Medical mycology最新文献

In recent years, the resistance of Sporothrix globosa to antifungal treatments has steadily increased, while the cure rate for sporotrichosis has declined. This growing resistance underscores the urgent need to develop novel antifungal agents with distinct mechanisms of action. Previous studies have demonstrated that phosundoxin, a biphenyl aliphatic amide that targets mitochondria, exhibits potent inhibitory effects against a broad spectrum of fungi. To further evaluate its antifungal activity, we conducted drug susceptibility testing on 112 S. globosa strains and compared the results with those of conventional antifungal agents. Phosundoxin consistently exhibited antifungal activity against all tested strains, including both mycelial forms and 32 yeast-phase strains, at concentrations ranging from 1 to 4 µg/ml. Notably, in itraconazole-resistant S. globosa strains, phosundoxin treatment led to the identification of 553 differentially expressed genes and 273 differentially expressed proteins. Integrated Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that phosundoxin exerts its antifungal effects by disrupting the mitochondrial respiratory chain and oxidative phosphorylation. This disruption triggers cellular stress responses, including the upregulation of ammonia transport and nitrogen metabolism. Additionally, phosundoxin treatment weakens cellular defense mechanisms, interferes with the cell cycle, and inhibits protein synthesis-ultimately leading to negative regulatory effects and cell death. These findings highlight phosundoxin's potential as a novel antifungal agent for treating S. globosa infections and provide critical insights into its mechanism of action against this pathogen.

Mucormycosis is an invasive fungal infection with very high mortality in patients with diabetic ketoacidosis, iron overload, or immune suppression. Rhizopus and Mucor are the most common etiological agents, with rhino-orbital-cerebral mucormycosis being the most frequent form of the disease. In this study, we sought to determine the activation of apoptosis, necroptosis, ferroptosis, and pyroptosis along with oxidative stress markers, in formalin-fixed paraffin embedded rhino-orbital tissues from patients with mucormycosis and COVID-19-Associated-Mucormycosis (CAM). We observed increased expression of 3-nitrotyrosine and phosphorylated Nuclear factor Erythroid 2-related factor 2, suggesting the presence of oxidative stress in these tissues. Elevated levels of CD71, phosphorylated MLKL (Mixed lineage kinase domain-like protein), and cleaved caspase 3 were detected in both mucormycosis and CAM tissues, indicating differential activation of ferroptosis, necroptosis and apoptosis during fungal infection. Notably, cleaved gasdermin D was not detected, indicating that pyroptosis does not play a significant role in mediating host lytic cell death during invasive mucormycosis. Our findings, which identify differential activation of programmed cell death pathways directly in human tissues, meet an important critical gap in the mucormycosis literature and highlight viable targets for future therapeutic interventions.

Candidemia cases increased during the COVID-19 pandemic, likely due to increased critical care interventions. However, the pandemic's impact on candidemia risk factors and outcomes remains understudied. The objective of this study was to evaluate changes in candidemia risk factors and in-hospital mortality before and during the COVID-19 pandemic, stratified by COVID-19 status. We retrospectively analyzed adult candidemia cases (defined by Candida species isolated from blood cultures) at a single center in Albany, Georgia, USA (January 2017-May 2023). Patients were grouped as (1) pre-pandemic, (2) pandemic with COVID-19, and (3) pandemic without COVID-19. Clinical characteristics, risk factors, and in-hospital mortality were compared across groups. Among 89 patients (44% pre-pandemic, 56% pandemic [50% with COVID-19]), comorbidities were highest pre-pandemic (P = .008), though 12% of patients with COVID-19 had none (vs. 0% pre-pandemic, 4% non-COVID-19; P = .01). Candidemia was more often diagnosed in the ICU among the COVID-19 group (92%) compared to pre-pandemic (49%) and non-COVID-19 pandemic groups (44%) (P < .001). Mechanical ventilation (88%) and vascular catheter use (96%) were also higher in the COVID-19 group (P < .001 for both). Glucocorticoid use was more frequent in the COVID-19 group (76%) versus pre-pandemic (18%) and non-COVID-19 pandemic groups (24%) (P = .008). In-hospital mortality was highest in the COVID-19 group (76%) compared to the pre-pandemic (44%) and non-COVID-19 pandemic groups (32%) (P < .001). Patients with COVID-19 had a higher prevalence of risk factors for candidemia and significantly worse clinical outcomes, including increased in-hospital mortality, compared to other groups.

Sporothrix brasiliensis, an emerging fungal threat, is spreading through South America with more than five countries in the Americas now reporting cases. Compared to other species, S. brasiliensis is more virulent, and its primary transmission route to humans is from direct contact with infected cats. The increasing number of cases across South America and the challenges in preventing zoonotic transmission pose a significant and growing public health concern. On November 23, 2024, the International Society for Human and Animal Mycology One Health Sporotrichosis Working Group held a symposium to discuss current challenges and potential strategies. This article represents an overview of the discussions that occurred during the symposium focusing on four broad categories: identifying and monitoring introduction of S. brasiliensis in new regions; diagnosis; treatment of humans and cats; preventing and controlling the spread of S. brasiliensis. Overarching themes from all four categories included a gap in the scientific understanding needed to effectively guide public health action and clinical care and the need for multidisciplinary collaboration to address the problem. A better understanding of the epidemiology, including transmission, and optimal diagnostics and clinical treatments, is needed. Public health activities with a One Health approach, including surveillance, health education, prevention, and control efforts, may benefit from innovative strategies that involve microbiologists, veterinarians, physicians, and public health officials.

Candidemias caused by the yeasts formerly encompassed as Candida spp. require expedited identification to decide on the antifungal treatment and reduce mortality. Traditional methods rely on subcultures for diagnosis, with turnaround times of 72-96 h, or expensive equipment. Deep learning and convolutional neural networks (CNN) have shown high accuracy for image recognition in microbiology. We compared the accuracy of six CNNs (GoogLeNet, InceptionV3, AlexNet, ResNet18, ResNet50, and DenseNet161) to identify Candida spp. at the species level, with photographs obtained mainly from clinical blood cultures showing yeast structures in the Gram stain, which were identified as Candida spp. in the subculture. Images were obtained from January 2012 to May 2024 and stored in the image databank of two third-level teaching hospitals in Mexico City. We analyzed the five most frequent species from both centers' clinical samples and included simulated blood culture images from Candida auris (Candidozyma auris) and C. krusei (Pichia kudriavzevii) strains. After processing and segmentation, we loaded the CNNs with 531 whole photographs and 2804 patches. The CNN Densnet161, using a scan-based approach, showed higher accuracy identifying 87%, 99%, 94%, 100%, 89%, and 95% of the images containing C. albicans, C. auris, C. glabrata (Nakaseomyces glabrata), C. krusei (P. kudriavzevii), C. parapsilosis, and C. tropicalis, respectively. These results show that CNN image recognition can identify clinically relevant Candida spp. directly from positive Gram-stained smears, which may help make early decisions for antifungal treatment.

Cats attended at a veterinary clinic in Magallanes, Chile, were screened for Sporothrix brasiliensis in their claws. Five of 140 screened cats were positive, with three of them being symptomatic. Increased awareness of S. brasiliensis circulating in Chile could help take precautions to prevent feline outbreaks and human infection.

Sporotrichosis is a neglected subcutaneous mycosis of global distribution caused by thermally dimorphic Sporothrix species. Despite their pathogenic potential in vertebrates, the virulence mechanisms underlying their interactions with other organisms remain poorly understood. This study employed the coleopteran insect Tenebrio molitor as an experimental model to evaluate the virulence of seven Sporothrix species from clinical (S. brasiliensis, S. schenckii, S. globosa, S. luriei) and environmental (S. pallida, S. mexicana, S. chilensis) clades. Larvae were inoculated with conidia or yeast cells and assessed for survival, fungal burden (colony-forming units), histopathology, hemocyte count, and antimicrobial peptide (AMP) gene expression. Virulence patterns in this model paralleled those observed in mammalian hosts, with S. schenckii and S. brasiliensis showing higher virulence (30-40% larval survival). Distinct profiles were observed between fungal phases, the yeast phase generally showing increased virulence. Interestingly, contrary to murine models, environmental species S. pallida and S. chilensis exhibited unexpectedly high virulence in the mycelial phase (larval survival of 30% and 10%, respectively). Additionally, AMP genes (Thaumatin-like 1 and Tenecin 3) were more strongly expressed in larvae infected with S. brasiliensis and S. pallida. These findings suggest that the T. molitor immune response to Sporothrix may be influenced by the evolutionary history of both the host and the fungal genus. Overall, our results highlight the intricate relationship between fungal virulence, host immunity, and ecological factors shaping the outcome of Sporothrix infections in T. molitor.

Microsporidia are obligate intracellular eukaryotic parasites, phylogenetically related to fungi, and are recognised causes of significant morbidity in humans. They are opportunistic pathogens of particular concern in HIV-infected and other immunocompromised populations. In this study, the occurrence and genetic diversity of microsporidian infections (Enterocytozoon bieneusi and Encephalitozoon spp.) were investigated in socially vulnerable populations from disadvantaged areas in southern Madagascar. Epidemiological questionnaires were used to collect demographic data and potential risk factors. Faecal samples (n = 436) from 318 children and adolescents (7-21 years), 57 young mothers (16-21 years), and 61 of their infants (0-5 years) were collected and analysed using molecular methods (PCR and Sanger sequencing). Only E. bieneusi infections were detected, with an overall prevalence of 3.0% (95% CI: 1.6-5.0). The highest prevalence was observed in young mothers (3.5%; 95% CI: 0.4-12.1), nearly followed by infants (3.3%; 95% CI: 0.4-11.4). Genotyping of E. bieneusi was successfully performed in 11 of the 13 positive samples, identifying five known genotypes (A, CAF1, D, PigEBITS7, and Type IV) and one novel genotype, designated HhMdEb1. The most frequently detected genotypes were A and CAF1. All genotypes identified, including the novel genotype, belong to Group 1, which is characterised by low host specificity and high zoonotic potential. The detection of genotypes commonly associated with animal hosts suggests both zoonotic and anthroponotic transmission pathways. These findings underscore the need to implement integrated control strategies within the framework of the 'One Health' approach.

A predominant fluconazole-resistant Candida tropicalis clade 4 genotype, based on MLST analysis, causing candidemia in humans in several tropical countries, was detected in the environment in a 2012 orchard survey in Taiwan, which is an emerging one health issue. This follow-up study investigated clade 4 azole-resistant C. tropicalis in orchards, comparing the 2012 survey data with the 2018 survey findings. We compared C. tropicalis isolated from the same 53 orchards, including 23 wax apple, 17 grape, and 13 papaya orchards, in both the 2012 and 2018 surveys. We collected samples of fruits, soils, and irrigation water from environment and swab samples from armpit and hand, as well as oral mouth rinses of the farmers. Overall, the rate of fluconazole-resistant C. tropicalis from the 2018 survey was significantly higher than that from the 2012 survey (27/55 vs. 9/46, P = .003). Furthermore, we found that the use of azole fungicides was associated with the detection of azole-resistant C. tropicalis. Notably, 77.8% (7/9) of the azole-resistant isolates in the 2012 survey and 92.6% (25/27) in the 2018 survey were genetically related and belonged to the clade 4 genotype. Our findings demonstrate that the rate of fluconazole-resistant C. tropicalis from orchards increased significantly and the clade 4 drug-resistant C. tropicalis spread widely in orchard environments, especially among grape ones. Our findings show that different types of crop had different cultivation habits. Hence, grape orchard environment is a priority to conduct intervention for cultivation habits of farmers, especially on azole fungicide use in Taiwan.

Knowledge of the clinical recognition and management of osteoarticular sporotrichosis is derived from case reports and limited series. Our aim was to perform a systematic review to evaluate the differences in epidemiologic and clinical findings between localized and systemic forms of osteoarticular sporotrichosis. We searched MEDLINE/PubMed, SCOPUS, Web of Science (WoS), Ovid, SCiELO, Cochrane, China National Knowledge Infrastructure (CNKI), Wanfang Data, CQVIP, and xueshu.baidu.com on December 31, 2023. The retrieved case data was divided into two groups: (1) localized osteoarticular infection and (2) systemic osteoarticular infection. We estimated differences between the two groups using generalized linear models with Poisson distribution for robust variances to estimate prevalence ratios (PRs) with 95% confidence intervals (95% CIs). A total of 111 cases of localized infection and 100 cases of systemic infection were included. Individuals with systemic infection were more likely to be from hyperendemic areas (adjusted prevalence ratio (aPR) = 1.64; 95% CI, 1.24-2.18; P = .001), have HIV infection (aPR = 2.33; 95% CI, 1.42-3.82; P = .001), and have cancer (aPR = 1.90; 95% CI, 1.09-3.31; P = .023). Arthritis (50.4%) and osteomyelitis (46.0%) were predominant in localized and systemic infections, respectively. Osteomyelitis in two or more bones was more common in individuals with a systemic infection (aPR = 10.3; 95% CI, 3.38-31.7; P < .0001). Most cases of localized infection were treated with combination antifungals and surgery (32.2%), combination antifungals (25.3%) and amphotericin B monotherapy (19.1%), and systemic infection with combination antifungals (49.4%). As for the outcome, there were better outcomes in localized than in systemic infection. Therefore, Sporothrix infection should be considered in the differential diagnosis of osteomyelitis or arthritis, especially in immunocompromised patients from hyperendemic areas.