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Lectin-Fc(IgG2a) fusion proteins binding to the cell wall of C. albicans cause structural, metabolic, oxidative, and other pleiotropic effects

ABSTRACT: Candida albicans, an opportunist fungal pathogen ranked top among those causing hospital-acquired infections, exhibits diverse virulence factors aiding its survival within the human body. The rise of multidrug resistance (MDR) in C. albicans requires urgent development of new alternative antifungal therapies. Through genetic engineering gene fusion technologies, our group developed Lectin- Fc(IgG2a) proteins (WGA-Fc(IgG) and Dectin-1-Fc(IgG)) exhibiting antifungal effects against various endemic mycosis and consisting of promising options to combat fungal infections. This study explores the direct impact of Lectin-Fc treatments on C. albicans, shedding light on potential mechanisms disrupting fungal survival and growth. Our results revealed Lectin-Fc(IgG2a) proteins' ability to reduce key polysaccharides on the fungal cell wall. Co-incubations also resulted in oxidative stress in the fungus and alterations in the yeast micronutrient content and lipid reserves. Furthermore, Lectin-Fc(IgG2a) impacted fungal secretion and impeded the release of extracellular vesicles (EVs). The proteomic analysis demonstrated differential protein expression in both the whole C. albicans yeast and EVs post-Lectin-Fc(IgG2a). Notably, these antibody-like structures are slowly degraded by secreted aspartyl proteases (Saps) in vitro, as sap mutants are more prone to growth inhibition. Finally, Lectin-Fc(IgG2a) opsonization enhanced the activation of dendritic cells, contributing to fungal killing. These findings affirm Lectin-Fc(IgG2a) proteins as viable alternatives for therapeutic interventions against fungal infections. Beyond their antibodies-like functions, they induce fungal morphological alterations, and oxidative and metabolic stress, increasing the susceptibility of their cell wall to host immune recognition and elimination.

INSTRUMENT(S):

ORGANISM(S): Candida Albicans (yeast)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Candidiasis

SUBMITTER: Allan Guimaraes

LAB HEAD: Allan Jefferson Guimaraes

PROVIDER: PXD067198 | Pride | 2026-04-06

REPOSITORIES: Pride

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			Action	DRS
	VL_0007202_DIEGO_17_1.raw	Raw
	VL_0007203_DIEGO_17_2.raw	Raw
	VL_0007204_DIEGO_17_3.raw	Raw
	VL_0007206_DIEGO_18_1_200313024537.raw	Raw
	VL_0007207_DIEGO_18_2.raw	Raw

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Project description:Candida albicans is the major invasive fungal pathogen of humans, causing diseases ranging from superficial mucosal infections to disseminated, systemic infections which are often life threatening. Hematogenously disseminated candidiasis (HDC) has a 47% mortality rate despite current antifungal therapy. An increase in prevalence, as well as an increasing resistance to most of the clinically important antifungal therapies, provides a strong impetus to understand the molecular mechanisms of pathogenesis and the acquisition of drug resistance. This information holds promise to identify novel therapeutic targets. A complete and accurate characterization of how the transcriptome of C. albicans responds to its interaction with cells from the host is an absolute necessity to accomplish this goal. RNA-seq (deep-sequencing of cDNA) provides an unbiased method to define comprehensively and systematically the transcriptome of an organism. We propose a comprehensive characterization of the C. albicans transcriptome in two different human tissue culture models, using RNA-seq. Such a characterization will shed unprecedented light on how fungal pathogens sense and respond to the host environment and how the host tissue responds to fungal invasion. We performed a comprehensive characterization of the C. albicans transcriptome in two different murine models of candidiasis (HDC and oropharyngeal candidiasis (OPC)), and two different human tissue culture models, using RNA-seq. Because the two murine models accurately recapitulate the pathology that is observed in clinical cases of candidiasis, we are confident that gene expression levels will provide an accurate representation of what occurs during the course of an infection in humans. Such a characterization of the in vivo transcriptome will shed unprecedented light on how fungal pathogens sense and respond to the host environment and how the host tissue responds to fungal invasion. PRJNA86065 Two different strains of C. albicans (SC5314 or WO-1) were used to infect two different types of human tissue culture monolayers (HUVECs or OKF6-TERT2). RNA from the infection mixtures were harvested at 90 minutes, 5 hours and 8 hours post infection. Experiments were performed in biological duplicate.

Project description:Candida albicans is the major invasive fungal pathogen of humans, causing diseases ranging from superficial mucosal infections to disseminated, systemic infections which are often life threatening. Hematogenously disseminated candidiasis (HDC) has a 47% mortality rate despite current antifungal therapy. An increase in prevalence, as well as an increasing resistance to most of the clinically important antifungal therapies, provides a strong impetus to understand the molecular mechanisms of pathogenesis and the acquisition of drug resistance. This information holds promise to identify novel therapeutic targets. A complete and accurate characterization of how the transcriptome of C. albicans responds to its interaction with cells from the host is an absolute necessity to accomplish this goal. RNA-seq (deep-sequencing of cDNA) provides an unbiased method to define comprehensively and systematically the transcriptome of an organism. We propose a comprehensive characterization of the C. albicans transcriptome in two different human tissue culture models, using RNA-seq. Such a characterization will shed unprecedented light on how fungal pathogens sense and respond to the host environment and how the host tissue responds to fungal invasion. We performed a comprehensive characterization of the C. albicans transcriptome in two different murine models of candidiasis (HDC and oropharyngeal candidiasis (OPC)), and two different human tissue culture models, using RNA-seq. Because the two murine models accurately recapitulate the pathology that is observed in clinical cases of candidiasis, we are confident that gene expression levels will provide an accurate representation of what occurs during the course of an infection in humans. Such a characterization of the in vivo transcriptome will shed unprecedented light on how fungal pathogens sense and respond to the host environment and how the host tissue responds to fungal invasion. PRJNA211732 C. albicans strain SC5314 was used to infect mice in a murine model of systemic candidiasis as well as a murine model of oropharyngeal candidiasis. For the disseminated model, kidneys were harvested at 6 hours, 12 hours, 24 hours and 48 hours after infection. For the oropharyngeal model, tongues were harvest at 1 day, 2 days, 3 days, and 5 days after infection. Total RNA was extracted from all harvested tissues and subject to RNA-seq. We also tested 3 C. albicans mutants in the disseminated model. For the infections with the mutant strains, only 1 timepoint (24 hours post-infection) was analyzed.

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Lectin-Fc(IgG2a) fusion proteins binding to the cell wall of C. albicans cause structural, metabolic, oxidative, and other pleiotropic effects

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