Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion

ABSTRACT: Candida albicans is an inhabitant of mucosal surfaces in healthy humans but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG.

ORGANISM(S): Candida albicans

PROVIDER: GSE97755 | GEO | 2017/09/14

SECONDARY ACCESSION(S): PRJNA382820

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Human antibodies enhance association of macrophages to Candida albicans and reduce fungal-mediated epithelial damage

Project description:Candida albicans is a common commensal on human mucosal surfaces, but can become pathogenic, e.g. if the host is immunocompromised. While neutrophils, macrophages and T cells-driven activation of neutrophils are regarded as major players in the defence against C. albicans, the role of B cells and the protective function of their antibodies are less well characterized. In this study, we show that human serum antibodies are able to enhance the the association of human macrophages with C. albicans cells . Human serum antibodies are also capable of reducing the growth of the fungi as well as inhibiting adhesion to epithelial cells. Furthermore, human serum antibodies impair C. albicans’ invasion into human oral epithelial cells by blocking induced endocytosis and consequently host cell damage. While aspartic proteases secreted by C. albicans were able to cleave human IgG, this process does not appear to affect the protective function of human antibodies in adhesion. Thus, humans are equipped with antiC. albicans antibodies, which can enhance antifungal activities and which can prevent fungal mediated epithelial damage (even in immunocompromised settings).

2022-04-04 | PXD026082 | Pride

in vitro ubiquitination by E3 ligase Cbl-b

Project description:Fungal infections claim an estimated 1.5 million lives every year. Mechanisms that protect from fungal infections are still elusive. Recognition of fungal pathogens relies on C-type lectin receptors (CLR) and their downstream signaling kinase SYK. Here we report that the E3-ubiquitin-ligase CBL-B controls proximal C-type lectin receptor signaling in macrophages and dendritic cells. We show that CBL-B associates with SYK and ubiquitinates SYK, Dectin-1, and Dectin-2 upon fungal recognition. Functionally, CBL-B deficiency results in increased inflammasome activation, enhanced reactive oxygen species production, and increased fungal killing. Genetic deletion of Cblb protects mice from morbidity caused by cutaneous infection and markedly improves survival upon a lethal systemic infection with Candida albicans. Based on these findings, we engineered a cell-permeable CBL-B inhibitory peptide that protects mice from lethal C. albicans infections. We thus describe a key role for Cblb in the regulation of innate anti-fungal immunity and establish a novel paradigm for the treatment of fungal sepsis.

2017-03-29 | MSV000080745 | MassIVE

in vitro ubiquitination by E3 ligase Cbl-b

2016-06-17 | PXD004256 | Pride

Iron Chelator Deferasirox Reduces Candida albicans Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis

Project description:Candida albicans, the causative agent of mucosal infections including oropharyngeal candidiasis (OPC) as well as bloodstream infections is becoming increasingly resistant to existing treatment options. In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat off label diseases is a promising strategy. C. albicans requires environmental iron for survival and virulence while host nutritional immunity deploys iron-binding proteins to sequester iron and reduce fungal growth. Here we evaluated the role of iron-limitation using Deferasirox (an FDA approved iron chelator for treatment of patients with iron overload) during murine OPC; and assessed Deferasirox-treated C. albicans for its interaction with human oral epithelial (OE), neutrophils, and antimicrobial peptides. Therapeutic Deferasirox treatment significantly reduced salivary iron levels while a non-significant reduction in fungal burden was observed. Preventive treatment that allowed for two additional days of drug administration in our murine model, resulted in significant reduction of C. albicans colony forming units (CFU)/g of tongue tissue, a significant reduction in salivary iron levels, and significantly reduced neutrophil-mediated inflammation. C. albicans harvested from tongues of animals undergoing preventive treatment had differential expression of 106 genes, including those involved in iron metabolism, adhesion, and response to host innate immunity. Moreover, Deferasirox-treated C. albicans cells had two-fold reduction in survival in neutrophil phagosomes (with greater susceptibility to oxidative stress); and reduced adhesion and invasion of OE cells, in vitro. Thus Deferasirox treatment has the potential to alleviate OPC by affecting C. albicans gene expression and reducing virulence

2018-12-04 | GSE123277 | GEO

Genome-wide transcriptional profiling of human PBMCs stimulated with Candida albicans and non-fungal inflammatory stimuli

2014-05-01 | GSE42606 | GEO

Genome-wide transcriptional profiling of human PBMCs stimulated with Candida albicans and non-fungal inflammatory stimuli

Project description:Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections, but human anti-fungal immunity remains poorly defined. Expression profiling of Candida-stimulated human peripheral blood mononuclear cells (PBMCs) provides new insights into Candida-specific host defense mechanisms in humans. Total RNA was extracted from PBMCs from healthy human volunteers. PBMCs were stimulated with heat-killed Candida albicans (10^6/ml), non-fungal inflammatory stimuli or RPMI control for 4 or 24 hours. A large number of biological replicates (>20) were included per stimulation condition and duration.

2014-05-01 | E-GEOD-42606 | biostudies-arrayexpress

Transcriptional profiling of C. albicans in the presence of mucin versus absence of mucin

Project description:Candida albicans is the most prevalent fungal pathogen of humans, causing a variety of diseases ranging from superficial mucosal infections to deep-seated systemic infections. Mucus, the gel that coats all wet epithelial surfaces, accommodates Candida albicans as part of the regular microbiome where C. albicans resides asymptomatically in healthy humans. Through a series of in vitro experiments combined with genome-wide transcriptional profiling, we show that mucin biopolymers, the main gel-forming constituents of mucus, induce a new oval-shaped morphology in C. albicans in which a range of genes related to adhesion, filamentation, and biofilm formation are down-regulated. We also show that corresponding phenotypes are suppressed, rendering Candida incapable of forming biofilms on a range of different synthetic surfaces and human epithelial cells. Our data suggests that mucins can manipulate Candida physiology and we hypothesize that they are key regulators for retaining Candida in the host-compatible, commensal state.

2014-03-11 | GSE55766 | GEO

Transcriptional profiling of C. albicans in the presence of mucin versus absence of mucin

2014-03-11 | E-GEOD-55766 | biostudies-arrayexpress

RNA abundance in wild-type and rtt109 -/- Candida albicans, with and without peroxide stress

Project description:Candida albicans is a ubiquitous opportunistic pathogen that is the most prevalent cause of hospital-acquired fungal infections. In mammalian hosts, C. albicans is engulfed by phagocytes that attack the pathogen with DNA-damaging reactive oxygen species (ROS). Acetylation of histone H3 lysine 56 (H3K56) by the fungal-specific histone acetyltransferase Rtt109 is important for yeast model organisms to survive DNA damage and maintain genome integrity. To assess the importance of Rtt109 for C. albicans pathogenicity, we deleted the predicted homologue of Rtt109 in the clinical C. albicans isolate, SC5314. C. albicans rtt109 -/- mutant cells lack acetylated H3K56 (H3K56ac) and are hypersensitive to genotoxic agents. Additionally, rtt109 -/- mutant cells constitutively display increased H2A S129 phosphorylation and elevated DNA repair gene expression, consistent with endogenous DNA damage.

2010-01-04 | GSE18936 | GEO

Candida albicans interaction with intestinal epithelial cells

Project description:To characterize the interaction of Candida albicans with intestinal epithelial cells (C2BBe1) from early fungal adhesion to invasion (up to 6 h) and the late translocation and damage phase (12 -24 h), we conducted dual RNA-sequencing of C. albicans-infected C2BBe1 cells over a 24 h time course, with sampling at 0 h, 45 min, 3 h, 6 h, 12 h, and 24 h.

2024-02-07 | GSE237496 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data