Dataset Information

Proteomic studies on the effects of the deletion of two aminophospholipid translocases in the cellular and extracellular vesicle fractions of Cryptococcus neoformans

ABSTRACT: Flippases are enzymes responsible for the architecture of eukaryotic membranes, regulating various mechanisms of molecular transport and lipid translocation. In Cryptococcus neoformans, a major fungal pathogen, the aminophospholipid translocase 1 (Apt1) flippase plays roles in fungal virulence, membrane architecture, and extracellular vesicle (EV) polysaccharide cargo, among other physiological processes, making this enzyme a potential drug target. The effect of APT1 deletion on the fungal proteome is unknown, limiting the understanding of how this enzyme functions in cryptococcal physiology. The APT gene family includes other members, such as APT2, whose functions in C. neoformans are virtually unknown. In this study, we first investigated the impact of APT1 and APT2 deletion on EV formation in C. neoformans. We found that EV formation was not quantitatively affected by the deletion of APT1 or APT2. As previously observed, the absence of Apt1 resulted in decreased polysaccharide concentration in EVs, but the deletion of APT2 did not affect vesicular polysaccharide concentration. To gain a deeper understanding of how Apt1 and Apt2 influence the physiology of C. neoformans, we then characterized the EV and cellular proteomes of C. neoformans mutants lacking expression of the APT1 and APT2 genes, comparing them to the proteomes of wild-type (WT) cells. Our results show that the deletion of APT1 and APT2 impacts both the cellular and EV proteomes of C. neoformans, with unique elements related to each gene. These findings demonstrate the differential roles of Apt1 and Apt2 in EV formation and suggest their direct involvement in the physiology of C. neoformans. Our results contribute to the understanding of how cryptococcal flippases could be targeted by drugs in the future.

INSTRUMENT(S):

ORGANISM(S): Cryptococcus Neoformans Tu401-mp_1

TISSUE(S): Cell Culture

SUBMITTER: Marlon D M Santos

LAB HEAD: Marcio L. Rodrigues

PROVIDER: PXD056961 | Pride | 2026-06-29

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20231206_184923_Rafael_1_3.raw	Raw
	20231206_184923_Rafael_1_4.raw	Raw
	20231206_185023_Rafael_2_1.raw	Raw
	20231206_185023_Rafael_2_2.raw	Raw
	20231206_185123_Rafael_3_1.raw	Raw

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Publications

The flippases Apt1 and Apt2 differentially influence extracellular vesicle cargo and polysaccharide secretion in Cryptococcus neoformans.

Castelli Rafael F RF de Oliveira Haroldo C HC Santos Marlon D M MDM Camillo-Andrade Amanda C AC Dos Reis Flavia C G FCG Carvalho Paulo C PC Rodrigues Marcio L ML

Journal of proteomics 20250619

In the fungus Cryptococcus neoformans, the aminophospholipid translocase 1 (Apt1) flippase plays roles in virulence, membrane architecture, and extracellular vesicle (EV) polysaccharide cargo. The effect of APT1 deletion on the fungal proteome is unknown, limiting the understanding of its functions in physiology. The APT gene family also includes APT2, whose functions in C. neoformans are virtually unknown. We investigated the impact of APT1 and APT2 deletion on EV formation in C. neoformans. Th ...[more]

PMID: 40543703

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Project description:Fungal diseases impact the lives of millions of people across the globe ranging from superficial to systemic infections. Treatment options toward fungal diseases are limited given the emergence of new pathogens with intrinsic resistance and heightened evolution toward resistant strains. To effectively combat fungal disease, rapid and reliable diagnostic methods are required, including current methodologies using antigen detection, culturing, microscopy, and molecular tools. However, the flexibility of these platforms to diagnose infection using non-invasive methods and predict the outcome of disease are limited. In this study, we apply state-of-the-art mass spectrometry-based proteomics to perform dual perspective (i.e., host and pathogen) profiling of cryptococcal infection. Whole blood collected over a temporal scale following murine model challenged with the human fungal pathogen, Cryptococcus neoformans, revealed detection of >3,000 host proteins and 160 fungal proteins across all samples. From the host perspective, temporal regulation of known immune-associated proteins, including eosinophil peroxidase and lipocalin, along with suppression of lipoproteins, demonstrated infection- and time-dependent host remodeling. Conversely, from the pathogen perspective, known and putative virulence-associated proteins were detected, including proteins associated with fungal extracellular vesicles and host immune modulation. Moreover, we observed and validated a new mechanism of immune system activation by C. neoformans through modulation of haptoglobin. Further, we assessed the predictive power of dual perspective proteome profiling toward prognostics of cryptococcal infection and report a previously undisclosed integration among virulence factor production, immune system modulation, and individual model survival. Together, our findings pose novel biomarkers of cryptococcal infection from whole blood and highlight the potential of personal proteome profiles to determine the prognosis of cryptococcal infection, a new parameter in fungal disease management. his submission includes a partial dataset. Additional RAW files will be added shortly after manuscript publication to complete the full data submission.