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Virulence Dec 2019This review article focuses on the mechanisms underlying temperature adaptation and virulence of the etiologic agents of blastomycosis, , , and . In response to... (Review)
Review
This review article focuses on the mechanisms underlying temperature adaptation and virulence of the etiologic agents of blastomycosis, , , and . In response to temperature, undergoes a reversible morphologic switch between hyphae and yeast known as the phase transition. The conversion to yeast for and related thermally dimorphic fungi is essential for virulence. In the yeast phase, upregulates the essential virulence factor, BAD1, which promotes attachment to host cells, impairs activation of immune cells, and blunts cytokine release. yeast also secrete dipeptidyl-peptidase IVA (DPPIVA), a serine protease that blunts the action of cytokines released from host immune cells. transcriptional profiling of yeast has uncovered genes such as and involved in zinc scavenging that contribute to virulence during murine pulmonary infection. The discovery and characterization of genes important for virulence has led to advances at the bedside regarding novel diagnostics, vaccine development, and new targets for drug discovery.
Topics: Adaptation, Physiological; Animals; Blastomyces; Blastomycosis; Fungal Proteins; Humans; Hyphae; Mice; Temperature; Transcriptional Activation; Virulence; Virulence Factors
PubMed: 29532714
DOI: 10.1080/21505594.2018.1449506 -
Infection and Immunity Jun 2011The ability of pathogens to evade host antimicrobial mechanisms is crucial to their virulence. The dimorphic fungal pathogen Blastomyces dermatitidis can infect...
The ability of pathogens to evade host antimicrobial mechanisms is crucial to their virulence. The dimorphic fungal pathogen Blastomyces dermatitidis can infect immunocompetent patients, producing a primary pulmonary infection that can later disseminate to other organs. B. dermatitidis possesses a remarkable ability to resist killing by alveolar macrophages. To date, no mechanism to explain this resistance has been described. Here, we focus on macrophage production of the toxic molecule nitric oxide as a potential target of subversion by B. dermatitidis yeast cells. We report that B. dermatitidis yeast cells reduce nitric oxide levels in the supernatants of activated alveolar macrophages. This reduction is not due to detoxification of nitric oxide, but rather to suppression of macrophage nitric oxide production. We show that B. dermatitidis yeast cells do not block upregulation of macrophage inducible nitric oxide synthase (iNOS) expression or limit iNOS access to its arginine substrate. Instead, B. dermatitidis yeast cells appear to inhibit iNOS enzymatic activity. Further investigation into the genetic basis of this potential virulence mechanism could lead to the identification of novel antifungal drug targets.
Topics: Animals; Blastomyces; Blastomycosis; Blotting, Western; Cell Line; Host-Pathogen Interactions; Macrophages, Alveolar; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 21444664
DOI: 10.1128/IAI.01249-10 -
Science (New York, N.Y.) Apr 1961Through the intravenous inoculation of soil suspensions in the tail vein of mice, Blastomyces dermatitidis was recovered from a Lexington, Kentucky, soil sample. The...
Through the intravenous inoculation of soil suspensions in the tail vein of mice, Blastomyces dermatitidis was recovered from a Lexington, Kentucky, soil sample. The positive specimen was collected in a tobacco-stripping barn. The shed had sheltered a dog that died of blastomycosis 2 years before the sample was collected.
Topics: Animals; Blastomyces; Blastomycosis; Dogs; Kentucky; Mice; Soil; Soil Microbiology
PubMed: 13721936
DOI: 10.1126/science.133.3459.1126 -
Diagnostic Microbiology and Infectious... Feb 2011Blastomycosis is a serious and potentially fatal infection, and diagnosis can be difficult at times. We evaluated the diagnostic utility of a commercially available...
Blastomycosis is a serious and potentially fatal infection, and diagnosis can be difficult at times. We evaluated the diagnostic utility of a commercially available assay for detection of Blastomyces dermatitidis antigen, recently modified to permit quantitation, in subjects with newly diagnosed blastomycosis. Twenty-three of 27 (85.1%) subjects had detectable B. dermatitidis antigenuria. In 2 of these 23, positive results were obtained after concentration of the urine specimen. Nine of 11 (81.8%) subjects had detectable B. dermatitidis antigen in serum, including 3 subjects with negative results before treatment of serum with ethylenediaminetetraacetic acid (EDTA) and positive results after EDTA treatment. B. dermatitidis antigen was not detected in specimens from 50 control subjects but was detected in 15 patients with histoplasmosis. B. dermatitidis antigen was detected in most of the patients with blastomycosis and can be a useful tool for timely diagnosis.
Topics: Antigens, Fungal; Blastomyces; Blastomycosis; Cross Reactions; Histoplasmosis; Humans; Sensitivity and Specificity
PubMed: 21251563
DOI: 10.1016/j.diagmicrobio.2010.09.015 -
Saudi Journal of Kidney Diseases and... Sep 2014Fungal pathogens can be the source of serious and sometimes fatal infections following organ transplantation. To the best of our knowledge, we present the first case of...
Fungal pathogens can be the source of serious and sometimes fatal infections following organ transplantation. To the best of our knowledge, we present the first case of cutaneous blastomycosis in a renal allograft recipient in India, a country outside the known endemic regions. This case, with the very rare and unexpected diagnosis of blastomycosis, not only reflects the tremendous diversity of infections in transplant recipients but also emphasizes the utility of serological methods even in the immunosuppressed host.
Topics: Adult; Antifungal Agents; Biopsy; Blastomyces; Blastomycosis; Humans; Immunocompromised Host; Immunosuppressive Agents; India; Kidney Transplantation; Male; Opportunistic Infections; Skin; Treatment Outcome
PubMed: 25193904
DOI: 10.4103/1319-2442.139934 -
Clinical Infectious Diseases : An... Feb 2000The 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...
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.
Topics: Africa; Base Sequence; Blastomyces; Blastomycosis; Canada; Colony Count, Microbial; DNA, Fungal; Genotype; Humans; Incidence; India; Molecular Epidemiology; Molecular Sequence Data; Polymerase Chain Reaction; Sensitivity and Specificity; Species Specificity; United States
PubMed: 10671337
DOI: 10.1086/313649 -
Mycopathologia Sep 2005A competitive binding inhibition enzyme linked immunosorbent assay (ELISA) was used to detect Blastomyces dermatitidis antigens in urine specimens from dogs with...
A competitive binding inhibition enzyme linked immunosorbent assay (ELISA) was used to detect Blastomyces dermatitidis antigens in urine specimens from dogs with blastomycosis. Sera from rabbits immunized with B. dermatitidis killed whole yeast cells were used as the primary antibody in the competitive ELISA. This initial study was performed to determine if B. dermatitidis antigen detection was possible and to test the efficacy of the rabbit sera as a primary antibody. An indirect ELISA was also performed to compare antigen detection in urine to antibody detection in the sera of the infected dogs. The results indicate 100% (36/36 specimens) detection of both antigen and antibody. Cross reactivity with Histoplasma capsulatum, as well as non-specific binding with the normal urine specimens, was observed with the competitive binding inhibition ELISA.
Topics: Animals; Antibodies, Fungal; Antigens, Fungal; Binding, Competitive; Blastomyces; Blastomycosis; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Female; Rabbits
PubMed: 16170609
DOI: 10.1007/s11046-005-3153-9 -
Archives of Pathology & Laboratory... May 2001Yeast forms of Blastomyces dermatitidis typically range from 8 to 20 microm in largest diameter. We report a rare case of primary pulmonary blastomycosis with an unusual...
Yeast forms of Blastomyces dermatitidis typically range from 8 to 20 microm in largest diameter. We report a rare case of primary pulmonary blastomycosis with an unusual morphology, in which we found significant numbers of large yeast forms ranging from 30 to 35 microm in diameter. To our knowledge, this is only the second reported case of giant forms of B dermatitidis. We also review the literature and discuss the possible association of this unusual morphology with immunosuppression in general and glucocorticoid use in particular.
Topics: Aged; Blastomyces; Blastomycosis; Glucocorticoids; Humans; Immunocompromised Host; Lung Diseases, Fungal; Lung Diseases, Obstructive; Male
PubMed: 11300940
DOI: 10.5858/2001-125-0663-BDWLYF -
Science (New York, N.Y.) Apr 1967Growth of five combinations of strains of Blastomyces dermatitidis in paired cultures on yeast-extract agar, plus bone meal, yielded the perfect stage for the first...
Growth of five combinations of strains of Blastomyces dermatitidis in paired cultures on yeast-extract agar, plus bone meal, yielded the perfect stage for the first time. These cleistothecia, apparently of a new genus, produced eight spored asci. Monoascospore cultures developed hyphae and conidia typical of B. dermatitidis. Mice were successfully infected with inocula from a monoascospore culture.
Topics: Agar; Blastomyces; Culture Media; Yeasts
PubMed: 6021679
DOI: 10.1126/science.156.3774.528 -
Medical Mycology Jan 2013Blastomyces dermatitidis, the etiologic agent of blastomycosis, belongs to a group of thermally dimorphic fungi that change between mold (22°C) and yeast (37°C) in...
Blastomyces dermatitidis, the etiologic agent of blastomycosis, belongs to a group of thermally dimorphic fungi that change between mold (22°C) and yeast (37°C) in response to temperature. The contribution of structural proteins such as septins to this phase transition in these fungi remains poorly understood. Septins are GTPases that serve as a scaffold for proteins involved with cytokinesis, cell polarity, and cell morphology. In this study, we use a GFP sentinel RNA interference system to investigate the impact of CDC3, CDC10, CDC12, and ASPE on the morphology and phase transition of B. dermatitidis. Targeting CDC3, CDC10, and CDC12 by RNA interference resulted in yeast with aberrant morphology at 37°C with defects in cytokinesis. Downshifting the temperature to 22°C promoted the conversion to the mold phase, but did not abrogate the morphologic defects. CDC3, CDC10, and CDC12 knockdown strains grew as mold with curved, thickened hyphae. Knocking down ASPE transcript did not alter morphology of yeast at 37°C or mold at 22°C. Following an increase in temperature from 22°C to 37°C, all septin knockdown strains were able to revert to yeast. In conclusion, CDC3, CDC10, and CDC12 septin- encoding genes are required for proper morphology of yeast and hyphae, but are dispensable for the phase transition.
Topics: Blastomyces; Fungal Proteins; Gene Knockdown Techniques; Green Fluorescent Proteins; Hyphae; RNA Interference; Real-Time Polymerase Chain Reaction; Septins; Temperature; Yeasts
PubMed: 22783804
DOI: 10.3109/13693786.2012.699685