The Four Critical Priority Fungi According to the World Health Organization and the Hope for New Therapies: A Focus on Cell Wall Antifungal Targets

In 2022, the World Health Organization (WHO) released a list of four fungi identified as the most medically important global pathogens, resulting in Cryptococcus neoformans, Candidozyma auris (formerly Candida auris), Aspergillus fumigatus and Candida albicans being classified as the critical priority fungi. The purpose of this list is to encourage the prioritization of fungal research and public policies to strengthen its control and combat fungal diseases. Among the criteria used in the analysis by the WHO to determine these critical threat pathogens were numbers of deaths; annual incidence; current global distribution; trends in the last 10 years; hospitalization; complications and sequelae; preventability; access to diagnostic tests; evidence-based treatments; and antifungal resistance. Difficulties in treatment, including due to antifungal resistance, are a major factor in the morbidity and mortality of these fungi. The fungal cell wall plays a fundamental role in maintaining cellular architecture and contributing to fungal survival. Thus, new approaches targeting the cell wall have been and are being developed. This review article aims to bring together studies from the last ten years focusing on the development of new treatment alternatives targeting the cell walls of the four critical priority fungi and discussing their potential for combating these deadly fungi of worldwide clinical importance.