Medical mycology最新文献

Cryptococcus gattii is a fungal pathogen that poses significant threats to human health, affecting both immunocompromised and immunocompetent individuals. Treatment of C. gattii infections typically involves the use of antifungal agents, such as azoles. However, the increasing emergence of antifungal resistance in C. gattii is a growing concern, highlighting the critical need for novel therapeutic strategies. In our previous study, we identified a mitochondrial ATP-binding cassette (ABC) transporter, Atm1, as potentially involved in antifungal resistance in C. gattii through transcriptome sequencing, but its function remains unclear and requires additional confirmation and investigation. In this study, we developed a "suicide" clustered regularlyinterspaced short palindromic repeats-CRISPR-associated protein 9 system in C. gattii, based on the system used in C. neoformans, and successfully validated its functionality by targeting the ADE2 gene. We subsequently generated C. gattii mutants lacking ATM1 and assessed their growth under various stress conditions. Our data suggest that Atm1 is involved in the iron-sulfur cluster biosynthesis process. Besides, disruption of ATM1 resulted in various growth impairments, including reduced stress tolerance, impaired capsule formation, and diminished virulence. Importantly, we observed compromised antifungal drug resistance in the atm1∆ mutant and performed RNA sequencing-based transcriptome analysis and gene ontology analysis with and without antifungal treatment for further investigation. In conclusion, our findings indicate that ATM1 plays a role in iron homeostasis and is critical for antifungal resistance in C. gattii, offering new insights into potential drug development strategies for the clinical treatment of cryptococcosis.

Following the complete relaxation of Corona Virus Disease 2019 (COVID-19) epidemic control measures in China by the end of 2022, the number of patients with pulmonary mycosis admitted to hospitals across the country has exhibited a more pronounced upward trend. However, statistical data is lacking to determine whether there is a significant correlation between COVID-19 and pulmonary mycosis. This study collected baseline information, the first laboratory indicators after admission, the types of pathogens, and the prognosis data of patients with pulmonary fungal infections from a tertiary hospital in northern Anhui Province from January 1, 2017, to December 31, 2023, to reveal any association between COVID-19 infection and pulmonary fungal infections. The research results indicated that the G and GM test levels of patients who recovered from COVID-19 and those currently experiencing active infection with COVID-19 were significantly higher than those of patients with pulmonary fungal infections who had never been infected with COVID-19. Infection with COVID-19 and other viruses (excluding COVID-19), mechanical ventilation, and concurrent solid tumors were identified as independent risk factors for poor prognosis in patients with pulmonary fungal diseases. Among patients with viral infections, COVID-19 infection was the most common, with 25 cases (41.67%), followed by herpes simplex virus infection, with 15 cases (25.00%).

During an 11-month study at two hospital sites, 33 isolates initially classified as the Trichophyton mentagrophytes complex were subjected to whole-genome sequencing. Of these, 24 (72.7%) were identified as T. indotineae and 9 (27.3%) as T. interdigitale, with no T. mentagrophytes detected. Among the 22 patients with available clinical data, 75% exhibited involvement of multiple anatomical sites; although only two patients reported recent travel, 63.6% were migrant workers. Symptom resolution was documented in only four patients, whereas five experienced recurrences. Nearly 80% of T. indotineae isolates displayed terbinafine resistance linked to squalene epoxidase mutations, while no phenotypic azole resistance was observed, consistent with the absence of cyp51 mutations. Single-nucleotide polymorphism (SNP) analysis of both T. indotineae (520-1531 SNPs) and T. interdigitale (1380-115 963 SNPs) revealed no phylogenetic clustering, suggesting independent introductions.

Chromoblastomycosis (CBM) is a chronic fungal infection caused by dematiaceous fungi. In some cases, culture methods fail to identify the fungal species, and fresh tissue for molecular identification is unavailable. The use of molecular techniques on formalin-fixed, paraffin-embedded (FFPE) samples can aid in identifying the causative agent. This study aimed to identify fungal species in histopathologically confirmed cases of CBM using PCR and sequencing of 18S-ITS1-5.8S-ITS2-28S rDNA region of FFPE skin biopsies and to describe their clinicopathological features. This retrospective study used FFPE samples from nine CBM patients from remote regions of Mexico. The samples were submitted to the Mycology Section at the Hospital General "Dr. Manuel Gea González" (2000-2016) for molecular identification of the causative agent and characterization of clinicopathological features. Lesions were most commonly located on the forearm (four cases), with one case each on the buttock, back, foot, and leg. One patient presented with cutaneous dissemination. Verrucous plaques were observed in 88.9% of cases. Histology and direct examination confirmed CBM, showing muriform cells and varying degrees of dermal fibrosis in all cases. DNA extracted from FFPE samples was amplified and sequenced in the 18S-ITS1-5.8S-ITS2-28S rDNA region, identifying Fonsecaea pedrosoi with 100% homology in all cases. This study identifies F. pedrosoi as the predominant pathogen of CBM in the evaluated samples of Mexican origin and demonstrates the reliability of molecular identification using FFPE samples.

Long-term trends in the antifungal susceptibility of Talaromyces marneffei isolates have not been well characterized. We conducted a 40-year surveillance study analyzing the antifungal susceptibility of 131 T. marneffei isolates collected from the clinical laboratory of the First Affiliated Hospital of Guangxi Medical University between 1984 and 2024. In vitro susceptibilities to conventional antifungal agents, including itraconazole, voriconazole, fluconazole, and amphotericin B, were analyzed using the Clinical and Laboratory Standards Institute broth microdilution method. We also explored the potential influence of host Human Immunodeficiency Virus (HIV) status and fungal mating type (MAT) on susceptibility patterns. The minimum inhibitory concentrations (MICs) for itraconazole, voriconazole, fluconazole, and amphotericin B ranged from 0.015 to 0.06 μg/ml, 0.008 to 0.03 μg/ml, 1 to 8 μg/ml, and 0.25 to 1 μg/ml, respectively. Fluconazole showed a significant decline in susceptibility over time (P < .01), whereas the susceptibilities to the other antifungals remained stable (P > .05). The correlations observed between the MICs of different triazoles (P < .01) suggest potential cross-resistance among triazoles. MAT and HIV infection status did not significantly affect antifungal susceptibility patterns (P > .05). These findings underscore the importance of ongoing antifungal susceptibility surveillance in T. marneffei, considering the changes in fluconazole susceptibility and potential triazole cross-resistance, while other antifungals remain stable.

Cat-transmitted sporotrichosis (CTS) by Sporothrix brasiliensis is an important epizoonosis with alarming numbers of cases involving felines, canines, and humans. Considering the increasing incidence of CTS this study sought to elucidate the epidemiological characteristics of cats with sporotrichosis and evaluate the potential transmission routes of S. brasiliensis in several biological samples from cats with sporotrichosis. Samples were collected from ulcerated skin lesions, front paws, nasal cavity, and droplets collected from sick cats during sneezing episodes in a veterinarian university hospital, in the city of Curitiba, southern Brazil, between June 2021 and April 2022. A total of 100 cats with sporotrichosis were enrolled in the study. The fungus was isolated in 60% of samples from the nasal cavity and 71% of respiratory droplets. The growth of S. brasiliensis on the right and left front paw was observed in 41% of the cats included, and in 38%, there was growth of the fungus even without an apparent lesion on the paw. Of the infected cats, 64% had multifocal lesions throughout the body. The identification of S. brasiliensis in samples of exudate, paws, nasal cavity, and sneeze droplets suggests that transmission can occur not only through classic routes, but also through the movement of the infected cat, as well as through respiratory droplets expelled by the cat sneezing or nasal drip. Furthermore, the presence of S. brasiliensis on the paws of sick cats indicates the possibility that the fungus is being disseminated in the environment in which the animal lives.

We evaluated the characteristics and outcomes of ocular candidiasis in patients using buprenorphine intravenously. A retrospective analysis of 35 eyes of people who use drugs diagnosed with presumed ocular candidiasis between 2000 and 2017 was performed. Data on demographics, ocular findings, and microbiological results were extracted from medical records. Logistic regression was performed to identify factors of poor visual prognosis, then multivariate analysis used the variables that were statistically significant in univariate analysis. Most patients (83%) were male, with a mean duration of 7.1 ± 7.3 years from the onset of intravenous use of buprenorphine to diagnosis of ocular candidiasis. The mean best-corrected visual acuity (BCVA in logMAR) at diagnosis was 1.33 ± 0.73, improving significantly to 0.94 ± 0.91 at the last follow-up (P = .019). Diagnostic samples included aqueous humor from all patients and vitrectomy samples from 26 patients (74%), with positivity rates for Candida species culture of 23% and 27%, respectively. Extraocular sites tested positive for Candida in 54% of cases. Although representing 66% of identifications, Candida albicans was not the only identified organism. Treatment involved primarily fluconazole (91%) and intravitreal amphotericin B (69%). Poor visual outcomes correlated with low BCVA and presence of retinal detachment at baseline. Ocular candidiasis occurs in the context of chronic drug use. Diagnostic yield from ocular samples is relatively low, necessitating the investigation of extraocular infection sites or injection equipment. Poor baseline vision and retinal detachment were significant predictors of poor visual prognosis.

Tuberculosis (TB) and human immunodeficiency virus (HIV) represent important public health problems. Suppression of the immune system, due to both diseases, predisposes to the development of opportunistic infections, such as invasive fungal infections (IFI). The aims of this study were to determine the frequency of investigation of IFI in TB/HIV co-infected patients, identify the most frequent IFI and evaluate the clinical-epidemiological characteristics of TB/HIV/IFI patients. A descriptive and retrospective study was conducted including patients assisted at Hospital Dr. Miguel Riet Corrêa Jr. (HU-FURG/Ebserh), in Rio Grande City, southern Brazil. All patients diagnosed with TB/HIV from 2017 to 2022 were included, and databases were analyzed for data regarding mycological exams for fungal disease investigation. Of the 194 TB/HIV co-infected patients, 77.8% (n = 151) were investigated for at least one IFI. Co-infection was confirmed in 13.9% (21/151), being 52.4% (n = 11) of the patients diagnosed with cryptococcosis, followed by histoplasmosis (47.6%; n = 10) and probable invasive aspergillosis (IA) (9.6%; n = 2). Furthermore, some patients presented more than one fungal co-infection (9.5%; n = 2). CD4 T cell count < 200 cells/mm3 represented a risk factor for the development of IFI (P = 0.006) and the outcome death was higher in the TB/HIV/IFI group, as well as 38% of patients died. Even without a systematic investigation for IFI in TB/HIV patients, a high rate of co-infection was shown. Therefore, it is necessary to investigate TB and IFI concomitantly, in people living with HIV, due to the worsening of the outcome when these infections are associated.