Dataset Information

Classical virulence factors do not define Cryptococcus pathogenic diversity

ABSTRACT: Pathogenic determinants in the Cryptococcus genus have been extensively studied, often using standard laboratory isolates. Here, we analyzed the virulence of ten Cryptococcus isolates from diverse sources, species, and genotypes. These isolates exhibited marked differences in their ability to colonize and kill the invertebrate host Galleria mellonella, as well as in their interactions with hemocytes. Capsule formation also varied widely among isolates, with no clear correlation between virulence in G. mellonella and source of isolation, species, fungal burden, capsule size, or interaction with larval hemocytes. To further investigate the basis of this pathogenic diversity, we selected two hypervirulent isolates (C. deuterogattii and C. neoformans) and two hypovirulent isolates (C. gattii and C. neoformans) for in-depth analysis. Differences in the induction of antimicrobial peptides during infection did not account for the observed variation in virulence. Genomic analysis of capsule- related genes, scanning electron microscopy of capsule morphology in vitro and in vivo, and nuclear magnetic resonance of the major capsular polysaccharide all revealed high variability among isolates, but none of these features correlated with virulence. Proteomic profiling of cellular extracts showed that virulent strains were enriched in proteins associated with oxidative processes. Supplementation with an antioxidant during infection increased the virulence of hypovirulent isolates in G. mellonella. These results reveal a high pathogenic diversity in Cryptococcus that goes beyond its classical virulence factors.

INSTRUMENT(S):

ORGANISM(S): Cryptococcus Neoformans Var. Neoformans Jec21 Cryptococcus Gattii Vgii R265

SUBMITTER: Marlon D M Santos

LAB HEAD: Marcio L. Rodrigues

PROVIDER: PXD065863 | Pride | 2025-10-20

REPOSITORIES: Pride

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			Action	DRS
	20231214_189723_BIANCA_49_1.raw	Raw
	20231214_189723_BIANCA_49_2.raw	Raw
	20231214_189823_BIANCA_50_1.raw	Raw
	20231214_189823_BIANCA_50_2.raw	Raw
	20231214_189923_BIANCA_51_1.raw	Raw

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Publications

Pathogenic diversity of Cryptococcus in Galleria mellonella extends beyond classical virulence factors.

Sena Bianca A G BAG Santos Marlon D M MDM Souza Cassia M CM Camillo-Andrade Amanda C AC de Oliveira Haroldo C HC Dos Reis Flavia C G FCG Castelli Rafael F RF Kuczera Diogo D Antoniolli Henrique R M HRM Santos Hellen G G HGG Staats Charley C CC Sassaki Guilherme L GL Carvalho Paulo C PC Rodrigues Marcio L ML

Cell surface (Amsterdam, Netherlands) 20250919

Pathogenic determinants in the Cryptococcus genus have been extensively studied, often using standard laboratory isolates. Here, we analyzed the virulence of ten Cryptococcus isolates from diverse sources, species, and genotypes. These isolates exhibited marked differences in their ability to colonize and kill the invertebrate host Galleria mellonella, as well as in their interactions with hemocytes. Capsule formation also varied widely among isolates, with no clear correlat ...[more]

PMID: 41070140

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Project description:Minerals are essential for proper cell function. In infectious processes where both cells of the causative agent and the host itself are involved, competition for their acquisition is necessary. In this context, pathogenic fungi have developed machinery to ensure the acquisition of minerals and at the same time have perfected strategies that protect them from intoxication by excess of them. In eukaryotic cells, minerals are involved both in the respiratory chain and in cellular metabolisms, which in microorganisms are related to the expression of virulence factors, while in the host, they are related to the activation and regulation of the immune system In the activation of phagocytic cells, in addition, the host can regulate the availability of minerals, which has been called nutritional immunity. Cryptococcosis is an opportunistic mycosis, acquired by inhaling fungal propagules present in the environment; it is a potentially fatal infection that affects the lungs and the central nervous system, both in immunosuppressed and immunocompetent people. The infection is caused by two species, namely: Cryptococcus neoformans (var. grubii (serotype A), var. neoformans (serotype D) and a hybrid corresponding to serotype AD) and Cryptococcus gattii (serotypes B and C). These species present phenotypic, genotypic and epidemiological differences, as well as in their geographical distribution. In recent years, mechanisms for the acquisition of iron and copper, among other micronutrients, have been described in C. neoformans, as well as their relationship, both with the expression of genes associated with virulence factors, the interaction with different intracellular signaling pathways. , especially in routes involved in adaptation to environmental changes and stress conditions. The regulation of the acquisition of these minerals is mediated by several signaling pathways, as the Rim 101 pathway in C. neoformans is essential in adapting to the change in pH and is particular to fungal cells. Iron and copper have been related to the induction of virulence through the production of melanin, capsules and the formation of titan cells, as well as enzymes related to oxidation-reduction phenomena and other virulence factors, which can be regulated by the factor of RIM101 transcription, this pathway induces the expression of genes that encode an iron transporter and a permease (SIT1 and CFT1, respectively) and a copper transporter (CTR4). This enables the yeast to survive in the host because it can rapidly transition from a slightly acidic environment in the phagolysosome to a slightly alkaline environment such as cerebrospinal fluid and serum. For mycoses in general, alternative therapies have been proposed, where the regulation of the acquisition of minerals in the tissue environment during the establishment of the mycosis could be a mechanism to control the growth of the fungus. Therefore, the compression of the signaling networks will allow exploring new alternatives for the development of novel antifungal drugs as well as biological biomarkers, both for the diagnosis and for possible combined therapies at the nutritional immunology level that help prevent and anticipate management. Taking these antecedents into account, we consider it important to evaluate the effect of iron and copper in Colombian clinical isolates of C. neoformans for the prediction of new antifungal targets.

Dataset Information

Classical virulence factors do not define Cryptococcus pathogenic diversity

Dataset's files

Publications

Pathogenic diversity of <i>Cryptococcus</i> in <i>Galleria mellonella</i> extends beyond classical virulence factors.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Classical virulence factors do not define Cryptococcus pathogenic diversity

Dataset's files

Publications

Pathogenic diversity of &lt;i&gt;Cryptococcus&lt;/i&gt; in &lt;i&gt;Galleria mellonella&lt;/i&gt; extends beyond classical virulence factors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Pathogenic diversity of <i>Cryptococcus</i> in <i>Galleria mellonella</i> extends beyond classical virulence factors.