Blastomycosis caused by Blastomyces dermatitidis is one of 3 major dimorphic endemic mycoses that occur primarily in North America. Infection with Blastomyces dermatitidis leads to a broad range of clinical manifestations ranging from asymptomatic infection to fulminant sepsis with acute respiratory distress syndrome and death. Currently, scientists at Creative Biolabs are committed to assisting you in the antifungal drug discovery project for the better understanding of the pathogenesis, diagnosis, and treatment of this fungus.
Introduction of Blastomyces Dermatitidis
Blastomyces dermatitidis (B. dermatitidis), a thermally dimorphic fungus, is the causal agent of blastomycosis. This mycosis is an invasive and commonly serious fungal infection existed occasionally in humans and other animals in regions where the fungus is endemic. B. dermatitidis is found as mold at room temperature in the laboratory and in the environment, while it exists as yeast at 37°C in the laboratory and in human tissues. This causal organism lives in soil and wet, decaying wood, which is often in the area close to a waterway such as a river, lake, or stream. Also, it may exist indoor, such as accumulated debris in damp sheds or shacks.
Fig.1 B. dermatitidis mold and yeast. (A) Hyphae with conidia at 22°C. (B) Broad-based budding yeast at 37°C. Scale bar is 10 μm. (Smith, 2015)
Pathogenesis of Blastomyces Dermatitidis
The pulmonary infection, called the blastomycosis, is caused by the inhalation of the spores of B. dermatitidis into the lungs, and these conidia will convert to the yeast phase once in the lungs at body temperature. With thick walls, these yeast phases of B. dermatitidis are resistant to phagocytosis and express glycoprotein, BAD-1, which is an epitope factor as well as virulence. In the majority of patients, a self-limited infection develops. And in a smaller group of patients, a chronic infection limited to the lungs, or disseminated infection involving extrapulmonary sites occurs. Blastomycosis might also occur percutaneous inoculation or take place in the laboratory after accidental inhalation. Natural resistance in the lung is mediated by monocytes, neutrophils, and alveolar macrophages that can phagocytize and kill the conidia.
Antifungal Drugs against Blastomyces Dermatitidis
The cure rates of blastomycosis are high, and the treatment over a period of months is commonly well tolerated. Amphotericin B is considered more toxic, and it is usually applicable to immunocompromised patients who are seriously ill and those with CNS (central nervous system) disease. Patients who are not able to tolerate the deoxycholate formulation of Amphotericin B could be administrated with lipid formulations.
Antifungal Drug Discovery Services at Creative Biolabs
As a world leading CRO service provider, the antifungal drug discovery services team at Creative Biolabs provides the highest quality, full-service contract research to assist you in preclinical antifungal drug development. Moreover, to meet the novel drug discovery goals, we provide a comprehensive service package, ranging from target identification and validation, hit identification, hit to lead, and lead optimization, to IND enabling.
What’s more, Creative Biolabs has been recognized as an expert in fungal disease biology and pathogenesis. If you are interested in our antifungal drug discovery services, please contact us for more details or a detailed quote.
Reference
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