Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals

Autor: Joaquín Ariño, Nuria Trevijano-Contador, Oscar Zaragoza, Suélen Andreia Rossi, Guilhem Janbon, Haroldo Cesar de Oliveira, Ángel Zaballos, Irene Llorente, Rocío García-Rodas
Přispěvatelé: National Centre for Microbiology [Madrid], Instituto de Salud Carlos III [Madrid] (ISC), Faculdade de Ciências Farmacêuticas [São Paulo, Brazil], Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University (UNESP), Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens, Institut Pasteur [Paris], Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona (UAB), Departament de Bioquímica i Biologia Molecular, OZ is funded by grant SAF2014-54336-R and SAF2017-86192-R1 from the Spanish Ministry for Economics, Industry and Competitivity. JA is funded by grants BFU2014-54591-C2-1-P and BFU2017-82574-P (Spanish Ministry for Economics, Industry and Competitivity) and an 'Ajut 2014SGR-4' (Generalitat de Catalunya). NT-C was supported by a FPI fellowship (reference BES-2012-051837). SAR was supported by a fellowship from Coordenação de aperfeiçoamento de pessoal de nivel superior, CAPES, program Ciências Sem Fronteiras (202436/2015-2). HCdO is funded by postdoctoral fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-BEPE 2016/20631-3). RG-R is funded by a 'Juan de la Cierva' Contract from the Spanish Ministry for Economics, Industry and Competitivity (reference: IJCI-2015-25683)., We want to thank Dr. Joseph Heitman (Duke University Medical Center, Durham, North Carolina, United States of America), Dr. Robin May (Birmingham University, UK) and Dr. June Kwon-Chung (NIH, Bethesda, USA), for the gift of strains. I.L. participated in this work in the frame of the master in 'Microbiology Applied to Public Health and Research on Infectious Diseases' (Alcalá University and Instituto de Salud Carlos III). We would like to thank Pilar Jiménez Sancho (Genomics Unit, Core Scientific Services, Instituto de Salud Carlos III) for her technical assistance in the RNAseq experiments. We also would like to thank Dr. Manuel Lombardía (Proteomics Facility, National Centre for Biotechnology, Madrid, Spain), for his technical assistance in peptide synthesis., Institut Pasteur [Paris] (IP), Ministerio de Economía y Competitividad (España), Government of Catalonia (España), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil), Fundação de Amparo à Pesquisa do Estado de São Paulo (Brasil), Ministerio de Economía, Industria y Competitividad (España), Instituto de Salud Carlos III, Universidade Estadual Paulista (Unesp), Département de Mycologie, Universitat Autònoma de Barcelona, Albert Einstein College of Medicine
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
MESH: Signal Transduction
Cell
MESH: Quorum Sensing
Mice
Gene expression
MESH: RAW 264.7 Cells
MESH: Animals
Biology (General)
MESH: Phagocytosis
[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
biology
Chemistry
Quorum Sensing
Cryptococcosis
MESH: Host-Pathogen Interactions / physiology
MESH: Cryptococcosis / microbiology
3. Good health
Cell biology
medicine.anatomical_structure
Phenotype
Host-Pathogen Interactions
Signal transduction
Physiological parameters
Signal Transduction
MESH: Cryptococcus neoformans / cytology
MESH: Host-Pathogen Interactions / genetics
QH301-705.5
030106 microbiology
Immunology
Genes
Fungal

MESH: Phenotype
Microbiology
Models
Biological

03 medical and health sciences
MESH: Gene Expression Profiling
Phagocytosis
MESH: Mice
Inbred C57BL

Virology
Calnexin
Genetics
medicine
Animals
Humans
MESH: Macrophages / microbiology
Molecular Biology
MESH: Mice
Protein kinase C
Cryptococcus neoformans
MESH: Humans
Gene Expression Profiling
Macrophages
MESH: Cryptococcus neoformans / pathogenicity
MESH: Models
Biological

Metabolism
MESH: Cryptococcus neoformans / genetics
RC581-607
biology.organism_classification
In vitro
MESH: Male
Mice
Inbred C57BL

Cryptococcus
RAW 264.7 Cells
Carbon dioxide
Parasitology
Cell formation
Immunologic diseases. Allergy
MESH: Genes
Fungal
Zdroj: PLoS Pathogens
PLoS Pathogens, Public Library of Science, 2018, 14 (5), pp.e1007007. ⟨10.1371/journal.ppat.1007007⟩
Recercat. Dipósit de la Recerca de Catalunya
instname
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
PLoS Pathogens, 2018, 14 (5), pp.e1007007. ⟨10.1371/journal.ppat.1007007⟩
Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
Repisalud
Instituto de Salud Carlos III (ISCIII)
Recercat: Dipósit de la Recerca de Catalunya
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
PLoS Pathogens, Vol 14, Iss 5, p e1007007 (2018)
ISSN: 1553-7366
1553-7374
Popis: Made available in DSpace on 2018-12-11T17:20:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-05-01 Agència de Gestió d’Ajuts Universitaris i de Recerca Secretaría de Estado de Investigación, Desarrollo e Innovación Dirección General de Investigación Científica y Técnica Cryptococcus neoformans is an encapsulated pathogenic yeast that can change the size of the cells during infection. In particular, this process can occur by enlarging the size of the capsule without modifying the size of the cell body, or by increasing the diameter of the cell body, which is normally accompanied by an increase of the capsule too. This last process leads to the formation of cells of an abnormal enlarged size denominated titan cells. Previous works characterized titan cell formation during pulmonary infection but research on this topic has been hampered due to the difficulty to obtain them in vitro. In this work, we describe in vitro conditions (low nutrient, serum supplemented medium at neutral pH) that promote the transition from regular to titan-like cells. Moreover, addition of azide and static incubation of the cultures in a CO2enriched atmosphere favored cellular enlargement. This transition occurred at low cell densities, suggesting that the process was regulated by quorum sensing molecules and it was independent of the cryptococcal serotype/species. Transition to titan-like cell was impaired by pharmacological inhibition of PKC signaling pathway. Analysis of the gene expression profile during the transition to titan-like cells showed overexpression of enzymes involved in carbohydrate metabolism, as well as proteins from the coatomer complex, and related to iron metabolism. Indeed, we observed that iron limitation also induced the formation of titan cells. Our gene expression analysis also revealed other elements involved in titan cell formation, such as calnexin, whose absence resulted in appearance of abnormal large cells even in regular rich media. In summary, our work provides a new alternative method to investigate titan cell formation devoid the bioethical problems that involve animal experimentation. Mycology Reference Laboratory National Centre for Microbiology Instituto de Salud Carlos III, Majadahonda Universidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas Câmpus Araraquara Departamento de Análises Clínicas Laboratório de Micologia Clínica Genomics Unit Core Scientific Services Instituto de Salud Carlos III, Majadahonda Institut Pasteur Unité Biologie des ARN des Pathogènes Fongiques Département de Mycologie Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de Barcelona Albert Einstein College of Medicine Universidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas Câmpus Araraquara Departamento de Análises Clínicas Laboratório de Micologia Clínica Agència de Gestió d’Ajuts Universitaris i de Recerca: 2014SGR-4 Secretaría de Estado de Investigación, Desarrollo e Innovación: BFU2014-54591-C2-1-P Dirección General de Investigación Científica y Técnica: BFU2017-82574-P Secretaría de Estado de Investigación, Desarrollo e Innovación: SAF2014-54336-R Dirección General de Investigación Científica y Técnica: SAF2017-86192-R
Databáze: OpenAIRE