Molecular mechanisms that govern infection and antifungal resistance in Mucorales.

SUMMARYThe World Health Organization has established a fungal priority pathogens list that includes species critical or highly important to human health. Among them is the order Mucorales, a fungal group comprising at least 39 species responsible for the life-threatening infection known as mucormycosis. Despite the continuous rise in cases and the poor prognosis due to innate resistance to most antifungal drugs used in the clinic, Mucorales has received limited attention, partly because of the difficulties in performing genetic manipulations. The COVID-19 pandemic has further escalated cases, with some patients experiencing the COVID-19-associated mucormycosis, highlighting the urgent need to increase knowledge about these fungi. This review addresses significant challenges in treating the disease, including delayed and poor diagnosis, the lack of accurate global incidence estimation, and the limited treatment options. Furthermore, it focuses on the most recent discoveries regarding the mechanisms and genes involved in the development of the disease, antifungal resistance, and the host defense response. Substantial advancements have been made in identifying key fungal genes responsible for invasion and tissue damage, host receptors exploited by the fungus to invade tissues, and mechanisms of antifungal resistance. This knowledge is expected to pave the way for the development of new antifungals to combat mucormycosis. In addition, we anticipate significant progress in characterizing Mucorales biology, particularly the mechanisms involved in pathogenesis and antifungal resistance, with the possibilities offered by CRISPR-Cas9 technology for genetic manipulation of the previously intractable Mucorales species.

COVID-19 Associated Rhino-Orbital-Cerebral Mucormycosis: A Proposed Classification and Treatment Strategies.

OBJECTIVES: Mucormycosis is a rare fungal disease, which was known to affect only immunocompromised hosts, but during the COVID-19 pandemic, a surge in the cases of rhino- orbital-cerebral mucormycosis have been reported; however, the cause is still unknown. As the disease was a rare entity, there was no classification considering the spread and proper management at various stages. METHODS: Extensive literature search with the terms "mucormycosis," "invasive fungal sinusitis," "COVID-19 associated mucormycosis," and "mucormycosis in COVID-19" was conducted on Pubmed, Scopus, and Embase database, taking into consideration case histories, revealing the site of involvement and treatment based on the disease's extent. RESULTS: Relevant articles were analyzed, and it was found that there is no specific classification of the disease entity and no proper surgical and medical management guidelines to date, Conclusion: This review is an attempt to elaborate on the pathophysiology of mucormycosis and its spread and propose a classification that will help determine policies for the control and prevention of complications, morbidity, and mortality.