New Strategies to Combat Human Fungal Infections

Dear Colleagues,

Over the last decades, several studies have reported a significant increase in the number of fungal infections worldwide, which result in considerable morbidity and mortality, representing substantial rising costs for the health system. The armamentarium to combat fungal infections is extremely limited considering the few available antifungal drugs and their mechanisms of action, presenting considerable toxicity and several side effects to the host. The seriousness of this situation can be better alleged to fungal infections due to their eukaryote cell architecture and conserved gene sequences closely related to metazoans, including humans, which reflect similarities at both biochemical and immunological levels. Making this scenario worse, antifungal resistance is emerging at a threatening rate and no vaccine is available against fungal infections. Corroborating these statements, the extensive use, misuse and overuse of antimicrobial drugs in treating infectious diseases have led to the emergence of resistance in a wide range of pathogens, including fungi, in a global perspective. Antimicrobial resistance is recognized by the World Health Organization (WHO) as the greatest hazard in the treatment of infectious diseases, which caught the attention of global surveillance authorities and public media to solve this extremely delicate problem.

In recent years, we have seen great improvements in medical practices, which have provided an increase in the survival of hospitalized patients suffering from fungi-related infectious diseases. However, this has also caused an increase in the number of opportunistic, nosocomial and fungal infections. Indeed, many current medical practices are based on procedures that lead to immunosuppression of the patient, such as chemotherapy to treat cancer and organ transplantation. In view of this alarming circumstance, a number of new strategies to combat fungal infections are urgently required. Importantly, novel targets in the fungal cell must be discovered. Furthermore, new bioactive compounds must be synthesized and/or found from different sources. In this context, potential lines of research have been raised: the search for original drugs, the search for potential compounds in public databases and the application of drugs already approved for clinical use for a particular purpose against novel targets (or pathogens). Of particular relevance, novel drugs must be capable of blocking crucial biological events in the fungal cell, leading to growth arrest, inhibition of virulence factors and, most importantly, death. Furthermore, recent advances in combating fungal resistance have focused on the effective combination of two or more antifungals during a treatment regimen or a combination of a classical antifungal agent and a non-antibiotic adjuvant (i.e., a compound that is not fungicidal if administered alone, but is able to increase the activity of the antifungal agent by blocking the target responsible for the mechanism of resistance). In the first approach, antimicrobial combination therapy can be divided into three major categories: (i) inhibition of targets in different pathways; (ii) inhibition of different targets in the same pathway; and (iii) inhibition of the same target in different ways. Therefore, the demand for novel effective antifungal drugs as well as new strategies to combat fungal infections is high and urgently needed.

The Guest Editors invite the international scientific mycological community to contribute works on the abovementioned fields, highlighting the relevant developments of novel antifungal compounds, their mechanisms of action, as well as novel strategies to combat human fungal infections. Both research and review papers in these fields are welcome.

Prof. Dr. André Luis Souza Dos Santos
Prof. Dr. Marta Helena Branquinha
Guest Editors

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