Fungal Organisms Research Articles

Nasal trichosporonosis in 2 mixed-breed ewes.

Two adult mixed-breed ewes were presented with a 2-wk history of upper respiratory disease. Both animals were depressed, with bilateral serosanguineous nasal discharge and harsh bronchovesicular sounds accompanied by crackles and wheezes on auscultation. One animal was recumbent and was euthanized at presentation. The other animal with similar signs, as well as exophthalmos, was euthanized because of a mass in the nasal passages. On autopsy, severe pyogranulomatous and necrotizing ethmoidal rhinitis with focal pyogranulomatous pneumonia was diagnosed in both animals. An intralesional fungal organism was identified in the nares and lungs of both animals. The organism could not be isolated via fungal culture but was identified as Trichosporon sp. by a PCR assay. Trichosporon spp. are rarely associated with disease in veterinary medicine. This ubiquitous fungus might cause disease following trauma to the nasal passages or secondary to immunocompromise.

Mortality Caused by Candida auris Bloodstream Infections in Comparison with Other Candida Species, a Multicentre Retrospective Cohort.

Candida auris is an emerging pathogen considered to be critical in the World Health Organization fungal organisms list. The study aims to determine the mortality and hospital stays attributed to Candida auris (C. auris) compared to other Candida species in adult patients with candidemia. A retrospective cohort of adults with candidemia was examined from seven centres in Colombia between 2016 and 2021. The primary outcome was 30-day mortality, and the secondary outcome was the length of hospital stay among survivors. Adjustment of the confounding variables was performed using inverse probability weights of exposure propensity score (candidemia by C. auris), survival regression models (Weibull distribution), and a counting model (negative binomial distribution). A value of 244 (47.6%) of the 512 patients with candidemia died within the first 30 days. The crude mortality in C. auris was 38.1% vs. 51.1% in Candida non-auris (CNA). In the Weibull model, mortality in the C. auris group was lower (adjusted HR: aHR- 0.69, 95% CI: 0.53-0.90). Antifungal treatment also decreased mortality, with an aHR of 0.36 (95% CI 0.27-0.47), while the presence of septic shock on patient progression increased it, with an aHR of 1.73 (95% CI 1.41-2.13). Among the patients who survived, no differences in the length of hospital stay were observed between the C. auris and the CNA groups, with an incidence rate ratio of 0.92 (95% CI: 0.68-1.22). Mortality in patients with C. auris bloodstream infections appears lower when adjusted for numerous confounding variables regarding treatment and the presence of septic shock in patient progression. We identified no significant effect of C. auris on the length of hospital stay in surviving patients.

Pituitary abscess: a case report and systematic review of 488 cases

BackgroundPituitary abscess (PA) is a rare condition and not well understood. We aimed to describe a case and perform a comprehensive systematic review to explore presenting symptoms, radiological findings, endocrine abnormalities and mortality.AimTo identify presenting symptoms, radiological findings, endocrinological abnormalities and predictors of mortality for PA.MethodsWe systematically reviewed the literature to identify all case reports of PA. Data regarding presentation, mortality, radiological findings, endocrinological abnormalities and treatment was extracted.ResultsWe identified 488 patients from 218 articles meeting the inclusion criteria. Mortality was 5.1%, with days to presentation (OR 1.0005, 95% CI 1.0001–1.0008, p < 0.01) being the only identified independent predictor of mortality. Mortality rates have decreased over time, with cases published prior to 2000 having higher mortality rates (OR 6.92, 95% CI 2.80–17.90, p < 0.001). The most common symptom was headache (76.2%), followed by visual field defects (47.3%). Classical signs of infection were only present in 43%. The most common imaging feature on magnetic resonance imaging (MRI) was high T2 and low T1 signal of the pituitary gland with peripheral contrast enhancement. Over half (54.8%) were culture negative, with the most common bacterial organism being staphylococcus aureus (7.8%) and fungal organism being aspergillus (8.8%). The most common endocrine abnormality was hypopituitarism (41.1%), followed by diabetes insipidus (24.8%). Whilst symptoms resolved in most patients, persistent endocrine abnormalities were present in over half of patients (61.0%).ConclusionPA is associated with significant mortality, with delayed presentation increasing risk of mortality. Ongoing endocrinological abnormalities are common. Given the non-specific clinical presentation, the appearance of high T2, low T1 and peripheral contrast enhancement of the pituitary on MRI should prompt consideration of this rare disease.

Organism type of infection is associated with prognosis in sepsis: an analysis from the MIMIC-IV database

BackgroundSepsis has a high mortality rate, which is expensive to treat, and is a major drain on healthcare resources; it seriously impacts the quality of human life. The clinical features of positive or non-positive blood cultures have been reported, but the clinical features of sepsis with different microbial infections and how they contribute to clinical outcomes have not been adequately described.MethodsWe extracted clinical data of septic patients with a single pathogen from the online Medical Information Mart for Intensive Care(MIMIC)-IV database. Based on microbial cultures, patients were classified into Gram-negative, Gram-positive, and fungal groups. Then, we analyzed the clinical characteristics of sepsis patients with Gram-negative, Gram-positive, and fungal infections. The primary outcome was 28-day mortality. The secondary outcomes were in-hospital mortality, the length of hospital stay, the length of ICU stay, and the ventilation duration. In addition, Kaplan–Meier analysis was used for the 28-day cumulative survival rate of patients with sepsis. Finally, we performed further univariate and multivariate regression analyses for 28-day mortality and created a nomogram for predicting 28-day mortality.ResultsThe analysis showed that bloodstream infections showed a statistically significant difference in survival between Gram-positive and fungal organisms; drug resistance only reached statistical significance for Gram-positive bacteria. Through univariate and multivariate analysis, it was found that both the Gram-negative bacteria and fungi were independent risk factors for the short-term prognosis of sepsis patients. The multivariate regression model showed good discrimination, with a C-index of 0.788. We developed and validated a nomogram for the individualized prediction of 28-day mortality in patients with sepsis. Application of the nomogram still gave good calibration.ConclusionsOrganism type of infection is associated with mortality of sepsis, and early identification of the microbiological type of a patient with sepsis will provide an understanding of the patient's condition and guide treatment.

P21 Facial papules in an immunocompromised patient

Abstract A 29-year-old man presented with a 6-week history of clustered facial papules. Of note, he had a diagnosis of HIV 5 months previously and was on maintenance antiretroviral treatment. His initial CD4 count was 5, which increased to 38, and his viral load was now no longer detectable. He had also been treated for cytomegalovirus reactivation, pneumocystis pneumonia and suspected mycobacterium infection for the previous 3 months. He had ongoing symptoms of malaise, fevers, weight loss and nausea, along with abnormal liver function tests and a raised C-reactive protein. A bone marrow trephine showed noncaseating discrete small granulomas; Grocott and periodic acid–Schiff (PAS) stains were negative. Prior to his dermatology review, the papules were initially perioral and he had been treated with empiric valaciclovir for suspected herpes simplex virus (HSV) but with no resolution. Testing for HSV DNA and syphilis was negative. On examination, there were clusters of small nontender, well-circumscribed papules (some umbilicated), distributed on the forehead, cheeks, and cutaneous and mucosal lips. A diagnostic punch biopsy was taken of one of the characteristic papules. Histological examination demonstrated a dense dermal infiltrate of histiocytes with focal non-necrotizing granuloma formation. Interspersed neutrophilic microabscesses and occasional eosinophils were present. PAS stain for fungi confirmed the presence of numerous thick-walled spherules, many with a single distinct nucleus, with some showing binucleation, consistent with fungal organisms located within the histiocytes in the dermis. Differential diagnosis included histoplasmosis, cryptococcosis, blastomycosis and coccidiomycosis. He was commenced on intravenous liposomal amphotericin B for disseminated endemic mycosis while awaiting definitive diagnosis. Formal identification by panfungal polymerase chain reaction of skin tissue was positive for Histoplasma capsulatum and itraconazole was added. The diagnosis was consistent with disseminated histoplasmosis with cutaneous involvement. The lesions resolved completely over 4 weeks, with some residual hyperpigmentation remaining. Histoplasma capsulatum is a dimorphic fungus found in soil and the droppings of bats and birds. Infection is through spore inhalation, with most patients being asymptomatic. It is more prevalent in temperate and tropical climates. Disseminated histoplasmosis occurs mostly in immunocompromised individuals and can be fatal if left untreated. Although endemic to specific world regions, disseminated histoplasmosis should be considered in immunocompromised patients presenting with atypical cutaneous findings, even in regions of low prevalence.

Post-harvest Survey of Fungal Diseases Associated with Soursop (Annona muricata L.) Fruits

Annona muricata L. (soursop) fruit, consumed globally, is highly susceptible to attack by fungal organisms. Fungal fruit rots' impact on Annona muricata is gradually increasing globally, with distribution in tropical areas, including southern Nigeria, resulting in reducing market availability and fruit quality. This study was aimed at surveying the post-harvest disease symptoms associated with Annona muricata fruits displayed for sales and the disease incidence-severity, which indicates the extent of the damage caused by the symptoms. Soursop fruit samples in Port Harcourt Local Government Area (PHALGA) and Obio-Apkor Local Government Area in Rivers State, Nigeria, were surveyed. Each fruit was scored on a disease severity scale of 0–4 (0% no disease), (1–25% trace of disease), (25–50% light disease), (50–75% moderate disease) and (75–100% severe disease). The data obtained were subjected to Analysis of Variance (ANOVA) and Duncan’s Multiple Range Test (DMRT) at 5% level of probability using LSD (Least Significant Difference). The study revealed that Annona muricata fruits were dominated by fungal disease symptoms of dry rot, soft rot, anthracnose, powdery mildew and diplodia fruit rot. There was no significant difference between location pairs for all disease symptoms of incidence and severity of Annona muricata, respectively. Fungal diseases at the post-harvest stage pose a threat to storage durability, distribution and market availability of fruits.

Periprosthetic joint infection:A South African perspective.

South African data on the bacteriology and sensitivity profile of periprosthetic joint infection is lacking. Current regimens for systemic and local antibiotic therapy are based on international literature. These regimens are different for the United States of America and Europe and might thus not be relevant to South Africa. To determine the characteristics of periprosthetic joint infection in a South African clinical setting by identifying the most common organisms cultured and establishing their antibiotic sensitivities in order to propose the most appropriate empiric antibiotic treatment regimen. In the case of two-stage revision procedures, we aim to compare the organisms cultured during the first stage versus organisms cultured during the second stage in second-stage procedures that had positive cultures. Furthermore, in these culture-positive second-stage procedures we aim to correlate the bacterial culture with the erythrocyte sedimentation rate/ C-reactive protein result. We performed a retrospective cross-sectional study looking at all hip and knee periprosthetic joint infections in patients 18 years and older, treated at a government institution and a private revision practice in Johannesburg, South Africa between January 2015 and March 2020. Data were collected from the Charlotte Maxeke Johannesburg Academic Hospital hip and knee and the Johannesburg Orthopaedic hip and knee databanks. We included 69 patients whom underwent 101procedures relating to periprosthetic joint infection. Positive cultures were found in 63 samples, 81 different organisms were identified. The most common organisms cultured were Staphylococcus aureus (n = 16, 19.8%) and Coagulase negative Staphylococcus (n = 16, 19.8%), followed by Streptococci species (n = 11, 13.6%). The positive yield in our cohort was 62.4% (n = 63). A polymicrobial growth was found in 19% (n = 12) of the culture positive specimens. Of all the microorganisms cultured, 59.2% (n = 48) were Gram-positive versus 35.8% (n = 29) Gram-negative. The remainder were fungal and anaerobic organisms at 2.5% (n = 2) each. Gram-positive cultures displayed 100% sensitivity to Vancomycin and Linezolid, whereas Gram-negative organisms displayed 82% sensitivity towards Gentamycin and 89% sensitivity towards Meropenem respectively. Our study identifies the bacteriology of periprosthetic joint infections and their sensitivities in a South African setting. We recommend that empiric antibiotic-loaded cement spacers and systemic antibiotic regimens should consist of Meropenem or Gentamycin; Vancomycin and Rifampicin to achieve the broadest spectrum of coverage and most likely success in eradicating infection.

Fungal indoor Air Quality and Associated Factors in Prison Inmate Cells of East Hararghe Zone and Harari Regional State, Eastern Ethiopia, 2020

The presence of fungi inside of buildings and structures is referred to as fungal indoor air quality. Infections, fragments of fungal cells, and metabolites of fungal organisms can all provide significant challenges in indoor structures, including prison inmate cells. In East Hararghe and Harari regional state, there is no evidence of a fungal load or associated factors in prisons. The purpose of this study was to evaluate the fungal indoor air quality and related factors in prison inmate cells. An Institution based cross-sectional study was conducted. The source and study population were all prisoner cells located in the East Hararghe zone and Harari regional state prisons. 62 prisoner cells were used in the investigation. The approach of non-random sampling was applied. Passively settle able plates were used to collect the samples (Koch sedimentation method). ANOVA, correlation, and chi-square statistical tests were used to examine the row data using SPSS statistical software and Microsoft Excel. The fungal concentrations were highest at 8:00 pm (537 CFU/m³) and lowest at 2:00 pm (115 CFU/m³), respectively. The number of people was poorly connected with the fungal load (r=0.192 and p=0.039), and there was a significant positive weak correlation between the fungal load and temperature (r= 0.275, P=0.031). In contrast, a significant positive correlation between the fungal load and relative humidity in prisoner cells was discovered (r = 0.983; p = 0.004). In conclusion, the fungal concentrations were in the intermediate region (<500CFU/m³) except in one inmate cell of the investigated prisons. This study indicates that, it may pose threats to inmates. As a result, both the Harari region and the eastern Haragie zone prison offices should take action to address the issue. The prison facility needs to be restructured in accordance with current requirements.

Melanonychia and subungual papule in a middle-aged man

Melanonychia and subungual papule in a middle-aged man

MoCbp7, a Novel Calcineurin B Subunit-Binding Protein, Is Involved in the Calcium Signaling Pathway and Regulates Fungal Development, Virulence, and ER Homeostasis in Magnaporthe oryzae.

Calcineurin, a key regulator of the calcium signaling pathway, is involved in calcium signal transduction and calcium ion homeostasis. Magnaporthe oryzae is a devastating filamentous phytopathogenic fungus in rice, yet little is known about the function of the calcium signaling system. Here, we identified a novel calcineurin regulatory-subunit-binding protein, MoCbp7, which is highly conserved in filamentous fungi and was found to localize in the cytoplasm. Phenotypic analysis of the MoCBP7 gene deletion mutant (ΔMocbp7) showed that MoCbp7 influenced the growth, conidiation, appressorium formation, invasive growth, and virulence of M. oryzae. Some calcium-signaling-related genes, such as YVC1, VCX1, and RCN1, are expressed in a calcineurin/MoCbp7-dependent manner. Furthermore, MoCbp7 synergizes with calcineurin to regulate endoplasmic reticulum homeostasis. Our research indicated that M. oryzae may have evolved a new calcium signaling regulatory network to adapt to its environment compared to the fungal model organism Saccharomyces cerevisiae.

A Disease-Specific Antibiogram to Evaluate Empiric Coverage Patterns in Fournier’s Gangrene

To analyze our local antibiogram and antibiotic resistance patterns given concern for multidrug-resistant and fungal organisms in contemporary series detailing causative organisms in Fournier's Gangrene (FG). All patients from 2018 to 2022 were identified from the institutional FG registry. Microorganisms and sensitivities were collected from operative tissue cultures. The primary outcome of this study was the adequacy of our empiric. Secondary outcomes included the rate of bacteremia, the concordance of blood cultures and tissue cultures, and the rate of fungal tissue infections. Escherichia coli and Streptococcus anginosus were most common, identified in 12 patients each (20.0%). Enterococcus faecalis (9, 15.0%), S agalactiae (8, 13.3%) and mixed cultures without a predominant organism (9, 15.0%) were also common. A fungal organism was identified in 9 (15.0%) patients. Patients who were started on Infectious Diseases Society of America guideline adherent antibiotic regimen were not significantly different in terms of bacteremia rate (P=.86), mortality (P=.25), length of stay (P=.27), or final antibiotic duration (P=.43) when compared to those on alternative regimens. Patients with a tissue culture positive for a fungal organism were not significantly different in terms of Fournier's Gangrene Severity Index (P=.25) or length of stay (P=.19). Local disease-specific antibiograms can be a powerful tool to guide empiric antibiotic therapy in FG. Although fungal infections are responsible for a majority of the gaps in empiric antimicrobial coverage at our institution they were present in only 15% of patients and their effect on outcomes does not justify addition of empiric antifungal agents.

Influence of organic matter management on the activity and structure of soil microbial community in intensive tomato (Solanum lycopersicum L.) greenhouse farming

Aim of study: Intensive agriculture impacts physical, chemical, and biological characteristics of soil; therefore, the addition of organic matter (OM) to soil can have significant implications for crop production. This study investigated the impact of three crop management systems on tomato production and soil microbial communities in intensive greenhouse farming. Area of study: Province of Almería (Spain). Material and methods: The three crop management systems included: (1) conventional management, using synthetic chemical fertilizers without OM application (CM); (2) conventional management, using synthetic chemical fertilizers with at least one OM application in the last three years (CMOM); and (3) fully organic management, featuring yearly OM applications and no use of synthetic chemical fertilizers (ORG). Main results: Compared to CM soils, OM addition in CMOM and ORG led to higher soil NO3- and NH4+ content, which in turn increased nitrogen (N) availability, leading to an increase in soil respiration. The addition of OM also altered the composition of prokaryotic and fungal soil communities. Besides, the addition of OM reduced the presence and abundance of potential fungal pathogenic organisms, like Sclerotinia sp. and Plectosphaerella cucumerina. OM addition to conventionally managed greenhouses (CMOM) led to higher crop yields compared to CM greenhouses, resulting in an overall increase of 880 g m-2. Production under fully organic management (ORG) was lowest, possibly due to the nutrient and pest management practices used. Research highlights: Our data show the importance of organic matter management in shaping microbial communities in intensive greenhouse systems, which can be a key factor in developing a more sustainable agriculture to feed a growing human population.

Disseminated Rasamsonia argillacea infection in a dog

ABSTRACT Case history A 4-year-old, male neutered Borzoi presented for unlocalised pain and frequent episodes of vocalisation. Clinical findings Pain was localised to the lumbar spine and radiographs revealed a L3–L4 lesion consistent with discospondylitis. The dog was treated for presumptive bacterial discospondylitis with surgical debridement, spinal stabilisation, and cephalexin. Samples collected from the affected intervertebral disc at the time of surgery revealed lymphoplasmacytic inflammation with no causative agent identified on histopathology or bacterial culture. After an initial period of improvement, signs recurred despite an 8-week antibiotic course, with the development of inappetence, weight loss, polydipsia, and polyuria. Repeat radiographs revealed a new cervical intervertebral lesion, and concurrent pyelonephritis was diagnosed based on blood and urine results. Fungal culture of urine resulted in growth of Rasamsonia argillacea species complex and disseminated fungal disease was clinically diagnosed. Antifungal treatment was commenced, however the dog deteriorated, and euthanasia was performed. Pathological findings Multifocal white plaques were grossly visualised in the spleen, mesenteric lymph nodes, cervical vertebrae, and kidneys. Periodic acid-Schiff-positive, fine, parallel-walled, occasionally branching, septate hyphae 5–10 μm in diameter, and conidia 5–7 μm in diameter were found on sectioning all organs. R. argillacea species complex was identified by fungal culture of urine and was considered the species of fungal organism seen histologically. The isolate was subsequently confirmed as R. argillacea by DNA sequencing. Diagnosis Disseminated Rasamsonia argillacea infection. Clinical relevance Rasamsonia argillacea species complex is a recognised invasive mycosis in veterinary medicine, with disseminated disease causing significant clinical complications and death. This is believed to be the first report of infection caused by R. argillacea in a dog in Australasia and highlights the importance of awareness of a potential fungal aetiology in dogs with discospondylitis. Abbreviations: CLSI: Clinical and Laboratory Standards Institute; CRI: Constant rate infusion; MEC: Minimum effective concentration; MIC: Minimum inhibitory concentration; PAS: Periodic acid-Schiff

705 Evaluation of Invasive Fungal Infections in the Burn ICU

Abstract Introduction Fungal infections are increasingly associated with critical illness, especially in major burn injury. The risk factors of invasive fungal infections include central venous catheter (CVC) placement, mechanical ventilation, broad-spectrum antibiotics, renal replacement therapy (RRT), and total parental nutrition. Critically ill burn patients have additional risk factors including extensive wounds, impaired immune system, and repeated surgical intervention. Despite significant morbidity and mortality caused by invasive fungal infections, efforts to prevent them with antifungal prophylaxis have not improved outcomes. In patients who develop invasive fungal infection, appropriate empiric antifungal therapy is imperative to reduce morbidity and mortality especially in the setting of delayed culture and sensitivity data. The purpose of this study was to characterize risk factors associated with the development of invasive fungal infection, invasive fungal infection organisms and surgical and pharmacological management. Methods A retrospective chart review was completed of adult patients admitted to the burn ICU found to have an invasive fungal infection (defined as at least one positive blood or tissue fungal infection and receipt of systemic antifungal therapy). The primary outcome was to identify common fungal organisms. Secondary outcomes included susceptibility pattern of the organism, location of infection, surgical management including debridement and amputation, pharmacological management, median ICU and hospital length of stay, and in hospital mortality. Results A total of 10 patients of a goal of 100 patients with a median 54% TBSA burns were evaluated at this time. The most common yeast species included candida albicans; mold species included a variety of organisms such as fusarium, zygomycete and paecilomyces. Common risk factors among these patients included CVC access (57%), mechanical ventilation (43%), and RRT (43%). Yeast infections were primarily treated with anidulafungin and fluconazole, while mold infections were managed with systemic amphotericin as backbone in addition to voriconazole or isavuconazole. Patients underwent aggressive surgical debridement for source control. Median ICU stay was 53 days with a median hospital stay of 63 days, and 42% mortality. Conclusions Fungal infections among critically ill burn patients are associated with the high morbidity and mortality rates. Therefore, mitigation of modifiable risk factors is of utmost importance. This retrospective review of common fungal growth in our unit will inform future empiric antifungal management for patients with concern of invasive fungal infections. Applicability of Research to Practice Fungal infections present a clinical challenge for burn practitioners, especially in geographically moist areas. Prevention and informed surgical and pharmacological management are key to overcoming this infectious disease threat.

Candida albicans cholecystitis in a dog with diabetes mellitus

AbstractA 10‐year‐old, 8.9‐kg, spayed, female Jack Russell Terrier, with previously well‐controlled diabetes mellitus, presented with hyporexia of 2‐day duration. Cranial abdominal pain and weight loss were detected on clinical examination. Blood tests, urinalysis, urine protein:creatinine ratio, blood pressure, abdominal ultrasound and liver aspirate cytology revealed hyperglycaemia, elevated serum liver enzyme activities, glucosuria, proteinuria, hypertension, rounded liver edges, irregular hyperechoic gall bladder wall thickening, irregular hyperechoic gall bladder content and vacuolar hepatopathy. Bile cytological examination demonstrated fungal organisms, which were identified as Candida albicans on bile fungal culture. No bacteria were detected on bile cytological examination or bile bacterial aerobic and anaerobic culture. The dog was diagnosed with Candida albicans cholecystitis and recovered after a 12‐week course of oral ketoconazole. This case report highlights the value of performing bile cytology in suspect canine cholecystitis cases and is the first to describe Candida albicans fungal cholecystitis without bacterial coinfection in dogs.

Treatment Outcomes of Fungal Periprosthetic Joint Infection

BackgroundPeriprosthetic joint infection (PJI) continues to challenge surgeons and patients. The burden of fungal organisms may represent approximately 1% of all PJI. Additionally, fungal PJI is difficult to treat. Most available case series are small and report poor success rates. Fungi are opportunistic pathogens and patients who have fungal PJI are believed to be immunocompromised. Additionally, fungal biofilms are more complex than those formed by other pathogens and confer additional drug resistance. Due to these factors, treatment failure is common. MethodsA retrospective review of our institutional registry was performed to identify patients treated for fungal PJI. There were 49 patients identified with 8 excluded for not having follow-up, which left 22 knees and 19 hips for analyses. Demographics, clinical characteristics, and surgical details were collected. The primary outcome was failure defined as reoperation for infection following the index surgery for fungal PJI within 1 year of the index surgery. ResultsFailure occurred in 10 of 19 knees and 11 of the 22 hips. A higher proportion of patients who have extremity grade C failed treatment, and every patient who failed was host grade 2 or 3. The average number of prior surgeries and time from resection to reimplantation were similar between groups. ConclusionTo our knowledge, this represents the largest cohort of fungal PJIs reported in the literature to date. This data supports other literature in that failure rates were high. More study is needed to further understand this entity and improve care for these patients.

Viroid-like RNA-dependent RNA polymerase-encoding ambiviruses are abundant in complex fungi.

Ambiviruses are hybrid infectious elements encoding the hallmark gene of RNA viruses, the RNA-dependent RNA polymerase, and self-cleaving RNA ribozymes found in many viroids. Ambiviruses are thought to be pathogens of fungi, although the majority of reported genomes have been identified in metatranscriptomes. Here, we present a comprehensive screen for ambiviruses in more than 46,500 fungal transcriptomes from the Sequence Read Archive (SRA). Our data-driven virus discovery approach identified more than 2,500 ambiviral sequences across the kingdom Fungi with a striking expansion in members of the phylum Basidiomycota representing the most complex fungal organisms. Our study unveils a large diversity of unknown ambiviruses with as little as 27% protein sequence identity to known members and sheds new light on the evolution of this distinct class of infectious agents with RNA genomes. No evidence for the presence of ambiviruses in human microbiomes was obtained from a comprehensive screen of respective metatranscriptomes available in the SRA.

Bioactivity and quantum chemical calculations оf a new coumarine derivative as a strong antioxidant, antimicrobial and anti-cancer substance

4-(((4-Ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-7-methyl-coumarin was synthesized, and its characterization was done with quantum chemical calculations and spectral techniques. The density functional method (B3LYP) with the 6-311G(d,p) basis set was used to calculate the molecular geometry, vibrational frequencies, and gauge, including atomic orbital (GIAO) 1H and 13C-NMR chemical shift values of the title compound in the ground state. The theoretical vibrational frequencies and chemical shift values agree well with the experimental results. DFT calculations of the density of states (DOS) and frontier molecular orbitals of the title compound were carried out at the B3LYP/6-311G(d,p) level of theory. In the present study, biological activities and molecular docking studies of this triazole ring containing coumarin derivative compound were carried out. Interactions with important residues in active sites were detected in molecular docking studies. In addition, in vitro analysis has shown that anti-microorganism activity is especially effective against bacterial organisms such as E. coli, S. aureus, B. cereus, and fungal organisms such as C. albicans, C. tropicalis. Also, the antioxidant capacity of the test compound was investigated by oxidative stress index (OSI) and radical scavenging power (DPPH.), and its antioxidant potential was found. In addition, it was determined by in vitro anticancer and SDS-PAGE analysis that the test compound does not cause a detrimental cytotoxic effect on healthy cell cultures such as HUVEC and has the potential for anticarcinogenic activity on MCF-7 and MKN-45 cancerous cell cultures.

Investigating the role of Candida albicans as a universal substrate for oral bacteria using a transcriptomic approach: implications for interkingdom biofilm control?

Candida albicans is frequently identified as a colonizer of the oral cavity in health and has recently been termed a "keystone" commensal due to its role on the bacterial communities. However, the role that C. albicans plays in such interactions is not fully understood. Therefore, this study aimed to identify the relationship between C. albicans and bacteria associated with oral symbiosis and dysbiosis. To do this, we evaluated the ability of C. albicans to support the growth of the aerobic commensal Streptococcus gordonii and the anaerobic pathogens Fusobacterium nucleatum and Porphyromonas gingivalis in the biofilm environment. RNA-Sequencing with the Illumina platform was then utilized to identify C. albicans gene expression and functional pathways involved during such interactions in dual-species and a 4-species biofilm model. Results indicated that C. albicans was capable of supporting growth of all three bacteria, with a significant increase in colony counts of each bacteria in the dual-species biofilm (p < 0.05). We identified specific functional enrichment of pathways in our 4-species community as well as transcriptional profiles unique to the F. nucleatum and S. gordonii dual-species biofilms, indicating a species-specific effect on C. albicans. Candida-related hemin acquisition and heat shock protein mediated processes were unique to the organism following co-culture with anaerobic and aerobic bacteria, respectively, suggestive that such pathways may be feasible options for therapeutic targeting to interfere with these fungal-bacterial interactions. Targeted antifungal therapy may be considered as an option for biofilm destabilization and treatment of complex communities. Moving forward, we propose that further studies must continue to investigate the role of this fungal organism in the context of the interkingdom nature of oral diseases.

Right-sided infective endocarditis: characterization and prognosis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Right-sided infective endocarditis (RIE) involves native/prosthetic valves and any intracardiac devices present in the right cavities. It's caused by the seeding of any of these structures by bacterial or, less commonly, fungal organisms. It's commonly associated with intravenous drug use, intracardiac devices and central venous catheters, all of which became more prevalent over the past 20 years. Purpose We aimed to characterize the patients with right-sided infective endocarditis, including device endocarditis, admitted to our center and compare them with patients admitted with left-sided infective endocarditis (LIE). Methods We performed a retrospective study of a group of patients (pts) with infective endocarditis (IE) admitted to our center from 2000 to 2020. Pts were categorized with right-sided endocarditis when presented with endocarditis of the native/prosthetic valves right-sided and intracardiac devices. We considered, as composite endpoint, deaths, embolic events and recurrence of endocarditis in a medium follow-up of 37.4 ± 46.0 months. Results A total of 160 pts (106 males, mean age 66,3 ± 16 years) with the diagnosis of IE were included. 32 pts had RIE (11 with involvement of tricuspid valve and 23 with device involvement) and 126 had LIE (100 of native valve and 26 of prosthetic valve). We had 56 (15.5%) pts referred to surgery during hospitalization and 27 (7.5%) died during hospitalization. Compared with LIE, most of the pts with RIE were males (84% versus 61%, p= 0,015). The mean age was similar between the groups (p= 0,584). Pts with RIE had a lesser prevalence of known valvular heart disease (48% versus 21%, p= 0,007). Concerning complications of endocarditis, pts with RIE had less prevalence of fistula (18% versus 0%, p= 0,021). During hospitalization, the proportion of pts undergoing surgery was significantly less in patients with RIE (31% vs 61%, p=0,001). Considering the subgroup of patients with device endocarditis, 14 patients undergo device extraction (8 percutaneous and 6 surgical extraction). During a mean follow-up duration of 37.4 ± 46.0months, pts with the diagnosis of RIE had better outcomes for the composite endpoint (61% vs 33%, p=0.003). Even when we considered the events during the hospitalization (namely embolic events or death), this subgroup had fewer events (83% vs 63%, p=0.034). In a multivariate regression analysis, after adjusting for all the confounders (previous cardiac failure, development of severe valvular regurgitation, presence of fistula/perforation and development of abscess), RIE was an independent predictor of less prevalence of the composite endpoint (HR 0.38; 95% CI: 0.19-0.79). Conclusions RIE was associated with a better outcome, when considering death, embolic events, or recurrence of endocarditis. The patients with right-sided endocarditis were also less frequently submitted to surgery compared to others.