The current therapy for invasive fungal infections like mucormycosis has limited use due to drug toxicity, antifungal resistance, reduced susceptibility, etc, making it necessary to develop new antifungal therapeutics. As a leading service provider in the field of biological research and drug discovery, Creative Biolabs is fully competent and dedicated to providing antifungal drug discovery services. Our profound expertise in this field and years of experience in contract research result in a sustainable advantage for our customers.
Introduction to Mucormycosis
Mucormycosis is a rare but aggressive opportunistic fungal infection that affects mainly immunocompromised subjects (especially those with hematologic malignancies) and those with diabetes mellitus, iron overload, and under treatment with glucocorticoids. The disease spectrum ranges from the involvement of skin, sinuses, lung, and brain to disseminated and mostly fatal infections. Mucormycosis is caused by the ubiquitous filamentous fungi of the order Mucorales and class Zygomycetes.
Pathogenesis of Mucormycosis
The pathogenesis of mucormycosis can be attributed to different factors, including both host factors and virulence factors of Mucorales. Firstly, Mucorales spores must escape killing by resident mononuclear and polymorphonuclear phagocytes to germinate into hyphae, the angioinvasive form of the infection, which eventually disseminate to other organs. Hence, the most common underlying predisposing conditions for mucormycosis are diseases associated with impaired or deficient phagocyte function. Secondly, a key predisposing factor for developing mucormycosis is iron overload. Iron is essential for Mucorales, either enhancing their growth and hyphal development or increasing their pathogenicity. Thirdly, the Mucorales spores are capable of causing rapid onset of tissue infarctions and necrosis and subsequent thrombosis by invading vascular bed. Specific adhesion to endothelial cells and internalization of the fungus by the endothelial cells are important for the pathogenic strategy of Mucorales. Moreover, virulence factors such as enzyme production and toxin production can be implicated.
Fig.1 Pathogenesis of pulmonary mucormycosis. (Lewis, 2013)
The most common types of Mucorales that cause mucormycosis are:
Treatment of Mucormycosis
Treatment of mucormycosis combines surgical intervention and antifungal therapy. The infected tissue often cut away before antifungal therapy is administered. The susceptibility of Mucorales to antifungal drugs varied depending on the genus and species. For better effect, antifungal combination therapy has been successfully used. For instance, combination therapy has been used as aggressive antifungal treatments following surgical resection of the damaged tissue.
Antifungal Drug Development for Mucormycosis
Creative Biolabs offers a full range of antifungal drug discovery services including target identification and validation, hit identification, hit to lead, lead optimization as well as IND-enabling. We have experience in a number of potential disease targets, including cell wall targets, cell membrane targets, biosynthetic pathway, virulence factors, etc. Besides, we provide top-of-the-line services that are characterized by:
Creative Biolabs brings the highest level of technical expertise and judgment to our work. By working with us, you and your team will be able to bring your valuable medicinal chemistry leads into the pipeline with the highest quality and efficiency. For more information about our services please do not hesitate to contact us.
Reference
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