Molecular mechanisms of mucormycosis—The bitter and the sweet

During the past 2 decades, mucormycosis has become the third most common invasive fungal infection in patients with hematological malignancies and organ transplantations [1]. This life-threatening disease is caused by ubiquitous fungi in the order Mucorales, predominantly by Rhizopus species including R. delemar and R. oryzae. Other common causative organisms include species of Mucor, Lichtheimia (previously Absidia), Apophysomyces, Rhizomucor, and Cunninghamella [1, 2]. The main risk factors for developing mucormycosis are neutropenia due to cancer treatment, hematopoietic and solid organ transplantation, diabetes mellitus, in particular when presenting with ketoacidosis (DKA), and other forms of acidosis. However, immunocompetent subjects can be affected when afflicted with trauma (e.g., soldiers in combat operations and patients with injuries due to natural disasters) [3, 4]. It is likely that mucormycosis will continue to increase in incidence because the number of organ transplantations, cancer patients, and diabetic patients is on the rise. Just in the United States in 2015, the number of transplant patients exceeded 30,000, with an increase of nearly 5% over 2014 (Organ Procurement and Transplantation Network [OPTN]). According to WHO, the number of people affected by diabetes quadrupled in the past 4 decades, reaching >420 million in 2014. Additionally, due to global warming, natural disasters with outbreaks of mucormycosis are likely to occur with higher frequency, similar to what happened with the 2004 Southeast Asia tsunami [5] and the 2011 Joplin tornado [4]. Despite current treatment options, which often include widespread disfiguring surgical intervention and antifungal therapy, mortality rates due to mucormycosis range between 50%–100% [6]. Consequently, novel strategies to prevent and/or treat mucormycosis are needed and can be facilitated by understanding the pathogenesis of the disease.