A Limited Number of Amino Acid Permeases Are Crucial for Survival and Virulence.

One unique attribute of is its ability to procure essential monomers from its surroundings to survive in diverse environments. Preferentially, sugars are the energy sources for this opportunistic pathogenic fungus under the carbon catabolite repression (CCR); however, sugar restriction induces alternative use of low molecular weight alcohol, organic acids, and amino acids. The expression of transmembrane amino acid permeases (Aaps) allows to utilize different amino acids and their conjugates, notwithstanding under the nitrogen catabolite repression (NCR).

Aspergillus fumigatus secretes a protease(s) that displays in silico binding affinity towards the SARS-CoV-2 spike protein and mediates SARS-CoV-2 pseudovirion entry into HEK-293T cells.

Background: The novel coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Data from the COVID-19 clinical control case studies showed that this disease could also manifest in patients with underlying microbial infections such as aspergillosis. The current study aimed to determine if the Aspergillus (A.

Cryptococcal proteases exhibit the potential to activate the latent SARS-CoV-2 spike protein.

Background: The COVID-19 pandemic has affected more than 650 million people and resulted in over 6.8 million deaths. Notably, the disease could co-manifest with microbial infections, like cryptococcosis, which also presents as a primary lung infection.

Primaquine, an antimalarial drug that controls the growth of cryptococcal cells.

Introduction: The treatment of Cryptococcus neoformans with fluconazole and amphotericin B is, at times, characterised by clinical failure. Therefore, this study sought to re-purpose primaquine (PQ) as an anti-Cryptococcus compound.

Method: The susceptibility profile of some cryptococcal strains towards PQ was determined using EUCAST guidelines, and PQ's mode of action was examined.

Cryptococcal Protease(s) and the Activation of SARS-CoV-2 Spike (S) Protein.

In this contribution, we report on the possibility that cryptococcal protease(s) could activate the SARS-CoV-2 spike (S) protein. The S protein is documented to have a unique four-amino-acid sequence (underlined, SPRRAR↓S) at the interface between the S1 and S2 sites, that serves as a cleavage site for the human protease, furin. We compared the biochemical efficiency of cryptococcal protease(s) and furin to mediate the proteolytic cleavage of the S1/S2 site in a fluorogenic peptide.

The first survey of cryptococcal cells in bird droppings across Bloemfontein, South Africa.

Background And Aim: Cryptococcal yeast cells are spread across different ecosystems through bird movement and are deposited in bird guano. These cells may be inhaled by humans and lead to cryptococcal pneumonia. In individuals with reduced immune T-cell populations, cells may disseminate to the brain and cause the often-deadly cryptococcal meningitis.

The Possible Role of Microbial Proteases in Facilitating SARS-CoV-2 Brain Invasion.

SARS-CoV-2 has been shown to display proclivity towards organs bearing angiotensin-converting enzyme (ACE2) expression cells. Of interest herein is the ability of the virus to exhibit neurotropism. However, there is limited information on how this virus invades the brain.

The Repurposing of Acetylsalicylic Acid as a Photosensitiser to Inactivate the Growth of Cryptococcal Cells.

Photodynamic treatment (PDT) is often successful when used against aerobic microbes, given their natural susceptibility to oxidative damage. To this end, the current study aimed to explore the photodynamic action of acetylsalicylic acid (ASA; aspirin, which is commonly used to treat non-infectious ailments), when administered to respiring cryptococcal cells. The treatment of cryptococcal cells, i.

Overview of the Development, Impacts, and Challenges of Live-Attenuated Oral Rotavirus Vaccines.

Safety, efficacy, and cost-effectiveness are paramount to vaccine development. Following the isolation of rotavirus particles in 1969 and its evidence as an aetiology of severe dehydrating diarrhoea in infants and young children worldwide, the quest to find not only an acceptable and reliable but cost-effective vaccine has continued until now. Four live-attenuated oral rotavirus vaccines (LAORoVs) (Rotarix, RotaTeq, Rotavac, and RotaSIIL) have been developed and licensed to be used against all forms of rotavirus-associated infection.

Environmental Factors That Contribute to the Maintenance of Pathogenesis.

The ability of microorganisms to colonise and display an intracellular lifestyle within a host body increases their fitness to survive and avoid extinction. This host-pathogen association drives microbial evolution, as such organisms are under selective pressure and can become more pathogenic. Some of these microorganisms can quickly spread through the environment via transmission.

Complementary Use of Microscopic Techniques and Fluorescence Reading in Studying Cryptococcus-Amoeba Interactions.

To simulate Cryptococcus infection, amoeba, which is the natural predator of cryptococcal cells in the environment, can be used as a model for macrophages. This predatory organism, similar to macrophages, employs phagocytosis to kill internalized cells. With the aid of a confocal laser-scanning microscope, images depicting interactive moments between cryptococcal cells and amoeba are captured.

Functional Characterization of Cryptococcal Genes: Then and Now.

Site-directed mutagenesis enables researchers to switch a gene of interest off for functional characterization of the gene. In the pathogenic yeasts, and sister species , this is almost exclusively achieved by introducing DNA into cells through either biolistic transformation or electroporation. The targeted gene is then disrupted by homologous recombination (HR) between the gene and the transforming DNA.

Copper Acyl Salicylate Has Potential as an Anti-Cryptococcus Antifungal Agent.

The antifungal activity of aspirin against cryptococcal cells has been reported. However, the unwanted effects of aspirin may limit its clinical application. Conceivably, a derivative of aspirin could overcome this challenge.

The Repurposing of Anti-Psychotic Drugs, Quetiapine and Olanzapine, as Anti-Cryptococcus Drugs.

The management of cryptococcal infections is often difficult. This can, in part, be attributed to the fungistatic nature of fluconazole, which may result in cells disseminating to give rise to pathogen-emergent psychosis following brain inflammation. This chance at treatment failure has necessitated the current study wherein the antimicrobial quality of anti-psychotic drugs viz.

Elucidation of the Role of 3-Hydroxy Fatty Acids in -amoeba Interactions.

We previously reported that 3-hydroxy fatty acids promoted the survival of cryptococcal cells when acted upon by amoebae. To expand on this, the current study sought to explain how these molecules may protect cells. Our data suggest that 3-hydroxy fatty acids may subvert the internalization of cryptococcal cells via suppression of the levels of a fetuin A-like amoebal protein, which may be important for enhancing phagocytosis.

Pseudomonas aeruginosa produces aspirin insensitive eicosanoids and contributes to the eicosanoid profile of polymicrobial biofilms with Candida albicans.

The interaction of clinically relevant microorganisms is the focus of various studies, e.g. the interaction between the pathogenic yeast, Candida albicans, and the bacterium, Pseudomonas aeruginosa.

Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs.

The usage of fluconazole and amphotericin B in clinical settings is often limited by, among other things, drug resistance development and undesired side effects. Thus, there is a constant need to find new drugs to better manage fungal infections. Toward this end, the study described in this paper considered the repurposing of aspirin (acetylsalicylic acid) and ibuprofen as alternative drugs to control the growth of cryptococcal cells.

Candida albicans and Pseudomonas aeruginosa Interaction, with Focus on the Role of Eicosanoids.

Candida albicans is commonly found in mixed infections with Pseudomonas aeruginosa, especially in the lungs of cystic fibrosis (CF) patients. Both of these opportunistic pathogens are able to form resistant biofilms and frequently infect immunocompromised individuals. The interaction between these two pathogens, which includes physical interaction as well as secreted factors, is mainly antagonistic.

Cryptococcal 3-Hydroxy Fatty Acids Protect Cells Against Amoebal Phagocytosis.

We previously reported on a 3-hydroxy fatty acid that is secreted via cryptococcal capsular protuberances - possibly to promote pathogenesis and survival. Thus, we investigated the role of this molecule in mediating the fate of Cryptococcus (C.) neoformans and the related species C.

Method for identification of Cryptococcus neoformans and Cryptococcus gattii useful in resource-limited settings.

Aims: The high HIV/AIDS burden in Sub-Saharan Africa has led to cryptococcosis becoming a public health concern. In this resource-limited setting, conventional identification methods are mainly used to diagnose cryptococcal infections. However, these methods are often inconsistent, and importantly, cannot discriminate between the aetiological agents, Cryptococcus neoformans and C.

AIDS-related mycoses: the way forward.

The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries.

The presence of 3-hydroxy oxylipins in pathogenic microbes.

There is a sufficient body of work documenting the distribution of 3-hydroxy oxylipins in microbes. However, there is limited information on the role of these compounds in microbial pathogenesis. When derived from mammalian cells, these compounds regulate patho-biological processes, thus an understanding of 3-hydroxy oxylipin function and metabolism could prove important in shedding light on how these compounds mediate cellular pathology and physiology.

Distribution of 3-hydroxy oxylipins and acetylsalicylic acid sensitivity in Cryptococcus species.

Using a well tested antibody specific for 3-hydroxy oxylipins, we mapped the presence of these oxylipins in selected Cryptococcus (Filobasidiella) species. Immunofluorescence microscopy studies revealed that these compounds are deposited on cell wall surfaces, appendages, and collarettes. In vitro studies revealed that growth of Cryptococcus species was inhibited by acetylsalicylic acid (which is known to inhibit mitochondrial function, including the production of 3-hydroxy oxylipins) at concentrations as low as 1 mmol/L.

The influence of acetylsalicylic acid on oxylipin migration in Cryptococcus neoformans var. neoformans UOFS Y-1378.

In this paper we report the influence of acetylsalicylic acid on oxylipin migration in Cryptococcus neoformans var. neoformans UOFS Y-1378, previously isolated from human bone lesion. Transmission electron microscopy suggests that osmiophilic material originates in mitochondria and is deposited inside the yeast cell wall, from which it is excreted into the environment, along capsule protuberances, or through capsule detachments.