Chitin is a polymer of N-acetylglucosamine and an essential component of the fungal cell wall. Chitosan is the deacetylated form of chitin and is also important for maintaining the integrity of this ...structure. Both polysaccharides are widely distributed in nature and have been shown to have a variety of applications in biomedicine, including their potential in immune sensing and as potential antifungal agents. In addition, chitin has been reported to play an important role in the pathogen-host interaction, involving innate and adaptive immune responses. This paper will explore the role of chitin and chitosan when incorporated into nanobiocomposites to improve their efficacy in detecting fungi of medical interest and inhibiting their growth. Potential applications in diagnostic and therapeutic medicine will be discussed, highlighting their promise in the development of more sensitive and effective tools for the early diagnosis of fungal infections. This review aims to highlight the importance of the convergence of nanotechnology and biology in addressing public health challenges.
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Fungal infections represent a constant and growing menace to human health, because of the emergence of new species as causative agents of diseases and the increment of antifungal drug resistance. ...Candidiasis is one of the most common fungal infections in humans and is associated with a high mortality rate when the fungi infect deep-seated organs. Candida krusei belongs to the group of candidiasis etiological agents, and although it is not isolated as frequently as other Candida species, the infections caused by this organism are of special relevance in the clinical setting because of its intrinsic resistance to fluconazole. Here, we offer a thorough revision of the current literature dealing with this organism and the caused disease, focusing on its biological aspects, the host-fungus interaction, the diagnosis, and the infection treatment. Of particular relevance, we provide the most recent genomic information, including the gene prediction of some putative virulence factors, like proteases, adhesins, regulators of biofilm formation and dimorphism. Moreover, C. krusei veterinary aspects and the exploration of natural products with anti-C. krusei activity are also included. Keywords: virulence, candidiasis, host-fungus interplay, antifungal drug, immune sensing
Fungal infections caused by
species have become a constant threat to public health, especially for immunocompromised patients, who are considered susceptible to this type of opportunistic infections.
...is known as the most common etiological agent of candidiasis; however, other species, such as
,
,
(previously known as
),
,
, and
(previously named as
), have also gained great importance in recent years. The increasing frequency of the isolation of this non-
species is associated with different factors, such as constant exposure to antifungal drugs, the use of catheters in hospitalized patients, cancer, age, and geographic distribution. The main concerns for the control of these pathogens include their ability to evade the mechanisms of action of different drugs, thus developing resistance to antifungal drugs, and it has also been shown that some of these species also manage to evade the host's immunity. These biological traits make candidiasis treatment a challenging task. In this review manuscript, a detailed update of the recent literature on the six most relevant non-
species is provided, focusing on the immune response, evasion mechanisms, and new plant-derived compounds with antifungal properties.
Sporotrichosis is known as a subacute or chronic infection, which is caused by thermodimorphic fungi of the genus
. It is a cosmopolitan infection, which is more prevalent in tropical and subtropical ...regions and can affect both humans and other mammals. The main etiological agents causing this disease are
,
, and
, which have been recognized as members of the
pathogenic clade. Within this clade,
is considered the most virulent species and represents an important pathogen due to its distribution and prevalence in different regions of South America, such as Brazil, Argentina, Chile, and Paraguay, and Central American countries, such as Panama. In Brazil,
has been of great concern due to the number of zoonotic cases that have been reported over the years. In this paper, a detailed review of the current literature on this pathogen and its different aspects will be carried out, including its genome, pathogen-host interaction, resistance mechanisms to antifungal drugs, and the caused zoonosis. Furthermore, we provide the prediction of some putative virulence factors encoded by the genome of this fungal species.
There is worldwide concern about the constant increase in infections caused by
species that are multiresistant to antifungal drugs. The most common candidiasis is caused by
, however, the species of ...the
complex and
are emerging opportunistic pathogens, which isolation from clinical samples has significantly increased in the past years. The special interest in the study of these species lies in their ability to evade the action of antifungal drugs, such as amphotericin B, azoles, and echinocandins. In addition, the phenotypic changes of these species have given them the ability to easily adapt to environmental changes, including the host milieu and immunity. In this paper, a detailed review of the current literature on the
complex and
is shown, analyzing aspects such as biology, immune response, putative virulence factors, infection, treatment, and the current strategies for diagnosis.
Sporotrichosis is a human and animal fungal infection distributed worldwide that is caused by the thermodimorphic species of the
pathogenic clade, which includes
,
, and
. The cell wall composition ...and the immune response against the
species have been studied mainly in
and
, whilst little is known about the
cell wall and the immune response that its components trigger. Therefore, in this study, we aimed to analyze the cell wall composition of
in three morphologies (germlings, conidia, and yeast-like cells) and the differences in cytokine production when human peripheral blood mononuclear cells (PBMCs) interact with these morphotypes, using
and
as a comparison. We found that
conidia and yeast-like cells have a higher cell wall chitin content, while all three morphologies have a higher β-1,3-glucan content, which was found most exposed at the cell surface when compared to
and
. In addition,
has lower levels of mannose- and rhamnose-based glycoconjugates, as well as of
- and
-linked glycans, indicating that this fungal cell wall has species-specific proportions and organization of its components. When interacting with PBMCs,
and
showed a similar cytokine stimulation profile, but with a higher stimulation of IL-10 by
. Additionally, when the inner cell wall components of
were exposed at the surface or
- and
-glycans were removed, the cytokine production profile of this species in its three morphotypes did not significantly change, contrasting with the
and
species that showed different cytokine profiles depending on the treatment applied to the walls. In addition, it was found that the anti-inflammatory response stimulated by
was dependent on the activation of dectin-1, mannose receptor, and TLR2, but not TLR4. All of these results indicate that the cell wall composition and structure of the three
species in the three morphologies are different, affecting their interaction with human PBMCs and generating species-specific cytokine profiles.
Protein glycosylation is a highly conserved post-translational modification among organisms. It plays fundamental roles in many biological processes, ranging from protein trafficking and cell ...adhesion to host–pathogen interactions. According to the amino acid side chain atoms to which glycans are linked, protein glycosylation can be divided into two major categories: N-glycosylation and O-glycosylation. However, there are other types of modifications such as the addition of GPI to the C-terminal end of the protein. Besides the importance of glycoproteins in biological functions, they are a major component of the fungal cell wall and plasma membrane and contribute to pathogenicity, virulence, and recognition by the host immunity. Given that this structure is absent in host mammalian cells, it stands as an attractive target for developing selective compounds for the treatment of fungal infections. This review focuses on describing the relationship between protein glycosylation and the host–immune interaction in medically relevant fungal species.
Fungal infections represent a worldwide concern for public health, due to their prevalence and significant increase in cases each year. Among the most frequent mycoses are those caused by members of ...the genera Candida, Cryptococcus, Aspergillus, Histoplasma, Pneumocystis, Mucor, and Sporothrix, which have been treated for years with conventional antifungal drugs, such as flucytosine, azoles, polyenes, and echinocandins. However, these microorganisms have acquired the ability to evade the mechanisms of action of these drugs, thus hindering their treatment. Among the most common evasion mechanisms are alterations in sterol biosynthesis, modifications of drug transport through the cell wall and membrane, alterations of drug targets, phenotypic plasticity, horizontal gene transfer, and chromosomal aneuploidies. Taking into account these problems, some research groups have sought new therapeutic alternatives based on drug repositioning. Through repositioning, it is possible to use existing pharmacological compounds for which their mechanism of action is already established for other diseases, and thus exploit their potential antifungal activity. The advantage offered by these drugs is that they may be less prone to resistance. In this article, a comprehensive review was carried out to highlight the most relevant repositioning drugs to treat fungal infections. These include antibiotics, antivirals, anthelmintics, statins, and anti-inflammatory drugs.Fungal infections represent a worldwide concern for public health, due to their prevalence and significant increase in cases each year. Among the most frequent mycoses are those caused by members of the genera Candida, Cryptococcus, Aspergillus, Histoplasma, Pneumocystis, Mucor, and Sporothrix, which have been treated for years with conventional antifungal drugs, such as flucytosine, azoles, polyenes, and echinocandins. However, these microorganisms have acquired the ability to evade the mechanisms of action of these drugs, thus hindering their treatment. Among the most common evasion mechanisms are alterations in sterol biosynthesis, modifications of drug transport through the cell wall and membrane, alterations of drug targets, phenotypic plasticity, horizontal gene transfer, and chromosomal aneuploidies. Taking into account these problems, some research groups have sought new therapeutic alternatives based on drug repositioning. Through repositioning, it is possible to use existing pharmacological compounds for which their mechanism of action is already established for other diseases, and thus exploit their potential antifungal activity. The advantage offered by these drugs is that they may be less prone to resistance. In this article, a comprehensive review was carried out to highlight the most relevant repositioning drugs to treat fungal infections. These include antibiotics, antivirals, anthelmintics, statins, and anti-inflammatory drugs.
Sporotrichosis is a cutaneous mycosis that affects humans and animals and has a worldwide distribution. This infection is mainly caused by Sporothrix schenckii, Sporothrix brasiliensis, and ...Sporothrix globosa. Current research about anti-Sporothrix immunity has been mainly focused on S. schenckii and S. brasiliensis, using different types of human or animal immune cells. Granulocytes are a group of cells relevant for cytokine production, with the capacity for phagocytosis and the generation of neutrophil extracellular traps (NETs). Considering their importance, this study aimed to compare the capacity of human granulocytes to stimulate cytokines, uptake, and form NETs when interacting with different Sporothrix species. We found that conidia, germlings, and yeast-like cells from S. schenckii, S. brasiliensis, and S. globosa play an important role in the interaction with these immune cells, establishing morphology- and species-specific cytokine profiles. S. brasil-iensis tended to stimulate an anti-inflammatory cytokine profile, whilst the other two species had a proinflammatory one. S. globosa cells were the most phagocytosed cells, which occurred through a dectin-1-dependent mechanism, while the uptake of S. brasiliensis mainly occurred via TLR4 and CR3. Cell wall N-linked and O-linked glycans, along with β-1,3-glucan, played a significant role in the interaction of these Sporothrix species with human granulocytes. Finally, this study indicates that conidia and yeast-like cells are capable of inducing NETs, with the latter being a better stimulant. To the best of our knowledge, this is the first study that reports the cytokine profiles produced by human granulocytes interacting with Sporothrix cells.
The incidence of fungal infections is increasing at an alarming rate and has posed a great challenge for science in recent years. The rise in these infections has been related to the increase in ...immunocompromised patients and the resistance of different species to antifungal drugs. Infections caused by the different Candida species, especially Candida albicans, are one of the most common mycoses in humans, and the etiological agents are considered opportunistic pathogens associated with high mortality rates when disseminated infections occur. Candida lusitaniae is considered an emerging opportunistic pathogen that most frequently affects immunocompromised patients with some comorbidity. Although it is a low-frequency pathogen, and the mortality rate of C. lusitaniae-caused candidemia does not exceed 5%, some isolates are known to be resistant to antifungals such as amphotericin B, 5- fluorocytosine, and fluconazole. In this paper, a detailed review of the current literature on this organism and its different aspects, such as its biology, possible virulence factors, pathogen-host interaction, diagnosis, and treatment of infection, is provided. Of particular interest, through Blastp analysis we predicted possible virulence factors in this species. Keywords: biological aspects, candidiasis, multidrug resistance, opportunistic pathogens, virulence factors
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