SARS-CoV-2 Post-Infection and Sepsis by Saccharomyces cerevisiae: A Fatal Case Report-Focus on Fungal Susceptibility and Potential Virulence Attributes.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for approximately 6.8 million deaths worldwide, threatening more than 753 million individuals. People with severe coronavirus disease-2019 (COVID-19) infection often exhibit an immunosuppression condition, resulting in greater chances of developing co-infections with bacteria and fungi, including opportunistic yeasts belonging to the Saccharomyces and Candida genera. In the present work, we have reported the case of a 75-year-old woman admitted at a Brazilian university hospital with an arterial ulcer in the left foot, which was being prepared for surgical amputation. The patient presented other underlying diseases and presented positive tests for COVID-19 prior to hospitalization. She received antimicrobial treatment, but her general condition worsened quickly, leading to death by septic shock after 4 days of hospitalization. Blood samples collected on the day she died were positive for yeast-like organisms, which were later identified as Saccharomyces cerevisiae by both biochemical and molecular methods. The fungal strain exhibited low minimal inhibitory concentration values for the antifungal agents tested (amphotericin B, 5-flucytosine, caspofungin, fluconazole and voriconazole), and it was able to produce important virulence factors, such as extracellular bioactive molecules (e.g., aspartic peptidase, phospholipase, esterase, phytase, catalase, hemolysin and siderophore) and biofilm. Despite the activity against planktonic cells, the antifungals were not able to impact the mature biofilm parameters (biomass and viability). Additionally, the S. cerevisiae strain caused the death of Tenebrio molitor larvae, depending on the fungal inoculum, and larvae immunosuppression with corticosteroids increased the larvae mortality rate. In conclusion, the present study highlighted the emergence of S. cerevisiae as an opportunistic fungal pathogen in immunosuppressed patients presenting several severe comorbidities, including COVID-19 infection.

Structure Elucidation, Antimicrobial and Cytotoxic Activities of a Halimane Isolated from Vellozia kolbekii Alves (Velloziaceae).

A new halimane diterpene was isolated from Vellozia kolbekii Alves (Velloziaceae) and identified as (5R,8R,9S,13R)-halim-1,10-ene-15,16-diol (1). It showed cytotoxicity against three human cancer cell lines, SF-295 (glioblastoma), MDA-MB-435 (melanoma), and HCT-8 (colon adenocarcinoma). In the mechanism of cytotoxic action, halimane 1 interferes in two major phases of the cell cycle: in S phase, in which DNA synthesis occurs and where it is very sensitive to damage, and G2M phase which is the phase of preparation for mitosis and mitosis itself, showing apoptosis-inducing properties. Antimicrobial activity towards Gram-positive and Gram-negative bacteria was studied and, against Bacillus cereus, B. subtilis, Escherichia coli, and Pseudomonas aeruginosa, a MIC value of 0.025 µM was observed for halimane 1, which is more active than the positive control chloramphenicol.

Aureonitol, a Fungi-Derived Tetrahydrofuran, Inhibits Influenza Replication by Targeting Its Surface Glycoprotein Hemagglutinin.

The influenza virus causes acute respiratory infections, leading to high morbidity and mortality in groups of patients at higher risk. Antiviral drugs represent the first line of defense against influenza, both for seasonal infections and pandemic outbreaks. Two main classes of drugs against influenza are in clinical use: M2-channel blockers and neuraminidase inhibitors. Nevertheless, because influenza strains that are resistant to these antivirals have been described, the search for novel compounds with different mechanisms of action is necessary. Here, we investigated the anti-influenza activity of a fungi-derived natural product, aureonitol. This compound inhibited influenza A and B virus replication. This compound was more effective against influenza A(H3N2), with an EC50 of 100 nM. Aureonitol cytoxicity was also very low, with a CC50 value of 1426 µM. Aureonitol inhibited influenza hemagglutination and, consequently, significantly impaired virus adsorption. Molecular modeling studies revealed that aureonitol docked in the sialic acid binding site of hemagglutinin, forming hydrogen bonds with highly conserved residues. Altogether, our results indicate that the chemical structure of aureonitol is promising for future anti-influenza drug design.

Virulence of Metarhizium anisopliae and Beauveria bassiana to Ctenocephalides felis felis.

Ctenocephalides felis felis is a flea species that parasitizes dogs and cats. The current study verified the in vitro virulence of the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana to eggs and adults of C. felis felis. The fungal isolates were cultivated on rice grains in plastic bags. Conidial suspensions were then prepared by immersing the grains in Tween 80 aqueous solution (0.01%). Eggs and adults of C. felis felis were obtained from a laboratory colony. Experiments were composed of one control and four treatment groups (10(5), 10(6), 10(7), and 10(8) conidia mL(-1)). Both insect pathogens inhibited egg hatchability and caused adult mortality. Among isolates used in this study, M. anisopliae (isolate E9) was the most successful at inhibiting hatching, while B. bassiana (isolate 986) was the most powerful for causing mortality in adults. The results indicate that these entomopathogenic fungi have promising potential for use in controlling both C. felis felis egg and adult stages.

Avaliação in vitro dos fungos aspergillus flavus e penicillium corylophilum em larvas de musca domestica diptera muscidade / In vitro avaliation of the fungus aspergillus flavus and penicillium corylophilum in larvae of musca domestica diptera muscidade

The present study was aimed at the evaluation of two isolates of Aspergillus flavus and two isolates of Penicilium corylophilum on third stage larvae of Musca domestica. The samples tested were isolated directly from M. domestica specimens. Third stage larvae were obtained from pupas of a laboratory colony. Four batches with 20 larvae were used for each of conidia dilution tested (105 to 108 conidia/ml). Larvae were dipped for one minute into conidia dilution, being then moved to dishes and kept under controlled environmental conditions. Two control groups were used: one received a treatment with spreading adhesive and the other one with no treatment at all. Larval surviving rates were: 57.50 percent and 86.25 percent for groups treated with 108 conidia/ml of A. flavus; and 63.75 percent and 72.50 percent for those who had received the same concentration of P. corylophilum conidia. Larval mortality rates were greater for groups that received higher conidia concentrations, and also increased directly proportional to exposition time. Adult hatching rates on treated groups, were affected by fungi treatment. It was concluded that A. flavus and P. corylophilum presented detrimental effects for third stage larvae of M. domestica

Avaliacao in vitro dos fungos aspergillus flavus e penicillium corylophilum em adultos de musca domestica / In vitro avaliation of the fungus aspergillus flavus and penicillium corylophilum in adults of musca domestica

O objetivo do presente estudo foi o de avaliar o potencial de dois isolados fúngicos de Aspergillus flavus e dois isolados de Penicillium corylophilum sobre adultos de Musca domestica. Para a realizacao dos bioensaios foram selecionados dois isolados de cada especie fúngica. Os adultos de M. domestica para os bioensaios foram obtidos a partir de pupas da colonia desta especie. Moscas adultas recem emergidas foram separadas en quatro grupos con dez moscas para cada uma das diluicoes das suspensoes conidiais (10 elevado a 5 a 10 elevado a 8 conídios/ml). Foram realizadas pulverizacoes de 2,5 ml das suspensoes conidiais para cada repeticao. Dois grupos controles foram mantidos, no primeiro as moscas foram tratadas com espalhante adesivo e o segundo sem nenhum tratamento. Os insetos adultos foram sensíveis aos tratamentos com diferentes isolados fúngicos, princeipalmente nos tratamentos com suspensoes com maiores concentracoes conidiais. No bioensaio com um dos isolados de A. flavus ocorreu a mortalidade de 100 percento das moscas no terceiro dia após a infeccao. Nos bioensaios com os dois isolados de P. corylophilum, 100 percento das moscas tratadas morreram até o sétimo dia após infeccao. O ritmo de mortalidade foi mais lento nos tratamentos com menores concentracoes conidiais prolongandose até o 15º dia