Review
Microbiology
Silvia Radosa, Falk Hillmann
Summary: Free living amoebae exhibit similarities with innate immune cells and may have served as a training ground for environmental pathogens. Virulence determinants of some fungal pathogens can resist both innate immune cells and environmental phagocytic predators.
CURRENT OPINION IN MICROBIOLOGY
(2021)
Review
Immunology
Herdson Renney de Sousa, Stefania de Frazao, Getulio Pereira de Oliveira Junior, Patricia Albuquerque, Andre Moraes Nicola
Summary: Cryptococcosis, caused by Cryptococcus spp, has a high mortality rate and lacks effective prevention and treatment methods. Understanding fungal virulence and host responses could lead to improved therapies. Studies using clinical isolates to correlate laboratory and patient data have provided valuable insights into the pathophysiology of cryptococcosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Medicine, Research & Experimental
Joseph Heitman
Summary: This Viewpoint is associated with the 25th anniversary of the American Society for Clinical Investigation's Stanley J. Korsmeyer Award, which recognizes scientific excellence, meritorious research, intellectual integrity, and mentoring of future researchers. The 2018 award honored Joseph Heitman for his contributions to understanding microbial pathogen evolution, disease causation, drug resistance, and discovery of immunosuppressive drug targets. Dr. Heitman has mentored numerous students, fellows, and researchers who have pursued successful careers in medicine and biomedical research.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Microbiology
Hau Lam Choy, Elizabeth A. A. Gaylord, Tamara L. L. Doering
Summary: Cryptococcus neoformans is a pathogenic fungus that causes over 100,000 deaths worldwide each year. Only three drugs are available for treating cryptococcosis, but their usage is limited by factors such as toxicity, availability, cost, and resistance. Ergosterol, the most abundant sterol in fungi, plays a key role in modulating membrane behavior. We discovered a cryptococcal ergosterol transporter, Ysp2, and demonstrated its important roles in various aspects of cryptococcal biology and disease progression. These findings provide insights into the role of ergosterol homeostasis in the virulence of C. neoformans, expand our understanding of a pathway with therapeutic significance, and open up new research possibilities.
Review
Chemistry, Multidisciplinary
Israel Diniz-Lima, Leonardo Marques da Fonseca, Elias Barbosa da Silva-Junior, Joyce Cristina Guimaraes-de-Oliveira, Leonardo Freire-de-Lima, Danielle Oliveira Nascimento, Alexandre Morrot, Jose Osvaldo Previato, Lucia Mendonca-Previato, Debora Decote-Ricardo, Celio Geraldo Freire-de-Lima
Summary: Cryptococcosis is caused by pathogenic fungi, including Cryptococcus neoformans and Cryptococcus gattii. The latter causes severe undiscriminating infections in immunocompetent individuals and is becoming more prevalent due to climatic factors. The immunopathology of cryptococcosis caused by C. gattii is still poorly understood, but research has helped to uncover its different variants.
APPLIED SCIENCES-BASEL
(2022)
Article
Microbiology
Iara Bastos de Andrade, Dario Correa-Junior, Vinicius Alves, Maria Helena Galdino Figueiredo-Carvalho, Marcos Vinicius Santos, Marcos Abreu Almeida, Alessandro Fernandes Valdez, Leonardo Nimrichter, Rodrigo Almeida-Paes, Susana Frases
Summary: This study investigated the effects of cyclosporine on Cryptococcus neoformans, finding that it altered the morphology, cell wall structure, and secretion characteristics of the fungus. Cyclosporine at half the minimum inhibitory concentration resulted in irregular shapes and elongated projections of yeast cells, increased chitin and lipid bodies in the fungal cell wall, and reduced cell body size, capsule diameter, and urease secretion. Additionally, cyclosporine affected the viscosity, electronegativity, and conductance of secreted polysaccharides. These findings highlight the significance of cyclosporine in shaping C. neoformans and its potential implications for antifungal drug development.
Article
Immunology
Ya-li Yang, Yi-bin Fan, Lei Gao, Chao Zhang, Ju-lin Gu, Wei-hua Pan, Wei Fang
Summary: This study elucidates the role of Csn1201 protein in cryptococcal fitness and host immunity. Deletion of Csn1201 blocks the pulmonary infection and extrapulmonary dissemination of Cryptococcus neoformans, while enhancing the host immune response.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Kenya E. Fernandes, James A. Fraser, Dee A. Carter
Summary: Cryptococcosis is a devastating cause of death and disease worldwide. During infection, Cryptococcus cells can undergo substantial changes to their size and shape. In this study, researchers found that hypervirulent strains of Cryptococcus had larger capsules, greater variation in cell size, and produced more microcells and shed capsule. These hypervirulent strains had a mutation in the SGF29 gene, which encodes a component of the SAGA complex involved in epigenetic regulation. Analysis of clinical isolates also showed a correlation between loss-of-function mutations in SGF29 and higher patient death rates. The study suggests that the ability to undergo morphological variation is linked to virulence in Cryptococcus, and this can occur through epigenetic mechanisms.
Article
Microbiology
Piotr R. Stempinski, Kristie D. Goughenour, Lukas M. du Plooy, J. Andrew Alspaugh, Michal A. Olszewski, Lukasz Kozubowski
Summary: This study reveals the importance of the Flc1 protein in maintaining calcium homeostasis and vacuolar biogenesis in Cryptococcus neoformans. Deletion of Flc1 leads to an increase in cytosolic calcium concentration, an elevation of Crz1 transcription factor in the nucleus, and an aberrant accumulation of cell wall chitin. Flc1 is also involved in vacuolar fusion and capsule formation. The absence of Flc1 results in the loss of survival ability and virulence in Cryptococcus.
Article
Microbiology
Gustavo Dornelles, Glauber R. de S. Araujo, Marcus Rodrigues, Vinicius Alves, Rodrigo Almeida-Paes, Susana Frases
Summary: Fungal infections, especially in immunocompromised patients, pose a global public health challenge. This study focused on Rhodotorula mucilaginosa, a basidiomycetous yeast that has emerged as an opportunistic pathogen. The polysaccharides of R. mucilaginosa were characterized and compared with those of Cryptococcus neoformans, revealing correlations with virulence and pathogenicity. The study also highlighted the need for more reliable diagnostic tests to improve the differential diagnosis of basidiomycetous yeast infections. This research contributes to a better understanding of yeast pathogenicity and emphasizes the importance of accurate diagnostic tests.
Article
Microbiology
Norida Velez, Lucia Monteoliva, Zilpa-Adriana Sanchez-Quitian, Ahinara Amador-Garcia, Rocio Garcia-Rodas, Andres Ceballos-Garzon, Concha Gil, Patricia Escandon, Oscar Zaragoza, Claudia-Marcela Parra-Giraldo
Summary: This study found that the combination of iron and copper can enhance the pathogenicity of Cryptococcus neoformans and increase the abundance of proteins related to virulence factors. This suggests that the uptake of metals may affect the pathogenicity of fungi.
Article
Microbiology
Cheng-Li Fan, Tong-Bao Liu
Summary: The study identified the vacuolar morphogenesis protein Vam6-like protein Vlp1 as essential for the pathogenicity of Cryptococcus neoformans. Deletion of the VLP1 gene resulted in abnormal capsule formation and melanin production of C. neoformans, and stress tolerance assays indicated that Vlp1 may regulate cell membrane integrity. Moreover, vlp1 Delta mutants exhibited decreased virulence in a mouse systematic infection model of cryptococcosis, suggesting an important role of Vlp1 in fungal pathogenicity.
Article
Immunology
Ting Wu, Cheng-Li Fan, Lian-Tao Han, Yuan-Bing Guo, Tong-Bao Liu
Summary: This study reveals the critical role of the F-box protein Cdc4 in fungal virulence and sexual reproduction in C. neoformans. Cdc4 regulates cell membrane integrity and DNA damage repair, as well as meiosis during fungal mating.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Felipe H. Santiago-Tirado, Thomas Hurtaux, Jennifer Geddes-McAlister, Duy Nguyen, Volkhard Helms, Tamara L. Doering, Karin Roemisch
Summary: The fungal pathogen Cryptococcus neoformans is distinguished by a critical cell-wall-anchored polysaccharide capsule for virulence. The secretory pathway is crucial for the biogenesis of both cell wall and capsule. Sbh1, a protein involved in this pathway, regulates the entry of virulence factors into the secretory pathway of C. neoformans, thereby impacting fungal pathogenicity. This study provides insights into the mechanisms underlying the regulation of protein secretion and the pathogenicity of C. neoformans.
Article
Biology
Daniel F. Q. Smith, Quigly Dragotakes, Madhura Kulkarni, J. Marie Hardwick, Arturo Casadevall
Summary: Melanin production in insects plays a crucial role in the immune response against microbial infections. This study provides direct evidence that melanin encapsulation is fungicidal and enhances immune melanization. The research also demonstrates the antifungal mechanism of immune melanization in Galleria mellonella hosts.
COMMUNICATIONS BIOLOGY
(2022)
Article
Microbiology
Mai Lee Yang, John Uhrig, Kiem Vu, Anil Singapuri, Michael Dennis, Angie Gelli, George R. Thompson
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2016)
Article
Cell Biology
Phylicia A. Aaron, Mantana Jamklang, John P. Uhrig, Angie Gelli
CELLULAR MICROBIOLOGY
(2018)
Article
Multidisciplinary Sciences
Sarisa Na Pombejra, Mantana Jamklang, John P. Uhrig, Kiem Vu, Angie Gelli
Article
Chemistry, Medicinal
Phylicia A. Aaron, Angie Gelli
ACS INFECTIOUS DISEASES
(2020)
Article
Microbiology
Phylicia A. Aaron, Kiem Vu, Angie Gelli
Article
Chemistry, Medicinal
Shivani Bansal, Kiem Vu, Ruiwu Liu, Yousif Ajena, Wenwu Xiao, Suvidha M. Menon, Amelia Bennett, Angie Gelli, Kit S. Lam
Summary: This work describes the discovery of bead-bound fungal giant unilamellar vesicles (GUVs) over mammalian GUVs, and the optimization of a peptide, K-oLBF127, with higher antifungal activity, lower hemolytic activity, and cytotoxicity. Animal experiments showed that K-oLBF127 has the potential to effectively reduce fungal burden in vivo.
ACS INFECTIOUS DISEASES
(2022)