Polysaccharide diversity in VNI isolates of Cryptococcus neoformans from Roraima,Northern Brazil |
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| Institution: | 1. Programa de Pós-Graduação em Biologia Parasitária, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil;2. Instituto Carlos Chagas, Fiocruz, Curitiba, Brazil;3. Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;4. Laboratório de Micologia Médica, Instituto de Medicina Tropical, Universidade de São Paulo (USP), São Paulo, Brazil;5. Laboratório de Micologia, Centro de Estudos da Biodiversidade, Universidade Federal de Roraima (UFRR), Roraima, Brazil;6. Hospital Central da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, Brazil;7. Instituto de Microbiologia Paulo de Góes (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil;1. Department of Internal Medicine and Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA;1. Laboratory of Biochemistry, Division of Life Sciences, Korea University, Seoul, 02841, Republic of Korea;2. HAEL Lab, TechnoComplex, Korea University, 145, Seoul, 02841, Republic of Korea;1. Delft University of Technology, Department of Biotechnology, Van der Maasweg 9, 2629HZ, Delft, the Netherlands;2. University of Campinas, School of Chemical Engineering, Av. Albert Einstein, 500, Campinas, Brazil;3. University of Limerick, Bernal Institute, V94 T9PX, Limerick, Ireland;4. Federal University of São Paulo, Institute of Science and Technology, Av. Cesare Mansueto Giulio Lattes, 1201, S. J. Campos, Brazil;1. Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;2. Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran;3. Health Science Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran;4. Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States;5. Center of Expertise in Microbiology, Infection Biology, and Antimicrobial Pharmacology, Tehran, Iran;6. Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran;7. Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;1. Mycology Laboratory, National Institute of Infectious Diseases Evandro Chagas (INI), Fiocruz, Rio de Janeiro, Brazil;2. Laboratory of Clinical Research on Dermatozoonosis in Domestic Animals, National Institute of Infectious Diseases Evandro Chagas (INI), FIOCRUZ, Rio de Janeiro, Brazil;3. Molecular Mycology Research Laboratory, Westmead Institute for Medical Research, Sydney, NSW, Australia |
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| Abstract: | Species of the Cryptococcus genus comprise environmental, encapsulated fungal pathogens that cause lethal meningitis in immunosuppressed individuals. In humans, fungal uptake of hypocapsular Cryptococcus by macrophages was associated with high fungal burden in the cerebrospinal fluid and long-term patient survival. On the basis of the key role of the cryptococcal capsule in disease, we analyzed the diversity of capsular structures in 23 isolates from pigeon excreta collected in the cities of Boa Vista, Bonfim and Pacaraima, in the state of Roraima (Northern Brazil). All isolates were identified as Cryptococcus neoformans (VNI genotype) by MALDI-TOF mass spectrometry. Through a combination of fluorescence microscopy, flow cytometry, ELISA and spectrophotometric methods, each isolate was characterized at the phenotypical level, which included measurements of growth rates at 30 and 37 °C, pigmentation, cell body size, capsular dimensions, serological reactivity, urease production and ability to produce extracellular glucuronoxylomannan (GXM), the main capsular component of C. neoformans. With the exception of melanization, a formidable diversity was observed considering all parameters tested in our study. Of note, hyper and hypo producers of GXM were identified, in addition to isolates with hyper and hypo profiles of reactivity with a polysaccharide-binding monoclonal antibody. Capsular dimensions were also highly variable in the collection of isolates. Extracellular GXM production correlated positively with capsular dimensions, urease activity and cell size. Unexpectedly, GXM concentrations did not correlate with serological reactivity with the cryptococcal capsule. These results reveal a high diversity in the ability of environmental C. neoformans to produce capsular components, which might impact the outcome of human cryptococcosis. |
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| Keywords: | Capsule Cryptococcal diversity Glucuronoxylomannan Glycan heterogeneity |
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