Dimorphic Fungus Research Articles

Update on the Epidemiology, Diagnosis, and Treatment of Coccidioidomycosis.

Coccidioidomycosis is a fungal infection caused by Coccidioides immitis and Coccidioides posadasii. The dimorphic fungi live in the soils of arid and semi-arid regions of the western United States, as well as parts of Mexico, Central America, and South America. Incidence of disease has risen consistently in recent years, and the geographic distribution of Coccidioides spp. appears to be expanding beyond previously known areas of endemicity. Climate factors are predicted to further extend the range of environments suitable for the growth and dispersal of Coccidioides species. Most infections are asymptomatic, though a small proportion result in severe or life-threatening forms of disease. Primary pulmonary coccidioidomycosis is commonly mistaken for community-acquired pneumonia, often leading to inappropriate antibacterial treatment and unnecessary healthcare costs. Diagnosis of coccidioidomycosis is challenging and often relies on clinician suspicion to pursue laboratory testing. Advancements in diagnostic tools and antifungal therapy developments seek to improve the early detection and effective management of infection. This review will highlight recent updates and summarize the current understanding of the epidemiology, diagnosis, and treatment of coccidioidomycosis.

Imaging findings of pulmonary blastomycosis in pediatric patients.

Blastomycosis is caused by Blastomyces dermatitidis, a thermally dimorphic fungus that lives in the form of spores in the soil in North America. The main mode of transmission is through the inhalation of these spores. Despite the importance of knowing the imaging characteristics of blastomycosis given the suggested high rates of dissemination in symptomatic children, a paucity of literature focuses on the imaging patterns of blastomycosis in the pediatric population. In this review, we describe the main imaging findings of pediatric pulmonary blastomycosis and briefly review extrapulmonary manifestations of the disease. Familiarity with these imaging manifestations is important to aid in rapid diagnosis.

Pathogenicity and Growth Conditions Modulate Fonsecaea Extracellular Vesicles' Ability to Interact With Macrophages.

Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous mycosis caused by black, dimorphic, and filamentous fungi of the Herpothrichiellaceae family, such as species of the genus Fonsecaea. These fungi can switch between the saprophytic forms (conidia and hyphae) and the pathogenic form, the muriform cells (MCs), which is considered an essential mechanism for fungal virulence. Nearly all types of cells can produce membranous structures formed by a lipid bilayer that communicate extracellularly with other cells, known as “extracellular vesicles” (EVs), which may act as virulence factors, as observed for several species of pathogenic fungi. Our findings demonstrated for the first time that F. pedrosoi, F. nubica, and F. erecta produce EVs in response to nutritional conditions. The EVs varied in sterol and protein contents, size, and morphology. Moreover, the EVs induced different cytokine and nitric oxide release patterns by bone marrow-derived macrophages (BMDMs). The EVs activated IL-1β production, possibly acting as the first signal in inflammasome activation. Unlike the pathogenic species, the EVs isolated from F. erecta did not significantly stimulate TNF and IL-10 production in general. Overall, these results demonstrated that different species of Fonsecaea produce EVs capable of modulating pro- and anti-inflammatory cytokine and nitric oxide production by BMDMs and that growth conditions affected the immunomodulatory capacities of the EVs as well as their size, content, and morphology.

Clinical and Eco-Epidemiological Aspects of a Novel Hyperendemic Area of Paracoccidioidomycosis in the Tocantins-Araguaia Basin (Northern Brazil), Caused by Paracoccidioides sp.

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Brazil. The disease is caused by dimorphic fungi nested within the Paracoccidioides genus. We described 106 PCM cases (47.1 cases/year) at the Tropical Diseases Public Hospital of Tocantins State. PCM was prevalent in males and rural workers over 50 years; the chronic pulmonary form predominated in 67% of cases. The male-to-female ratio was 2.65:1, with more women affected than other endemic regions of Brazil. Urban or indoor activities were reported in women and are ascribed to disease urbanization. qPCR-based assays confirmed the identification of Paracoccidioides DNA in 37 biological specimens. Paracoccidioides sp. DNA was found in 53% of the environmental samples, suggesting autochthonous infections. Therefore, the Tocantins-Araguaia basin must be considered a novel hyperendemic area of PCM in Brazil, reinforcing the importance of including PCM as a notifiable disease, requiring specific diagnosis and health measures.

Invasive and Subcutaneous Infections Caused by Filamentous Fungi: Report from a Portuguese Multicentric Surveillance Program.

Invasive fungal infections (IFI) have significantly increased over the past years due to advances in medical care for the at-risk immunocompromised population. IFI are often difficult to diagnose and manage, and can be associated with substantial morbidity and mortality. This study aims to contribute to understanding the etiology of invasive and subcutaneous fungal infections, their associated risk factors, and to perceive the outcome of patients who developed invasive disease, raising awareness of these infections at a local level but also in a global context. A laboratory surveillance approach was conducted over a seven-year period and included: (i) cases of invasive and subcutaneous fungal infections caused by filamentous/dimorphic fungi, confirmed by either microscopy or positive culture from sterile samples, (ii) cases diagnosed as probable IFI according to the criteria established by EORTC/MSG when duly substantiated. Fourteen Portuguese laboratories were enrolled. Cases included in this study were classified according to the new consensus definitions of invasive fungal diseases (IFD) published in 2020 as follows: proven IFI (N = 31), subcutaneous fungal infection (N = 23). Those proven deep fungal infections (N = 54) totalized 71.1% of the total cases, whereas 28.9% were classified as probable IFI (N = 22). It was possible to identify the etiological fungal agent in 73 cases (96%). Aspergillus was the most frequent genera detected, but endemic dimorphic fungi represented 14.47% (N = 11) of the total cases. Despite the small number of cases, a high diversity of species were involved in deep fungal infections. This fact has implications for clinical and laboratory diagnosis, and on the therapeutic management of these infections, since different species, even within the same genus, can present diverse patterns of susceptibility to antifungals.

A case of PUO in diabetes mellitus

Histoplasma capsulatum, a thermal dimorphic fungus, is the agent of histoplasmosis. It is a common cause of endemic mycosis. We report the case of a 64-year-old female, a known case of diabetes mellitus, hypertension, beta-thalassemia trait who presented with persistent fever, decreased appetite and weight loss for a period of 1 month and found to have anaemia and hepatosplenomegaly. She was diagnosed with histoplasmosis on liver biopsy. She was started on amphotericin ‘B’ liposomal for 14 days. She showed marked improvement symptomatically and later put on tablet itraconazole 200 mg twice a day for 1 year and was advised for follow-up.

A Langmuir-Blodgett Study of the Interaction between Amphotericin B and Lipids of Histoplasma capsulatum.

Histoplasma capsulatum is a dimorphic, thermal, and nutritional fungus. In the environment and at an average temperature of 28 °C, it develops as a mold that is composed of infecting particles. Once in the host or in cultures at 37 °C, it undergoes a transition into the parasitic form. In the present work, we performed chemical extraction and characterization using chromatography techniques of the associated lipid composition of the external surface of the cell wall of the mycelial phase of two isolates of the H. capsulatum: one clinical and one environmental. Several differences were evidenced in the fatty acids in the phospholipid composition. Surface pressure–area isotherms and compression module curves of the Amphotericin B and lipid extract monolayers, as well as (AmB)-lipid extract mixed monolayers were recorded. Results show a high affinity of AmB towards lipid extracts. The most stable monolayers were formed by AmB + environmental with a mass ratio of 1:3 and AmB + clinical with a mass ratio of 1:2. Knowledge of the AmB aggregation processes at a molecular level and the characterization of the lipid extracts allows the possibility to understand the interaction between the AmB and the lipid fractions of H. capsulatum.

Disseminated Talaromyces marneffei in newly diagnosed HIV patient.

A 31-year-old Chinese man referred to the haematology clinic, was presented with recurrent fever for 19 days and two enlarged lymph nodes on the left neck. Past medical history was unremarkable. Laboratory data revealed white blood cell (WBC) count 9.81 × 109/L (neutrophilic band granulocyte 67%, neutrophilic myelocyte 11%, neutrophilic metamyelocyte 7%, polymorphonuclear neutrophil 6%, lymphocyte 5%, eosinophil 1%, monocyte 2%, basophil 1% and nucleated red blood cell 18/100 WBC), haemoglobin 77 g/L and platelet count 41 × 109/L. The peripheral blood and bone marrow aspirate smear revealed small round-to-ovoid yeast cells located predominantly within or surrounding the neutrophil (top left, middle and right, 1000×, Wright-Giemsa staining). The blood culture showed the fungus grown in a mould form arranged in a mulberry-like pattern and produced a soluble red pigment that diffuses into the sabouraud medium (bottom left). Lactophenol cotton blue staining confirmed numerous yeast-like organisms by the microscopic morphology (bottom middle, 400×). Fungus staining also showed numerous blue yeast-like organisms by fluorescence microscope (bottom right, 400×). The patient was subsequently diagnosed with AIDS having HIV antibody, and the blood cultures showed the growth of Talaromyces marneffei, a dimorphic fungus that is an important opportunistic pathogen. After treatment with anti-fungus and anti-HIV drug, this patient had significantly improved and discharged. The authors would like to thank the encouragement and support of the members who take advanced study in the unit of cytology of the Department of Clinical Laboratory, Zhejiang Provincial People's Hospital. Yanxia Chen was supported by the Zhejiang Provincial Natural Science Fund (No. LY20H100008). Financing entity had no role in the study design, data collection or analysis, decision to publish or preparation of the manuscript. The authors declared that they have no conflict of interest. Zhejiang Provincial Natural Science Fund, Grant Number: LY20H100008. Yingcai Huang provided the haematology picture and wrote the manuscript. Haiyan Cui provided the microbiology picture. Yanxia Chen analysed the data. Jinlin Liu wrote the manuscript. All authors reviewed this manuscript and agreed to submit it. This study was approved by the ethical committee of Longgang District People's Hospital of Shenzhen & The Second Affiliated Hospital of the Chinese University of Hong Kong (No. 2022007). This study did not involve any personal information, but only reports the laboratory data. Therefore, the patient consent was waived, and this waive was approved by the ethical committee of Longgang District People's Hospital of Shenzhen & The Second Affiliated Hospital of the Chinese University of Hong Kong.

Characterization of the Growth and Morphology of a BSL-2 Coccidioides posadasii Strain That Persists in the Parasitic Life Cycle at Ambient CO2.

Coccidioides is a dimorphic fungus responsible for Valley Fever and is the cause of severe morbidity and mortality in the infected population. Although there is some insight into the genes, pathways, and growth media involved in the parasitic to saprophytic growth transition, the exact determinants that govern this switch are largely unknown. In this work, we examined the growth and morphology of a Coccidioides posadasii strain (C. posadasii S/E) that efficiently produces spherules and endospores and persists in the parasitic life cycle at ambient CO2. We demonstrated that C. posadasii S/E remains virulent in an insect infection model. Surprisingly, under spherule-inducing conditions, the C. posadasii S/E culture was found to be completely hyphal. Differential interference contrast (DIC) and transmission electron microscopy (TEM) revealed unexpected cellular changes in this strain including cell wall remodeling and formation of septal pores with Woronin bodies. Our study suggests that the C. posadasii S/E strain is a useful BSL-2 model for studying mechanisms underlying the parasitic to saprophytic growth transition—a morphological switch that can impact the pathogenicity of the organism in the host.

The Role of Isavuconazonium Sulphate for the Treatment of Blastomycosis: A Case Series and Antifungal Susceptibility.

Background Blastomyces spp, the etiologic agents of blastomycosis, are endemic dimorphic fungi that require prolonged antifungal therapy, which can be complicated by adverse drug effects. Isavuconazonium sulphate (ISA) is a triazole with in vitro and in vivo activity against Blastomyces spp, but there is a paucity of clinical data supporting its use for treatment of blastomycosis.MethodsThis retrospective case series identified 14 patients with blastomycosis at least partially treated with ISA at the University of Wisconsin between 2015 and 2019. Treatment duration and outcomes were documented. In addition, 29 clinical isolates of Blastomyces spp between 2004 and 2017 were tested for minimum inhibitory concentrations against ISA and other antifungals.ResultsFourteen patients were treated with a median of 255 days of ISA accounting for 68% of total therapy. Half (7 of 14) of the patients were immunocompromised, 11 of 14 (79%) were proven cases of blastomycosis, 7 of 14 (50%) had central nervous system (CNS) involvement, and 11 of 14 (79%) were cured. Antifungal susceptibility testing showed a consistently low minimum inhibitory concentration to ISA ≤ 0.015 mcg/mL.ConclusionsThis case series supports the efficacy and safety for ISA in the treatment of blastomycosis with or without CNS disseminated, especially when alternative triazoles cannot be used.

A molecular beacon assay for monitoring RNA splicing.

Small molecule targeting of self-splicing RNAs like group I and II introns has been limited in part by the lack of a universal high-throughput screening platform for studies of splicing inhibition and kinetics. Here, we present the development of a molecular beacon assay for monitoring the accumulation of spliced exons during RNA splicing reactions. In this case, we applied it to the autocatalyzed reaction of the H.c.LSU group II intron found in the mitochondria of the pathogenic dimorphic fungus Histoplasma capsulatum. We find that a molecular beacon with the loop length of 18 nucleotides selectively recognizes ligated exons formed during self-splicing and exhibits high fluorescent signal upon binding of its target. We demonstrate that the fluorescent assay using molecular beacons can be successfully applied to kinetic characterization of the splicing reaction and determination of inhibition constants for small molecules. The results presented herein offer support for a molecular beacon approach to identifying small molecule inhibitors of intron splicing.

Late onset endophthalmitis with rare fungus Exophiala dermatitidis

The authors report a case of a 64-year-old diabetic male patient with late-onset fulminant fungal endophthalmitis occurring 6 weeks following complicated cataract surgery. A pigmented, dimorphic fungus known as Exophiala dermatitidis was isolated from aqueous and vitreous samples of the patient. The patient underwent pars plana vitrectomy, followed by daily injections of intravitreal voriconazole, and eventually had marked improvement in the best-corrected visual acuity to 6/9. So far, eight cases of Exophiala endophthalmitis have been reported in the literature, of which six have had a poor visual outcome. This case report demonstrates a successful outcome in a case of E. dermatitidis endophthalmitis, tackled with an aggressive medical and surgical approach.

Progressive disseminated histoplasmosis in HIV-positive patients.

Histoplasmosis is the most common endemic mycosis among people living with advanced HIV infection. Describe general aspects and challenges of this disease and its association with HIV. Review of literature. Articles found using different combinations of terms including "disseminated histoplasmosis" and AIDS/HIV or immunosuppression in PubMed, Scopus, WHO Global health library, and Scielo database. We look for information on epidemiology, pathogenesis, diagnosis, and treatment of histoplasmosis in AIDS patients. Histoplasmosis is caused by Histoplasma capsulatum, a dimorphic fungus encountered throughout the world, mainly in soil enriched with bat and bird excreta. Progressive disseminated histoplasmosis is the main presentation of this mycosis in people living with advanced HIV and is fatal if left untreated. Symptoms include a systemic disease characterized by fever, weight loss, night sweats, skin manifestations, hepatomegaly, splenomegaly, and septic shock. Diagnostic tests include culture, visualization of H. capsulatum by direct and histopathological examination, serology, antigen, molecular, and skin testing. Patients with disseminated disease require aggressive and prolonged treatment to eradicate the pathogen and include amphotericin B and itraconazole. In many low income countries of endemic regions, histoplasmosis in HIV-positive patients is often undiagnosed or misdiagnosed as another opportunistic infection, due to the similarity in clinical manifestations and to the paucity of better diagnostic tests. Histoplasmosis remains a neglected disease. Few studies about the disease and expensive treatments make it difficult to reduce the morbidity and mortality of this condition. Public health services and physicians must be aware of histoplasmosis' burden among the HIV-positive population.

Properties and Effect of Fresh Concentrated Extract of Garlic on Different Bacteria and Fungi

Aims: Study some characteristics of fresh concentrated extract of garlic (FCEG) and analyze its effect on the growth of different bacteria and fungi.
 Place and Duration of Study: Sample: Faculty of Chemical Sciences. Autonomous University of San Luís Potosí, S.L.P., between march and November 2020.
 Methodology: To obtain the FCEG, 15 heads of raw garlic, previously peeled, were ground in a mortar and the suspension obtained was filtered through gauze, pressing to obtain a greater amount of filtrate, and kept covered at 4oC. For the study of some of their characteristics, the yeast Candida albicans was used. Petri dishes containing Sabouraud dextrose agar were inoculated with 1 x 106 yeasts/mL and 50 µL of FCEG, and were incubated at 28oC for 5 days, comparing growth with respect to a control without FCEG (all inhibition experiments described below were performed with the same protocol), while for the study of antifungal properties analyzed the effect of the extract on different strains of bacteria, yeasts, and fungi.
 Results: Some of the factors that modify antifungal activity of FCEG are dilution, incubation temperature, protein concentration, half-life, capping and uncapping of tubes, and treatment with activated carbon. Regarding the growth inhibition analyses, it was found that all the species analyzed were susceptible to FCEG, among which the following stand out: the the dimorphic fungus Histoplasma capsulatum, causing systemic mycoses, the yeasts Cryptococcus neoformans and C. albicans, as well as different species of Dermatophytes, Aspergillus, and bacteria.
 Conclusion: FCEG shows a good antimicrobial effect against a wide variety of bacteria, yeast, and fungal species, which makes its application in medical therapy and agriculture, as well as being cheap, easy to obtain and does not cause side effects, although more studies are required for its therapeutic application.

Clinical and Epidemiological Characteristics of Sporotrichosis in a Reference Center of Uruguay.

Background: Sporotrichosis is a fungal implantation disease of subacute/ chronic course caused by species of the dimorphic fungus Sporothrix spp. This infection usually develops after traumatic inoculation of contaminated soil, plants or organic material contaminated by Sporothrix spp. conidia into skin or mucosa. The objective of this work is to contribute to the knowledge of sporotrichosis in Uruguay by providing a report of a series of cases diagnosed in a reference center. Methods: We conducted a retrospective, observational, descriptive and cross-sectional study of cases of sporotrichosis diagnosed in the last 38 years. Results: In the period analyzed, 157 cases of sporotrichosis were diagnosed, 152 of those corresponded to male patients. The most frequent clinical presentation was nodular lymphatic in 120 patients. In relation to epidemiological antecedents, 128 patients had been scratched by armadillos during hunting. Conclusions: Sporotrichosis in Uruguay is a sporadic disease with a clear seasonal pattern related to particular social practices, such as hunting armadillos. Related to this practice, the affectation is greater in males and in young adults.

Considerations about the Geographic Distribution of Histoplasma Species.

Histoplasmosis is a mycotic infection principally affecting pulmonary tissue; sometimes, histoplasmosis can progress into a systemic disease. This infection involves immunocompetent and immunosuppressed human and other mammalian hosts, depending on particular circumstances. Histoplasmosis infection has been documented worldwide. The infection is acquired by inhaling infective mycelial propagules of the dimorphic fungus Histoplasma capsulatum. New reports of clinical cases of histoplasmosis in extreme latitudes could be related to human social adaptations and climate changes in the world, which are creating new favorable environments for this fungus and for bats, its major natural reservoirs and dispersers. Histoplasma has been isolated from most continents, and it is considered a complex of cryptic species, consisting of various groups of isolates that differ genetically and correlate with a particular geographic distribution. Based on updated studies, Histoplasma taxonomy is adjusting to new genetic data. Here, we have suggested that Histoplasma has at least 14 phylogenetic species distributed worldwide and new genotypes that could be under deliberation. Histoplasma's geographic radiation began in South America millions of years ago when the continents were joined and the climate was favorable. For fungal spreading, the role of bats and some birds is crucial, although other natural factors could also participate.

A rare presentation of blastomycosis as a multi-focal infection involving the spine, pleura, lungs, and psoas muscles in a Saudi male patient: a case report

BackgroundBlastomycosis is a disease caused by the fungus Blastomyces—a thermally dimorphic fungus that can cause granulomatous and/or purulent infection.Case presentationWe report here a case of chronic blastomycosis infection in a 24-year-old male patient from Saudi Arabia who presented with recurrent skin abscesses associated with deep-seated and multilevel paraspinal (dorsal and lumbar) collections and bilateral empyema with pulmonary involvement and bilateral psoas abscesses. The diagnosis was made after a CT-guided pleural biopsy revealed the characteristic histopathological findings of blastomycosis. The patient underwent several drainage procedures and was successfully treated with a long-term course of oral itraconazole.ConclusionsChronic blastomycosis may have clinical and radiologic features similar to thoracic tuberculosis or malignant disease. There is no definite clinical symptom of blastomycosis, and thus a high degree of suspicion is required for early diagnosis. This case is a rare form of blastomycosis with chronic multifocal purulent infection and is the second case of blastomycosis reported in Saudi Arabia.

Key thermally dimorphic fungal pathogens: shaping host immunity.

Exposure to fungal pathogens from the environment is inevitable and with the number of at-risk populations increasing, the prevalence of invasive fungal infection is on the rise. An interesting group of fungal organisms known as thermally dimorphic fungi predominantly infects immunocompromised individuals. These potential pathogens are intriguing in that they survive in the environment in one form, mycelial phase, but when entering the host, they are triggered by the change in temperature to switch to a new pathogenic form. Considering the growing prevalence of infection and the need for improved diagnostic and treatment approaches, studies identifying key components of fungal recognition and the innate immune response to these pathogens will significantly contribute to our understanding of disease progression. This review focuses on key endemic dimorphic fungal pathogens that significantly contribute to disease, including Histoplasma, Coccidioides and Talaromyces species. We briefly describe their prevalence, route of infection and clinical presentation. Importantly, we have reviewed the major fungal cell wall components of these dimorphic fungi, the host pattern recognition receptors responsible for recognition and important innate immune responses supporting adaptive immunity and fungal clearance or the failure thereof.

Study of Dimorphism Transition Mechanism of Tremella fuciformis Based on Comparative Proteomics.

Tremella fuciformis is a dimorphic fungus that can undertake a reversible transition between yeast-like conidia and hyphal forms. The transformation mechanism and proteomic differences between these two forms have not been reported. Therefore, in this study, we attempted to explore the differential protein profiles of dikaryotic yeast-like conidia from fruiting bodies and mycelia (FBMds) and dikaryotic mycelia (DM) by synthetically applying high-resolution MS1-based quantitative data-independent acquisition (HRMS1-DIA) full proteomics and parallel reaction monitoring (PRM) targeted proteomics. The results showed that a total of 5687 proteins were quantified, and 2220 of them (39.01%) showed more than a two-fold change in expression. The functional analysis of the differentially expressed proteins (DEPs) confirmed that the DEPs were mainly located in the membrane and nucleus. The FBMds tended to express proteins involved in biosynthesis, metabolism, DNA replication and transcription, and DNA damage repair. At the same time, DM exhibited an increased expression of proteins involved in signal transduction mechanisms such as the mitogen-activated protein kinase (MAPK) signaling pathway and the Ras signaling pathway. Further, phosphorylation analysis confirmed the importance of the MAPK signaling pathway in T. fuciformis dimorphism, and comparative metabolism analysis demonstrated the metabolic difference between FBMds and DM. The information obtained in the present study will provide new insights into the difference between FBMds and DM and lay a foundation for further research on the dimorphism formation mechanism of T. fuciformis.

Humidity and low pH boost occurrence of Onygenales fungi in soil at global scale

Soils are important reservoirs for potential human pathogens and opportunistic fungi such as the dermatophyte or dimorphic fungi in the order Onygenales. In soils, these taxa are decomposers but many of them have the potential to cause respiratory and skin diseases in humans and, in some cases, systemic infections. Even so, the factors that determine the biogeography and ecology of order Onygenales remain largely undocumented. To address this knowledge gap, we surveyed members of Onygenales from topsoil fungal communities at 235 sites across six continents and provided a first global atlas. We retrieved 4.3% of the total fungal sequences (∼420 Onygenales) across nine biomes ranging from deserts to tropical forests. This work advances our knowledge on the ecology and global distribution of order Onygenales and suggests the hypothesis that wet and acid soils support the larger proportions of these fungi, while their richness is constrained by aridity.