Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been sweeping across the globe. Based on a retrospective analysis of SARS and ...influenza data from China and worldwide, we surmise that the fungal co-infections associated with global COVID-19 might be missed or misdiagnosed. Although there are few publications, COVID-19 patients, especially severely ill or immunocompromised, have a higher probability of suffering from invasive mycoses. Aspergillus and Candida infections in COVID-19 patients will require early detection by a comprehensive diagnostic intervention (histopathology, direct microscopic examination, culture, (1,3)-
β
-
d
-glucan, galactomannan, and PCR-based assays) to ensure effective treatments. We suggest it is prudent to assess the risk factors, the types of invasive mycosis, the strengths and limitations of diagnostic methods, clinical settings, and the need for standard or individualized treatment in COVID-19 patients. We provide a clinical flow diagram to assist the clinicians and laboratory experts in the management of aspergillosis, candidiasis, mucormycosis, or cryptococcosis as co-morbidities in COVID-19 patients.
•New Insights into immune mechanisms is key for developing anti-fungal vaccines and drugs.•Discussed pathogenesis of fungal pathogens & their interaction with host immune system.•Discussed the ...critical role of innate and adaptive immune cells that respond to IFI.•Emphasized the role of memory cells in long-term protection in subsequent infections.•Summarize the current vaccine strategies, co-infections studies and drug resistance.
The fungal infections are relatively common in humans that can range from common, mild superficial infections to life-threatening invasive infections. Most of the pathogenic fungi are opportunistic that cause disease under immunocompromised conditions such as HIV infection, cancer, chemotherapy, transplantation and immune suppressive drug users. Efficient detection and treatment of high-risk population remain the highest priority to avert most of the deaths. Majority of invasive infections are caused by Candida, Aspergillus and Cryptococcus species. Lack of effective vaccines, standardised diagnostic tools, efficient antifungal drugs and the emergence of drug-resistant species/strains pose a global threat to control Invasive fungal infections (IFI). A better understanding of the host immune response is one of the major approaches to developing new or improved antifungal strategies to control the IFIs. In this review, we have discussed pathogenesis of medically important fungi, fungal interaction with the host through pattern recognition receptors (PRRs) and the interplay of innate and adaptive immune cells in shaping host immunity to IFI. Further, we emphasized the role of memory cells by offering long-term protection in secondary or subsequent infections. Moreover, we depicted the role of unconventional innate-like immune cells in anti-fungal immunity. We also summarize the available information on the current vaccine strategies, genetic susceptibility to fungal infections, recent co-infections studies and the emergence of drug-resistance, a growing trend throughout the world. Finally, we emphasized the steps to be taken for the control of IFIs.
Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with
of the skin, nails, and mucous membrane. It is a rare and severe disease resulting from autoimmune ...defects or immune dysregulations. Nonetheless, the diagnosis and treatment of CMC still pose significant challenges. Erroneous or delayed diagnoses remain prevalent, while the long-term utility of traditional antifungals often elicits adverse reactions and promotes the development of acquired resistance. Furthermore, disease relapse can occur during treatment with traditional antifungals. In this review, we delineate the advancements in molecular diagnostic and therapeutic approaches to CMC. Genetic and biomolecular analyses are increasingly employed as adjuncts to clinical manifestations and fungal examinations for accurate diagnosis. Simultaneously, a range of therapeutic interventions, including Janus kinase (JAK) inhibitors, hematopoietic stem cell transplantation (HSCT), cytokines therapy, novel antifungal agents, and histone deacetylase (HDAC) inhibitors, have been integrated into clinical practice. We aim to explore insights into early confirmation of CMC as well as novel therapeutic options for these patients.
Malignant melanoma is the deadliest form of all skin cancers. Itraconazole, a commonly used systemic antifungal drug, has been tested for its anti-tumor effects on basal cell carcinoma, prostate ...cancer, and non-small cell lung cancer. Whether itraconazole has any specific anti-tumor effect on melanoma remains unknown. However, the goal of this study is to investigate the effect of itraconazole on melanoma and to reveal some details of its underlying mechanism. In the in vivo xenograft mouse model, we find that itraconazole can inhibit melanoma growth and extend the survival of melanoma xenograft mice, compared to non-itraconazole-treated mice. Also, itraconazole can significantly inhibit cell proliferation, as demonstrated by Ki-67 staining in itraconazole-treated tumor tissues. In in vitro, we show that itraconazole inhibits the proliferation and colony formation of both SK-MEL-28 and A375 human melanoma cells. Moreover, we demonstrate that itraconazole significantly down-regulates Gli-1, Gli-2, Wnt3A, β-catenin and cyclin D1, while it up-regulates Gli-3 and Axin-1, indicating potent inhibitory effects of itraconazole on Hedgehog (Hh) and Wnt signaling pathways. Furthermore, itraconazole significantly suppresses the PI3K/mTOR signaling pathway - indicated by the down-regulated phosphorylation of p70S6K, 4E-BP1 and AKT - but has no effect on the phosphorylation of MEK or ERK. Our data suggest that itraconazole inhibits melanoma growth through an interacting regulatory network that includes Hh, Wnt, and PI3K/mTOR signaling pathways. These results suggest that this agent has several potent anti-melanoma features and may be useful in the synergesis of other anti-cancer drugs via blockage of the Hh, Wnt and PI3K/mTOR signaling pathways.
Purpose
Since systematic antifungals for mucormycosis showed variable MICs depending on strains, effective and safe antifungal therapy was still needed. This study is aimed to evaluate the in vitro ...activity of doxycycline combined with antifungal therapy against dominant Mucorales pathogens.
Methods
Multidrug susceptibility testing was performed with doxycycline and antifungals, including itraconazole, posaconazole, and amphotericin, in 21 isolates of 8 dominant Mucorales pathogens.
Results
The fractional inhibitory concentration index according to M38 showed one
Rhizopus arrhizus
isolate synergic (
∑
FICI = 0.375) and other isolates in addition (0.5 <
∑
FICI < 4).
Conclusions
Doxycycline was found to have in vitro advantages in combined antifungal treatment over antifungals alone.
Adult tinea capitis is often neglected and misdiagnosed, especially in men. We herein reported an older man with seborrheic dermatitis-like tinea capitis caused by Trichophyton rubrum to raise ...awareness of the disease. Scale and alopecia were the critical diagnostic clues in this patient. Given the previous presence of tinea pedis and onychomycosis, relevant mycological examinations were promptly performed, and antifungal therapy, as well as patient education, were effectively administered.
Aspergillus fumigatus
(
A. fumigatus
) is the most common airborne opportunistic fungal pathogen. Biofilm formation is one of the main pathogenic mechanisms of
A. fumigatus
. During the past decades,
...A. fumigatus
azole resistance has become prevalent due to the medical and agricultural use of antifungal drugs and fungicides. Until now, the role of fungal biofilms in azole resistance of
A. fumigatus
remains unclear. In the present study, we compared biofilm drug susceptibility and biofilm formation under itraconazole of azole-resistant strains, sensitive strains, and standard strains, separately. The biofilm viability and matrix thickness at the early and the late stage were measured by XTT assay and Calcofluor white. Our results showed that the sessile minimum inhibitory concentration of itraconazole, which describing the inhibition of drugs on fungi sessile with biofilm, was much higher than the traditional minimal inhibitory concentration of itraconazole. Additionally, low concentrations of itraconazole inhibited biofilm formation of
A. fumigatus
strains. Notably, biofilm formation by azole-resistant strains could not be inhibited by high concentrations of itraconazole but could be effectively restrained by low concentrations of micafungin, revealing the efficacy of a cell-wall inhibitor to disrupt
A. fumigatus
biofilm formation. However, late-stage biofilms of both azole-resistant strains and standard strains were hard to disrupt using itraconazole. We found that itraconazole was effective to prevent
A. fumigatus
biofilm formation at the early stage. For the treatment of
A. fumigatus
biofilm, our findings suggest that an early-stage preventive strategy is preferred and micafungin is effective to control the azole-resistant strain infection.
Epidermophyton floccosum
is one of the most common agents of human superficial fungal infections, compared with genus
Trichophyton
and
Microsporum
, it possesses uniqueness in ecology traits and ...rarely causing hair infections.
E. floccosum
is so far the only representative species of genera
Epidermophyton
, and it is known as anthropophilic dermatophytes. To further reveal the genome sequences and clues of virulence factors, thus in this study, we sequenced the genome of
E. floccosum
(CGMCC (F) E1d), and performed comparative genomic analysis with other dermatophytes. It is revealed that
E. floccosum
owns the largest genome size and similar GC content compared with other dermatophytes. A total of 7565 genes are predicted. By comparing with the closest species
N. gypseum
, our study reveals that number and structure of adhesion factors, secreted proteases and LysM domain might contribute to the pathogenic and ecological traits of
E. floccosum
. Mating genes is also detected in genome data. Furthermore, we performed AFLP analysis trying to discuss intraspecific differences of
E. floccosum
, but no significant relationship is found between genotype and geographical distribution. Upon above, our study provides a deeper understanding and strong foundation for future researches about
E. floccosum
.
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