Fungal diseases: A real threat to public health Human fungal diseases differ fundamentally from other infections in diverse ways. As eukaryotic pathogens, fungi share many similarities with their host cells, which impairs the development of antifungal compounds. Fungal tropism is highly variable, as pathogens infect a wide range of cell types. A single fungal pathogen can infect multiple tissues in the same patient (depending on the host's immunological status) and can undergo morphogenic shifts during infection. Fungi are still underappreciated as major pathogens by both the public and public health officials. Diseases caused by protozoa, bacteria, and viruses have been recognized as important public health issues for centuries. For instance, syphilis, influenza, and Chagas disease have been documented for over 100 years [1], while invasive mycoses were only widely acknowledged as medically important pathogens in the 1980s [2]. Viral diseases of major population impact (such as smallpox, influenza and-more recentlydengue, Zika, Chikungunya, and coronavirus) have affected millions of people with significant effects on human health in developed, developing, and less developed nations [3,4]. These conditions have boosted the generation of knowledge, which has led to the eradication of smallpox [5], the wide availability of effective vaccines [6], and the development of diagnostic and preventive tools against influenza [7] and, more recently, Zika [8]. Bacterial diseases have profoundly impacted human health at different times in history, and although the phenomenon of antimicrobial resistance is a matter of extreme concern, there are several effective tools for the prevention, treatment, and diagnosis of bacterial infections [9]. Human parasitosis have been recognized to negatively impact public health in different parts of the globe for decades, which has stimulated the ongoing development of vaccines, new drugs, and diagnostic tests for malaria, sleeping sickness, leishmaniasis, filariasis, and Chagas disease [10]. Fungal infections, however, are part of a different scenario. These diseases, for most of recorded history as well as the majority of the last century, have been rare or had a low impact on human health. The increase in the number of immunocompromised patients, some of whom are highly susceptible to fungal infections, has totally changed this picture. The invasive diseases caused by fungi, the so-called systemic mycoses, profoundly impact human health. Moreover, the Global Action Fund for Fungal Infections (GAFFI) also highlights the devastating impact of focal fungal diseases in individuals who often have intact immune systems. GAFFI estimates that more than 1 million eyes go blind each year due to fungal keratitis [11]. Nearly one billion people have skin mycoses, which makes this disease only slightly less common on the planet than headaches and dental caries. Fungal spores contribute to significant reactive airway diseases in over 10 million individuals. In total, the GAFFI estimates that over 300 million people

The production of melanin significantly enhances the virulence of many important human pathogenic fungi. Despite fungal melanin’s importance in human disease, as well as melanin’s contribution to the ability of fungi to survive in diverse hostile environments, the structure of melanin remains unsolved. Nevertheless, ongoing research efforts have progressively revealed several notable structural characteristics of this enigmatic pigment, which will be the focus of this review. These compositional and organizational insights could further our ability to develop novel therapeutic approaches to combat fungal disease and enhance our understanding of how melanin is inserted into the cell wall.

Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect areas rich in keratin such as hair, nails and skin. Significantly, there are increasing rates of antimicrobial resistance among dermatophytes, especially for Trichophyton rubrum, the most frequent etiologic agent worldwide. Hence, investigators have been developing new therapeutic approaches, including photodynamic treatment. Photodynamic therapy utilizes a photosensitive substance activated by a light source of a specific wavelength. The photoactivation induces cascades of photochemicals and photobiological events that cause irreversible changes in the exposed cells. Although photodynamic approaches are well established experimentally for the treatment of certain cutaneous infections, there is limited information about its mechanism of action for specific pathogens as well as the risks to healthy tissues. In this work, we have conducted a comprehensive review of the current knowledge of photodynamic therapy as it specifically applies to fungal diseases. The data to date suggests that photodynamic treatment approaches hold great promise for combating certain fungal pathogens, particularly dermatophytes.

Talaromycosis (Penicilliosis) is an opportunistic mycosis caused by the thermally dimorphic fungus Talaromyces (Penicillium) marneffei. Similar to other major causes of systemic mycoses, the extent of disease and outcomes are the results of complex interactions between this opportunistic human pathogen and a host’s immune response. This review will highlight the current knowledge regarding the dynamic interaction between T. marneffei and mammalian hosts, particularly highlighting important aspects of virulence factors, intracellular lifestyle and the mechanisms of immune defense as well as the strategies of the pathogen for manipulating and evading host immune cells.

Staphylococcus aureus (SA) is a leading cause of a diverse spectrum of bacterial diseases, including abscesses. Nitric oxide (NO) is a critical component of the natural host defense against pathogens such as SA, but its therapeutic applications have been limited by a lack of effective delivery options. We tested the efficacy of a NO-releasing nanoparticle system (NO-np) in methicillin-resistant SA (MRSA) abscesses in mice. The results show that the NO-np exert antimicrobial activity against MRSA in vitro and in abscesses. Topical or intradermal NO-np treatment of abscesses reduces the involved area and bacterial load while improving skin architecture. Notably, we evaluated pro- and anti-inflammatory cytokines that are involved in immunomodulation and wound healing, revealing that NO-np lead to a reduction in angiogenesis preventing bacterial dissemination from abscesses. These data suggest that NO-np may be useful therapeutics for microbial abscesses.