Medical Mycology

Bronchoalveolar lavage fluid (BALF) is a standard respiratory sample for diagnosing invasive fungal diseases like Pneumocystis pneumonia (PCP) and invasive pulmonary aspergillosis (IPA). However, procedural variations exist across medical centers and wards. This study aimed to compare the diagnostic potential of BALF and bronchial aspirate (BA) obtained during bronchoscopy in 173 patients suspected of fungal infections. A prospective observational study was conducted from April 2020 to November 2021. BALF and BA were collected during bronchoscopy and subjected to direct examination, fungal culture, Aspergillus fumigatus qPCR (AfqPCR), and Pneumocystis jirovecii qPCR (PjqPCR)...

Antifungal drug resistance is an emerging cause of treatment failure in invasive fungal infections, and antifungal susceptibility testing (AFST) may inform treatment decisions. Currently, there are no established AFST guidelines for Talaromyces marneffei (Tm) or other dimorphic fungi. We developed a colorimetric AFST method using a fluorescent redox indicator alamarBlue, which changes from blue to pink in proportion to cellular metabolic activity. We determined the optimal time for alamarBlue addition to be 24 h post-inoculation and for MIC reading to be 72 h post-inoculation...

Although previous studies on the genotypic diversity and antifungal susceptibility of the Cryptococcus neoformans species complex (CNSC) isolates from China revealed ST5 genotype isolates being dominant, the information of the CNSC isolates from Chinese HIV-infected patients is limited. In this study, 171 CNSC isolates from HIV-infected patients in the Chongqing region of Southwest China were genotyped using the International Society for Human and Animal Mycology-multilocus sequence typing (ISHAM-MLST) consensus scheme, and their antifungal drug susceptibilities were determined following CLSI M27-A3 guidelines...

Germline-encoded pattern recognition receptors (PRRs), particularly C-type lectin receptors (CLRs), are essential for phagocytes to sense invading fungal cells. Among CLRs, Dectin-2 (encoded by Clec4n) plays a critical role in the antifungal immune response as it recognizes high-mannose polysaccharides on the fungal cell wall triggering phagocyte functional activities and ultimately determines adaptive responses. Here, we assessed the role of Dectin-2 on the course of primary Paracoccidioides brasiliensis systemic infection in mice with Dectin-2-targeted deletion...

Mycetoma is a neglected tropical disease commonly caused by the fungus Madurella mycetomatis. Standard treatment consists of extensive treatment with itraconazole, in combination with surgical excision of the infected tissue, but has a low success rate. To improve treatment outcomes, novel treatment strategies are needed. Here, we determined the potential of manogepix, a novel antifungal agent which targets the GPI-anchor biosynthesis pathway by inhibition of the GWT1 enzyme. Manogepix was evaluated by determining the Minimal Inhibitory Concentrations (MICs) according to the CLSI based in vitro susceptibility assay for 22 M...

Cryptococcal meningitis is the second most common cause of death in people living with HIV/AIDS, yet we have a limited understanding of how cryptococcal isolates change over the course of infection. Cryptococcal infections are environmentally acquired, and the genetic diversity of these infecting isolates can also be geographically linked. Here, we employ whole genome sequences for 372 clinical Cryptococcus isolates from 341 patients with HIV-associated cryptococcal meningitis obtained via a large clinical trial, across both Malawi and Cameroon, to enable population genetic comparisons of isolates between countries...

Histoplasmosis, the most common endemic mycosis in North America, presents in a myriad of ways, spanning the spectrum from self-limiting pneumonia to progressive disseminated histoplasmosis (PDH). Towards better describing contemporary histoplasmosis syndromes, risks, and outcomes, this single-center retrospective cohort study was performed (2009-2019). The population that developed PDH was similar to that with other forms of histoplasmosis (OFH) except for higher rates of preexisting immunocompromising conditions (91...

Ethyl caffeate (EC) is a phenylpropanoid compound derived from Elephantopus scaber. In our previous work, EC was investigated to have a strong synergistic antifungal effect against azole-resistant strains of Candida albicans when combined with fluconazole (FLU). However, the protective effect and mechanism of EC + FLU on oropharyngeal candidiasis (OPC) caused by drug-resistant strains of C. albicans has not been investigated. This study aimed to investigate the protective effect and mechanism of EC combined with FLU against C...

Vulvovaginal candidiasis (VVC) is a fungal infection caused mainly by Candida albicans. The treatment of VVC with azoles has been impaired due to the increased cases of resistance presented by this pathogen. The aim of the present study was to investigate the antifungal activity of mucoadhesive chitosan nanoparticles encapsulating both green propolis and fluconazole for topical use in the treatment of VVC. The nanoparticles were prepared by the ionic gelation method, resulting in a size of 316.5 nm containing 22 mg/kg of green propolis and 2...

Fusarium species represent an opportunistic fungal pathogen in patients with an unrelated disease. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico. The diagnosis of proven fusariosis was made according to European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. Forty-nine cases were identified in our series...

Coccidioidomycosis is a fungal disease in arid regions of the United States that is predicted to expand with climate change. Cases in military personnel and military working dogs (MWDs) impact personnel readiness and result in healthcare costs. To examine Coccidioides exposure among MWDs, 276 banked serum samples were retrieved from dogs housed in California, Texas, Arizona, New Mexico, Nevada, and Utah. Using gel immunodiffusion, six (2.1%) specimens were IgG-positive; three (1.1%) were equivocally IgM-positive...

Aspergillus fumigatus is a fungal species causing diverse diseases in human. The use of azoles for treatments of A. fumigatus diseases has resulted in azole resistance. Azoles are also widely used in the environment for crop protection, which resulted in azole resistance. Resistance is primarily due to mutations in cyp51A, which encodes the target protein for azoles. Here we addressed the occurrence of azole resistance in soils from a vast part of Switzerland. We aimed to associate the use of azoles in the environment with the occurrence of azole resistance...

Candida auris is an emerging fungal pathogen that is feared to spread of infection because of its propensity for multidrug resistance and high mortality rate. This pathogenic yeast is classified into four major clades by phylogenetic analyses, which are referred to the South Asia clade (clade I), East Asia clade (clade II), South Africa clade (clade III), and South America clade (clade IV), based on the location of the initial isolate. In this study, we evaluated the virulence of C. auris strains belonging to four major clades and the therapeutic effects of micafungin in a silkworm infection model...

Cutaneous Coccidioidomycosis (CC) infection can present with a wide variety of clinical presentations and is well known as a 'great imitator'. We performed a retrospective analysis of patients with CC in a large referral center in Central Valley, California, from 2010 to 2022 using the ICD9 and ICD10 codes for coccidioidomycosis and CC. We identified forty patients with CC during the study period. The mean age of the study population was 43 years (with standard deviation of 14.08). Among these, 60% were men and 40% women...

Candidiasis is one of the most important fungal diseases and generally refers to diseases of the skin or mucosal tissues caused by Candida species. Candida glabrata is an opportunistic human fungal pathogen. Infection with C. glabrata has significantly increased due to innate antifungal drug tolerance and the ability to adhere to mucocutaneous surfaces. SAGA complex contains two different post-translational modifications, histone acetylation (HAT module) and deubiquitination (DUB module), which are decisive in gene regulation and highly conserved in eukaryotes...

Dermatophytosis is a superficial cutaneous infection, most commonly caused by fungal species such as Microsporum canis, Nannizzia gypsea (Microsporum gypseum) and Trichophyton mentagrophytes in dogs and cats. The zoonotic potential of these species is concerning, as companion animals are increasingly close to their owners. Therefore, the objectives of the study were to evaluate the current prevalence of Nannizzia causing canine and feline dermatophytosis in Curitiba and Metropolitan Region, as well as perform phenotypic and phylogenetic characterization of these isolates...

The clinical utility of Coccidioides species antifungal susceptibility testing (AST) remains unclear. This study describes the clinical course of 8 patients with severe or chronic coccidioidomycosis and subsequent Coccidioides AST. We present the clinical manifestations, antifungal treatment regimens, and clinical outcomes for these patients.

The incidence of invasive fungal disease (IFD) is on the rise due to increasing numbers of highly immunocompromised patients. Nosocomial IFD remains common despite our better understanding of its risk factors and pathophysiology. High-efficiency particulate air filtration with or without laminar air flow, frequent air exchanges, a positive pressure care environment and environmental hygiene, amongst other measures, have been shown to reduce the mould burden in the patient environment. Environmental monitoring for moulds in areas where high-risk patients are cared for, such as haematopoietic cell transplant units, has been considered an adjunct to other routine environmental precautions...

C. tropicalis, a human conditionally pathogenic yeast, is distributed globally, especially in Asia-Pacific. The increasing morbidity and azoles resistance of C. tropicalis have made clinical treatment difficult. The correlation between clonality and antifungal susceptibility of clinical C. tropicalis isolates has been reported. To study the putative correlation in C. tropicalis isolated from normally sterile body fluid specimens and explore the distinct clonal complex (CC) in Hefei, 256 clinical C. tropicalis isolates were collected from four teaching hospitals during 2016 to 2019, of which 30 were fluconazole-resistant (FR)...

Cryptococcus neoformans is the primary causative agent of cryptococcosis. Since C. neoformans is an environmental pathogen that thrives at temperatures between 25°C and 30°C, it needs to adapt to heat stress in order to cause infection in mammalian hosts. In this study, we aimed to investigate the role of an uncharacterized gene, CNAG_03308. Although the CNAG_03 308 deletion strain grew as well as the parent strain KN99, it produced yeast cells with abnormal morphology at 37°C and failed to propagate at 39°C...