Mycopathologia最新文献

Background: Traditional methods for diagnosing onychomycosis are characterized by limited sensitivity and prolonged processing times, and heavily rely on the skill level of laboratory personnel.

Objectives: To develop a fast, simple, user-friendly, and reliable molecular assay that offers high sensitivity and specificity for the detection of common dermatophytes in nail specimens.

Methods: We developed a technique that integrates recombinase polymerase isothermal amplification with lateral flow dipstick (RPA-LFD) for the detection of pan-dermatophytes and Trichophyton rubrum, and evaluated its analytical sensitivity and specificity. This method was applied to analyze 190 nail specimens, with the results compared with traditional microscopy and fungal culture.

Results: The RPA-LFD assay demonstrated an analytical sensitivity of 10 pg/reaction for pan-dermatophytes and 1 pg/reaction for T. rubrum. In clinical evaluations for tinea unguium, the sensitivity of the RPA-LFD, fungal culture, and microscopy methods, as determined through latent class analysis, was estimated to be 91.0%, 70.8%, and 93.9%, respectively. Correspondingly, the specificity of these methods-RPA-LFD, fungal culture, and microscopy-was assessed at approximately 95.7%, 98.0%, and 94.3%.

Conclusions: Our RPA-LFD assay exhibited high sensitivity and specificity in the detection of dermatophytes. Due to its technical simplicity, enhanced sensitivity, and reduced processing times, it represents a promising alternative to conventional fungal culture methods for the mycological detection and identification of dermatophytes.

The sudden emergence of multidrug- and pan-resistant Candida auris isolates, combined with limited treatment options, poses significant global challenges in healthcare settings. Combination based therapies are promising alternative options to overcome C. auris related infections, where echinocandin and isavuconazole (ISA) combinations may be an interesting and promising approach. Understanding the molecular mechanisms underlying ISA treatment is crucial for developing novel therapeutic recommendations. Therefore, we investigated the gene transcription profiles of non-wild type (non-WT) and wild type (WT) C. auris isolates from the South Asian clade following ISA exposure using total RNA sequencing. The non-WT isolate was classified according to the previously reported tentative epidemiological cut-off value of ≤ 1 mg/L. ISA treatment resulted in the upregulation of 158 and 134 genes and the downregulation of 119 and 96 genes in the non-WT and WT isolates, respectively, compared with untreated samples. In general, ISA-treated isolates exhibited increased transcription of the transcriptional factor UPC2, the drug transporter MDR1, vacuolar calcium-ATPase PMC1, and several ergosterol biosynthesis genes. The WT isolate showed pronounced enrichment of genes involved in sphingolipid biosynthesis, adhesion, and drug transport. These findings suggest that alterations in membrane lipid composition and modulation of drug efflux transporters are critical processes contributing to ISA susceptibility in case of WT isolates.

We presented a case of chronic mucocutaneous candidiasis (CMC) due to STAT1 GOF mutation with recurrent enteritis and intestinal obstruction. A 33-year-old woman complained of recurrent oral erosion and finger (toe) nails damage for over 30 years. Candida albicans were cultured from the oral mucosa and nails. Sanger sequencing revealed a gain-of-function mutation in STAT1 (c.A1159 G, p.T387A). Since the age of 37, she developed recurrent enteritis and intestinal obstruction. Laboratory examinations revealed an increased pSTAT1 protein expression and a decreased proportion of Th17 cells in peripheral blood lymphocyte (PBMC), with a high expression of pSTAT1 and scarce expression of IL17A observed in intestinal immunohistochemistry. Intestinal obstruction had not previously been reported as the main clinical manifestation in STAT1 GOF patients. We speculated that the low levels of IL17A impaired the intestinal barrier, which might lead to gastrointestinal disorders in this patient. This case expanded the clinical phenotype of heterozygous STAT1 GOF patients.

Pulmonary surfactant, the primary substance lining the epithelium of the human Lower Respiratory Tract (LRT), is rich in lipids, with dipalmitoyl-phosphatidylcholine (DPPC) being the most abundant. Although surfactants are known to have antifungal activity against some yeast species, the significant presence of species like Malassezia restricta in the lung mycobiome suggests that these yeasts may exhibit some level of lipo-tolerance or even lipo-affinity for pulmonary lipids. This study explored the affinity and tolerance of yeasts, identified as significant members of the lung microbiome, to pulmonary lipids through culture-based methods. Eleven species from the genera Malassezia, Candida (including the new genera Nakaseomyces and Meyerozyma), and Cryptococcus were tested for their growth on media containing pulmonary lipids such as DPPC and commercial porcine surfactant and in other culture medium that contain non-pulmonary lipids such as glycerol monostearate and tweens. The yeasts' lipo-affinity or lipo-tolerance was assessed based on their growth on these lipids compared to standard media, specifically Modified Leeming Notman Agar (MLNA) for Malassezia species and Sabouraud Dextrose Agar (SDA) for the other genera. The addition of DPPC or surfactant to the media enhanced the growth of most Malassezia yeasts and some Cryptococcus species. C. parapsilosis, Meyerozyma guilliermondii and Cryptococcus neoformans s.s. showed similar growth to that on the standard media, while the other yeasts primarily demonstrated lipo-tolerance without lipo-affinity for these compounds. To our knowledge, this is the first report on the influence of pulmonary lipids on the in vitro growth of Malassezia spp. and other yeast members of the lung mycobiome. Some yeasts, such as Malassezia restricta, commonly found in the lower respiratory tract (LRT), exhibit specific affinity for lung lipids like DPPC and commercial porcine surfactant. This finding suggests that lung lipids may play a significant role in shaping the LRT mycobiome.

During the last two decades, wound invasive fungal diseases (WIFDs) have reemerged as important causes of mortality and morbidity in military personnel and civilian casualties in war areas. Historically, mycotic infections acquired in combat operations during Vietnam War and were associated with burn wounds. Modern combat related WIFDs are almost exclusively associated with severe traumatic events which encompass blast exposure as the primary mechanism of injury and subsequent extremity amputation and extensive blood loss. Such infections often lead to deep tissue necrosis, long hospitalizations, extensive surgeries, and more severe amputation. Studies of combat related WIFDs among U.S. military personnel in Operation Enduring Freedom (Afghanistan) demonstrated incidence rates of approximately 7% and crude mortality of 8.5%. WIFDs were also seen in U.K. military personnel returning from Afghanistan and are common in the current Ukraine and Gaza conflicts. Mucorales, Aspergillus and Fusarium species are the predominant causes of WIFDs. These molds are opportunistic pathogens which thrive in patients with immune system imbalances following traumatic injury. They are ubiquitous environmental fungi found in a variety of soils but there are significant regional differences depending on the local soil type, vegetation, and climate. The management of WIFDs is complicated by the limited efficacy of current antifungals on many of these environmental species and by emerging antifungal resistance globally. This review provides an overview of the global burden, epidemiology, and clinical features of combat-related fungal infections with the aim to provide a better understanding of the threat posed for wounded Service Members and civilians.

Dermatophytes represent the largest and most common group of fungal infections, impacting 25% of the global population. Among them, Trichophyton rubrum has emerged as the predominant species, responsible for a range of conditions such as tinea corporis, tinea pedis, onychomycosis, tinea cruris, and tinea manuum. Although dermatophyte incidence varies geographically, there is a noticeable rise in cases caused by T. indotineae, a strain that exhibits resistance to terbinafine. In the past decade zoophilic dermatophyte T. mentagophytes genotype VII (now known as T. interdigitale) gains a growing importance, due to its increasing frequency, the severity of the clinical manifestation and mode of transmission. Tinea infections present with various clinical symptoms and can affect individuals of all ages, from tinea pedis in adults to tinea capitis in children. Among adults globally, tinea unguium (onychomycosis) is the most common form of dermatophytosis, affecting 5.5% of the general population. Tinea unguium is more frequently seen in developed countries, while tinea capitis is more common in developing nations. The COVID-19 pandemic has led to an increase in cases of tinea faciei, likely due to prolonged mask-wearing. Terbinafine remains the preferred treatment for dermatophyte infections worldwide due to its potent fungicidal properties, minimal risk of drug interactions, and fewer side effects compared to other oral antifungals. Itraconazole and terbinafine appear to be equally effective and safe for treating tinea cruris and tinea corporis. However, the rising resistance of dermatophytes to these antifungal drugs, along with frequent recurrences of dermatophytosis in certain regions, is becoming a significant public health concern.

Mucormycosis is an invasive fungal infection, caused by fungi of the order Mucorales, and it is associated with high morbidity and mortality. The epidemiology of mucormycosis is evolving. The incidence, underlying risk factors, clinical presentation, as well as the responsible mucoralean agents, vary by geographic region. The estimated incidence in developed countries ranges from less than 0.06 to 0.3 cases per 100,000 population per year, while in India, it reaches approximately 14 cases per 100,000 population per year, which is about 80 times higher. In European countries the estimated incidence ranges from less than 0.04 to 0.12 per 100,000 population per year. Diabetes mellitus (DM) is the leading underlying disease globally. In Europe, hematological malignancies are the most common risk factor for mucormycosis, while in Asia diabetes predominates. The rhino-cerebral form of mucormycosis is most commonly seen in patients with DM, whereas pulmonary mucormycosis in patients with hematological malignancies and transplants. The most common species globally is Rhizopus arrhizus, whereas new emerging species only occasionally cause infection in Europe. However, vigilance is required, as they may raise concerns-especially in light of climate change- due to their potential to cause serious infections in both immunocompetent and immunosuppressed individuals.