The interactome of Cryptococcus neoformans Rmt5 reveals multiple regulatory points in fungal cell biology and pathogenesis

Protein arginine methylation is a key post-translational modification in eukaryotes that modulates core cellular processes, including translation, morphology, transcription, and RNA fate. However, this has not been explored in Cryptococcus neoformans, a human-pathogenic basidiomycetous encapsulated fungus. We characterized the five protein arginine methyltransferases in C. neoformans and highlight Rmt5 as critical regulator of cryptococcal morphology and virulence. An rmt5∆ mutant was defective in thermotolerance, had a remodeled cell wall, and exhibited enhanced growth in an elevated carbon dioxide atmosphere and in chemically induced hypoxia. We revealed that Rmt5 interacts with post-transcriptional gene regulators, such as RNA-binding proteins and translation factors. Further investigation of the rmt5∆ mutant showed that Rmt5 is critical for the homeostasis of eIF2α and its phosphorylation state following 3-amino-1,2,4-triazole-induced ribosome stalling. RNA sequencing of one rmt5∆ clone revealed stable chromosome 9 aneuploidy that was ameliorated by complementation but did not impact the rmt5∆ phenotype. As a result of these diverse interactions and functions, loss of RMT5 enhanced phagocytosis by murine macrophages and attenuated disease progression in mice. Taken together, our findings link arginine methylation to critical cryptococcal cellular processes that impact pathogenesis, including post-transcriptional gene regulation by RNA- binding proteins.

A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans

Cryptococcus neoformans and Cryptococcus gattii can cause cryptococcosis, which has a high mortality rate. To treat the disease, amphotericin B and fluconazole are often used in clinic.

Role of F-box Protein Cdc4 in Fungal Virulence and Sexual Reproduction of Cryptococcus neoformans

Cryptococcus neoformans is an opportunistic yeast-like pathogen that mainly infects immunocompromised individuals and causes fatal meningitis. Sexual reproduction can promote the exchange of genetic material between different strains of C. neoformans, which is one of the reasons leading to the emergence of highly pathogenic and drug-resistant strains of C. neoformans. Although much research has been done on the regulation mechanism of Cryptococcus sexual reproduction, there are few studies on the sexual reproduction regulation of Cryptococcus by the ubiquitin-proteasome system. This study identified an F-box protein, Cdc4, which contains a putative F-box domain and eight WD40 domains. The expression pattern analysis showed that the CDC4 gene was expressed in various developmental stages of C. neoformans, and the Cdc4 protein was localized in the nucleus of cryptococcal cells. In vitro stress responses assays showed that the CDC4 overexpression strains are sensitive to SDS and MMS but not Congo red, implying that Cdc4 may regulate the cell membrane integrity and repair of DNA damage of C. neoformans. Fungal virulence assay showed that although the cdc4Δ mutant grows normally and can produce typical virulence factors such as capsule and melanin, the cdc4Δ mutant completely loses its pathogenicity in a mouse systemic-infection model. Fungal mating assays showed that Cdc4 is also essential for fungal sexual reproduction in C. neoformans. Although normal mating hyphae were observed during mating, the basidiospores’ production was blocked in bilateral mating between cdc4Δ mutants. Fungal nuclei development assay showed that the nuclei failed to undergo meiosis after fusion inside the basidia during the bilateral mating of cdc4Δ mutants, indicating that Cdc4 is critical to regulating meiosis during cryptococcal mating. In summary, our study revealed that the F-box protein Cdc4 is critical for fungal virulence and sexual reproduction in C. neoformans.

Clinical features of invasive fungal disease in children with no underlying disease

There is limited research into Invasive fungal disease (IFD) in children with no underlying disease. We undertook a retrospective study of children with IFD who did not suffer from another underlying disease, from June 2010 to March 2018 in Changsha, China. Nine children were identified. Eosinophil counts were elevated in six cases. The level of procalcitonin (PCT) was elevated in six cases. Fungal culture was positive in all patients, including eight cases of Cryptococcus neoformans and one case of Candida parapsilosis. 8.33 days following antifungal treatment, the body temperature of the eight patients affected by cryptococcal disease had returned to normal. Our study indicates that the primary pathogen in IFD was Cryptococcus neoformans in children who had no other underlying disease. Eosinophils can be considered to be indicators of cryptococcal infection. IFD in children with no other underlying disease has a satisfactory prognosis.

Protection of Mice against Experimental Cryptococcosis by Synthesized Peptides Delivered in Glucan Particles

Cryptococcosis, due to infection by fungi of the Cryptococcus neoformans species complex, is responsible for substantial morbidity and mortality in immunocompromised persons, particularly those with AIDS. Cryptococcal vaccines are a public health priority yet are not available for human use.

Perbandingan Aktivitas Antimikroba Ekstrak Etanol dari Tiga Spesies Ganoderma Asal Pulau Lombok

The use of antibiotics is one of the most important ways to deal with the spread and treatment of pathogenic microbial infections. The search for new antibiotic sources continues to be carried out to anticipate the emergence of microbial resistance. One of the natural resources that has the potential as an antimicrobial source is a member of the macrofungi of the Genus Ganoderma. The purpose of this study was to evaluate the antimicrobial performance of the ethanol extracts of Ganoderma lucidum, G. applanatum dan Ganorderma sp. against fungi (Candida albicans dan Cryptococcus neoformans), gram positive bacteria (Bacillus cereus dan Staphylococcus aureus) and gram negative bacteria (Escherichia coli dan Shigella sp.). Macrofungi samples were taken from the forest area of Nature Tourism Park (TWA) Gunung Tunak, TWA Kerandangan, TWA Suranadi, TWA Nuraksa Sesaot, TWA Lemor and Pusuk forest. The stages of the method performed are sample collection, sample preparation, extraction, and testing of antimicrobial activity using the well difusion method. The ethanol extract concentrations for testing were 20%, 40%, 60% and 80%. The results showed that the three Ganoderma species had anti-fungal and antibacterial activity and that different levels of concentration had an effect on inhibition. The size of the inhibition zone is directly proportional to the higher the extract concentration. The antimicrobial activity of the ethanol extract of G. lucidum was higher when compared to G. applanatum and Ganoderma sp. both against fungi (Candida albicans and Cryptococcus neoformans) as well as against gram-positive and gram-negative test bacteria. In addition, G. applanatum showed very weak inhibition against both groups of tested bacteria. Key words: candidiasis; cryptococcosis; comorbid infections; macerations; pathogens

Мікробіологічна та вірусологічна характеристика морської води Одеської затоки та акваторії острова Зміїний

Проведені комплексні мікробіологічні, вірусологічні, санітарно–екологічні та генетичні дослідження морської води Одеської затоки Чорного моря та акваторії острова Зміїний дозволили виявити мікробіологічне (умовно-патогенні, санітарно-показові бактерії, віруси) та хімічне (важкі метали, нафтопродукти, ПАР та інше) забруднення в контактній зоні моря. У морської води акваторії острова Зміїний як в прибережній зоні, так і на відстані 100 м від берега, незважаючи на сильний нагонний вітер та морське хвилювання, були виявлені патогенні для людини віруси гепатиту А і ротавірусу. Вперше з акваторії острова Зміїний виділено та ідентифіковано 7 видів дріжджів з 5 родів (Cryptococcus albidus, Cryptococcus neoformans, Aerobasidium pullulans, Candida albicans, Rhodotorula rubra, Rhodotorula glutinis, Rhodosporidium paludigenum). Домінування видів чорної та рожевої дріжджової мікробіоти є характерним для водних екосистем. Встановлено високий індекс таксономічної різноманітності - 10 родів домінуючих бактерій в морській воді Одеської затоки Чорного моря. Вперше було встановлено, що до складу домінуючих гетеротрофних бактерій входять представники малодослідженої групи ковзних бактерій, що беруть участь у процесах деструкції і мінералізації складних природних та синтетичних сполук в морському середовищі в умовах хронічного антропогенного забруднення, зокрема в акваторії Одеського заливу найбільш забрудненої побутовими стоками - в районі Дачі Ковалевського. Ліполітичні бактерії, здатні брати участь у процесах самоочищення морського середовища, виявлено в прибережній зоні о. Зміїний. Найбільша чисельність тіонових бактерій була зерєєстрована в районі Дачі Ковалевського - у місці із сильним антропогенним навантаженням по синтетичним поверхнево-активним речовинами, Сu(II), Ct(VI), Zn(II) та сезонно по нафтопродуктам. У бактеріальних тест-системах Salmonella typhimurium ТА100 та Salmonella typhimurium ТА98 встановлений генотиксичний та мутагенний потенціал забруднення морської води Одеського узбережжя та акваторії острову Зміїний.

Criptococose Cutânea Primária em Paciente Imunocompetente: Um Relato de Caso

A criptococose é uma infecção sistémica causada por Cryptococcus neoformans, levedura oportunista encapsulada. Esta infeção ocorre principalmente em indivíduos imunocomprometidos e os sintomas variam de acordo com a integridade do sistema imunológico. A criptococose cutânea afeta aproximadamente 20% dos pacientes com criptococose disseminada, mas a criptococose cutânea primária (PCC) sem infecção sistémica é rara. Um paciente do sexo masculino de 76 anos, com doença pulmonar obstrutiva crónica, hipertensão arterial e dislipidemia, apresentou-se com placa cutânea inflamatória violácea com bolhas que progrediu apesar de ceftriaxone endovenoso por 7 dias, sem sucesso. A biópsia incisional revelou o diagnóstico histopatológico de criptococose cutânea. As lesões resolveram após tratamento com fluconazol 300 mg/dia durante 3 meses. Não se detectou doença sistémica e não havia qualquer evidência de imunossupressão. Enfatiza-se a importância da inclusão da criptococose cutânea no diagnóstico diferencial das lesões cutâneas, mesmo em pacientes sem terapia imunossupressora. As manifestações cutâneas da infecção podem ser o primeiro indício para uma doença disseminada, pelo que o seu reconhecimento precoce é fundamental para um bom prognóstico.

Bionized nanoferrite particles alter the course of experimental Cryptococcus neoformans pneumonia

Cryptococcosis is a devastating fungal disease associated with high morbidity and mortality even when treated with antifungal drugs. Bionized nanoferrite (BNF) nanoparticles are powerful immunomodulators, but their efficacy for infectious diseases has not been investigated. Administration of BNF nanoparticles to mice with experimental cryptococcal pneumonia altered the outcome of infection in a dose response manner as measured by colony forming units and survival. The protective effects were higher at lower doses, with reductions in IL-2, IL-4 and TNF-α, consistent with immune modulation whereby reductions in inflammation translate into reduced host damage, clearance of infection and longer survival.