Immunoproteomic Approach to Elucidating the Pathogenesis of Cryptococcosis Caused by <i>Cryptococcus gattii</i>

Jobbins, Sarah E.; Hill, Charles; D’Souza-Basseal, Jocelyn M.; Padula, Matthew P.; Herbert, Ben R.; Krockenberger, M. B.

doi:10.1021/pr100028t

Cited by 27 publications

(40 citation statements)

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“…Hsp70 is a phylogenetically conserved chaperone protein whose expression increases in response to temperature variation and environmental stress [61]. The role of this protein as an antigenic target in the context of cryptococcosis has been reported by various studies in both humans (by Rodrigues et al [62]) and animal models in the clinical and subclinical phases (by Jobbins et al [56] and Young et al [55]), thus supporting our findings.…”

Section: Discussionsupporting

confidence: 89%

“…This approach has frequently been used to identify immunogenic proteins and, consequently, new targets to diagnose several diseases [41][42][43][44][45][46][47][48][49][50][51][52][53][54]. Although similar results have been achieved in cryptococcosis using murine [55] and koala models [56], this is the first report in human beings. In addition, the use of sample isolates obtained directly from patients would be very difficult, because they are hard to obtain directly from the brain or lung during infection, and the sample collected would probably not have a sufficient amount of protein for a proteomic approach.…”

Section: Discussionmentioning

confidence: 84%

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Immunoproteomics and Immunoinformatics Analysis of Cryptococcus Gattii : Novel Candidate Antigens for Diagnosis

et al. 2013

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 84%

Immunoproteomics and Immunoinformatics Analysis of Cryptococcus Gattii : Novel Candidate Antigens for Diagnosis

et al. 2013

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“…In contrast, C. gattii infections prevail in regions with tropical and subtropical climates, predominantly affecting immunocompetent hosts (Lazera et al 2005, Jobbins et al 2010. Moreover, C. gattii has been linked to human and animal outbreaks and has been isolated in countries of temperate climate, demonstrating that the fungus can adapt to new or formerly unknown environments , Byrnes & Heitman 2009, Dixit et al 2009).…”

mentioning

confidence: 99%

Genotypes of Cryptococcus neoformans and Cryptococcus gattii as agents of endemic cryptococcosis in Teresina, Piauí (northeastern Brazil)

Martins

Wanke

Lazéra

et al. 2011

Mem. Inst. Oswaldo Cruz

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“…Gels were then fixed for 30 min in 40% methanol plus 10% acetic acid and stained with Bio-Safe Coomassie stain (Bio-Rad Laboratories). Lanes containing proteins were excised from the stained gels, finely diced into approximately 1-mm-by-1-mm pieces, and then subjected to trypsin in-gel digestion for mass spectrometry, as previously described (19).…”

Section: Methodsmentioning

confidence: 99%

Cryptococcus Strains with Different Pathogenic Potentials Have Diverse Protein Secretomes

et al. 2015

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bSecreted proteins are the frontline between the host and pathogen. In mammalian hosts, secreted proteins enable invasive infection and can modulate the host immune response. Cryptococcosis, caused by pathogenic Cryptococcus species, begins when inhaled infectious propagules establish to produce pulmonary infection, which, if not resolved, can disseminate to the central nervous system to cause meningoencephalitis. Strains of Cryptococcus species differ in their capacity to cause disease, and the mechanisms underlying this are not well understood. To investigate the role of secreted proteins in disease, we determined the secretome for three genome strains of Cryptococcus species, including a hypovirulent and a hypervirulent strain of C. gattii and a virulent strain of C. neoformans. Sixty-seven unique proteins were identified, with different numbers and types of proteins secreted by each strain. The secretomes of the virulent strains were largely limited to proteolytic and hydrolytic enzymes, while the hypovirulent strain had a diverse secretome, including non-conventionally secreted canonical cytosolic and immunogenic proteins that have been implicated in virulence. The hypovirulent strain cannot establish pulmonary infection in a mouse model, but strains of this genotype have caused human meningitis. To directly test brain infection, we used intracranial inoculation and found that the hypovirulent strain was substantially more invasive than its hypervirulent counterpart. We suggest that immunogenic proteins secreted by this strain invoke a host response that limits pulmonary infection but that there can be invasive growth and damage if infection reaches the brain. Given their known role in virulence, it is possible that non-conventionally secreted proteins mediate this process. P rotein secretion is an essential process for all cells. Secretion has roles in various aspects of cell physiology and lifestyle, including nutrient acquisition, cell wall remodeling, signaling, quorum sensing, and defense against other organisms (1). For pathogenic organisms, the secretion of specific proteins can be key to disease progression, allowing the pathogen both to invade and obtain nutrients and to directly modulate the host organism's immune response.The ability to secrete proteins is of particular importance to fungal organisms. Fungi use exodigestion and absorptive nutrition to acquire nutrients and have evolved a complex suite of secreted proteins to degrade the diverse biopolymers encountered in the host or abiotic environment. Comparisons of characterized fungal secretomes suggest that their basal secretome consists of a core set of degradation enzymes. These include polysaccharideactive enzymes, including glycoside hydrolases, carbohydrate esterases, and polysaccharide lyases, which can degrade the major components of plant cell walls such as cellulose and pectin (2). Other degradative enzymes include proteases, for example, secreted aspartyl proteases (SAPs), which have been associated with pathogenicity in the human ...

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Immunoproteomic Approach to Elucidating the Pathogenesis of Cryptococcosis Caused by Cryptococcus gattii

Cited by 27 publications

References 73 publications

Immunoproteomics and Immunoinformatics Analysis of Cryptococcus Gattii : Novel Candidate Antigens for Diagnosis

Immunoproteomics and Immunoinformatics Analysis of Cryptococcus Gattii : Novel Candidate Antigens for Diagnosis

Genotypes of Cryptococcus neoformans and Cryptococcus gattii as agents of endemic cryptococcosis in Teresina, Piauí (northeastern Brazil)

Cryptococcus Strains with Different Pathogenic Potentials Have Diverse Protein Secretomes

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