perturbations were mapped by identifying reagents that phenotypically mark immune cell populations in the distinct strains of mice. In particular, we uncovered marked differences between BL/6 and DBA/2 mouse strains in the development of acquired resistance. Our findings highlight the potential value in using genetic reference panels of mice, and particularly the BXD (recombinant inbred strains of mice from a cross of C57BL/6J and DBA/2J mice) collection harboring a cross between resistant BL/6 and susceptible DBA/2 mice, for unveiling genes linked with host resistance to fungal infection. Host genetic variation significantly impacts vulnerability to infectious diseases. While host variation in susceptibility to fungal infection with dimorphic fungi has long been recognized, genes that underpin this variation are poorly understood. We used a collection of seven mouse strains that represent nearly 90% of the genetic variation in mice to identify genetic variability among the strains in resistance to pulmonary infection with the dimorphic fungus Blastomyces dermatitidis. We analyzed differences between the strains in innate resistance by infecting naive mice and in acquired resistance by infecting vaccinated mice. We identified extreme variations in both innate and acquired resistance among the strains. In particular, we found sharp differences between C57BL/6 and DBA/2 strains in the ability to acquire vaccine-induced resistance. We also identified commercial reagents that allowed the phenotyping of immune cells from this strain collection of mice. Because there are additional mice harboring a genetic cross of the C57BL/6 and DBA/2 strains (BXD collection), such mice will permit future investigations to identify the genes that underlie differences in the ability to acquire resistance to infection.
Topics: Animals; Mice; Blastomyces; Immunophenotyping; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred NOD; Mice, Inbred Strains
PubMed: 35089087
DOI: 10.1128/mbio.03400-21 -
Cureus Oct 2022Blastomycosis is caused by Blastomyces dermatitidis, which is endemic in certain areas in North America. It usually causes lung infection, and it can disseminate to...
Blastomycosis is caused by Blastomyces dermatitidis, which is endemic in certain areas in North America. It usually causes lung infection, and it can disseminate to other organs in immunocompromised individuals. Common sites for dissemination include skin, central nervous system (CNS), and bone. Dermatological spread is the commonest site for extrapulmonary spread. The diagnosis can be easily missed due to nonspecific presentation and variable dermatological presentations. Treatment is necessary even if the patient has improvement in symptoms without previous treatment. We present a case of disseminated blastomycosis in a 40-year-old male without known risk factors that went undiagnosed for over a year.
PubMed: 36407244
DOI: 10.7759/cureus.30391 -
Pediatric Radiology May 2023Clinically significant endemic mycoses (fungal infections) in the United States (U.S.) include Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides... (Review)
Review
Clinically significant endemic mycoses (fungal infections) in the United States (U.S.) include Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides immitis/posadasii. While the majority of infections go clinically unnoticed, symptomatic disease can occur in immunocompromised or hospitalized patients, and occasionally in immune-competent individuals. Clinical manifestations vary widely and their diagnosis may require fungal culture, making the rapid diagnosis a challenge. Imaging can be helpful in making a clinical diagnosis prior to laboratory confirmation, as well as assist in characterizing disease extent and severity. In this review, we discuss the three major endemic fungal infections that occur in the U.S., including mycology, epidemiology, clinical presentations, and typical imaging features with an emphasis on the pediatric population.
Topics: Child; Humans; Blastomycosis; Histoplasmosis; Coccidioidomycosis; Mycoses; North America
PubMed: 36922418
DOI: 10.1007/s00247-023-05636-3 -
Clinical Infectious Diseases : An... Oct 2021Blastomycosis has been reported from countries in Africa and the Middle East, but a decades-long debate has persisted regarding whether this is the same disease known in... (Review)
Review
BACKGROUND
Blastomycosis has been reported from countries in Africa and the Middle East, but a decades-long debate has persisted regarding whether this is the same disease known in North America and caused by Blastomyces dermatitidis and Blastomyces gilchristii.
METHODS
We reviewed published cases of human and veterinary blastomycosis from Africa and the Middle East. We abstracted epidemiological and clinical features of cases, including sites of disease, diagnosis, management, outcomes, and, where available, genetic and antigenic typing of case isolates. In addition, we sequenced nucleic acids from 9 clinical isolates from Africa deposited in global collections as B. dermatitidis; for 5, we sequenced the internal transcribed spacer regions, and for the other 4 we sequenced the whole genomes.
RESULTS
We identified 172 unique human patients with blastomycosis, including 159 patients from 25 African countries and 12 patients from 5 Middle Eastern countries, and also identified 7 reports of veterinary blastomycosis. In humans, cutaneous disease predominated (n = 100/137, 73%), followed by pulmonary (n = 73/129, 57%) and osteoarticular involvement (n = 61/128, 48%). Unusual direct microscopy/histopathological presentations included short hyphal fragments in tissues (n = 23/129, 18%). There were 34 genotyped case isolates that comprised 4 species: Blastomyces percursus (n = 22, 65%), from 8 countries throughout all regions; Blastomyces emzantsi (n = 9, 26%), from South Africa; B. dermatitidis (n = 1, 3%), from the Democratic Republic of Congo; and B. gilchristii (n = 2, 6%), from South Africa and Zimbabwe.
CONCLUSIONS
Blastomycosis occurs throughout Africa and the Middle East and is caused predominantly by B. percursus and, at least in South Africa, B. emzantsi, resulting in distinct clinical and pathological patterns of disease.
Topics: Blastomyces; Blastomycosis; Humans; Middle East; South Africa
PubMed: 32766820
DOI: 10.1093/cid/ciaa1100 -
Urology Case Reports Sep 2023A 25 year old male presented with several weeks of fevers and testicular pain. Workup demonstrated scrotal and prostatic abscesses. Fluid from these following surgical...
A 25 year old male presented with several weeks of fevers and testicular pain. Workup demonstrated scrotal and prostatic abscesses. Fluid from these following surgical drainage revealed Blastomyces dermatitidis. He was treated with 12 months of oral anti-fungal therapy and repeat Blastomyces urine antigen was negative at follow up. While disseminated blastomycosis most commonly presents with pulmonary and cutaneous manifestations, genitourinary symptoms are rarely seen, but important to consider.
PubMed: 37455778
DOI: 10.1016/j.eucr.2023.102489 -
Medical Mycology Mar 2010Blastomycosis is a serious and potentially fatal infection caused by the thermally dimorphic fungus Blastomyces dermatitidis. Polymerase chain reaction (PCR) assays...
Blastomycosis is a serious and potentially fatal infection caused by the thermally dimorphic fungus Blastomyces dermatitidis. Polymerase chain reaction (PCR) assays targeting the BAD-1 virulence gene promoter have been developed to aid in the detection of the pathogen in clinical and environmental samples. However, little is known regarding the genetic diversity of B. dermatitidis and how this might affect the performance characteristics of these assays. We explored the genetic relatedness of 106 clinical and environmental isolates of B. dermatitidis using a previously described rDNA PCR restriction fragment length polymorphism (RFLP) assay. In addition, we looked for polymorphisms in the promoter region upstream of BAD-1. RFLP analysis showed that all isolates fell into one of five genotypic groups, designated A through E. Genotypic groups A and B predominated, comprising 50/106 (47.2%) and 51/106 (48.1%) of isolates, respectively. Three of 106 (2.8%) isolates were genotype C. Genotypes D and E represented novel genotypes and were each associated with single clinical isolates. PCR of the BAD-1 promoter revealed significant size differences among amplification products. Fifty-one of 106 isolates (50/50 RFLP genotypic group A and 1/51 genotypic group B) had amplicons of 663-bp, nearly twice the size of the expected product. Sequence analysis of amplification products from 17 representative isolates revealed four haplotypes and showed that the size disparity was due to two large insertions. Because these insertions were present in a high percentage of isolates, the utility of the PCR assays for diagnostic purposes could be affected. However, the novel RFLP genotypes and multiple BAD-1 haplotypes may prove useful as markers in population genetic studies.
Topics: Animals; Base Sequence; Blastomyces; Blastomycosis; DNA, Fungal; Environmental Microbiology; Humans; Molecular Sequence Data; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Promoter Regions, Genetic; Sequence Alignment; Virulence
PubMed: 19626547
DOI: 10.1080/13693780903103952 -
FEMS Immunology and Medical Microbiology Sep 2005Clinical isolates of Coccidioides spp. and Blastomyces dermatitidis can be identified by chemiluminescent DNA probes and PCR assays targeting multicopy genes. In fixed... (Review)
Review
Clinical isolates of Coccidioides spp. and Blastomyces dermatitidis can be identified by chemiluminescent DNA probes and PCR assays targeting multicopy genes. In fixed tissue samples, cells of the two fungi are specified by in situ hybridization and PCR assays targeting 18S rDNA but sequencing of the products is mandatory. Nested PCR assays targeting genes encoding species- or genus-specific proteins like proline rich antigen of Coccidioides spp. and B. dermatitidis adhesin facilitate amplification of specific DNA from fixed tissue samples. The value of DNA amplification from native specimens of suspected cases of coccidioidomycosis or blastomycosis still needs to be determined.
Topics: Animals; Blastomyces; Blastomycosis; Coccidioides; Coccidioidomycosis; DNA Probes; DNA, Fungal; DNA, Ribosomal; Humans; Luminescent Measurements; Polymerase Chain Reaction; RNA, Ribosomal, 18S
PubMed: 16043334
DOI: 10.1016/j.femsim.2005.05.011