Candida AND defence

Galleria mellonella cationic protein 8 (GmCP8) is a hemolymph protein previously identified as an opsonin and an inhibitor of fungal proteases. In this work, we showed its bactericidal activity toward Pseudomonas entomophila, Pseudomonas aeruginosa, Bacillus thuringiensis, Staphylococcus aureus, and Escherichia coli and against yeast-like fungi Candida albicans. The activity against E. coli was correlated with bacterial membrane permeabilization. In turn, in the case of P. entomophila, B. thuringiensis, and C...

Vulvovaginal candidiasis (VVC) is a prevalent gynaecological disease characterised by vaginal wall inflammation that is caused by Candida species. VVC impacts almost three-quarters of all women throughout their reproductive years. As the vaginal mucosa is the first point of contact with microbes, vaginal epithelial cells are the first line of defence against opportunistic Candida infection by providing a physical barrier and mounting immunological responses. The mechanisms of defence against this infection are displayed through the rapid shedding of epithelial cells, the presence of pattern recognition receptors, and the release of inflammatory cytokines...

Vaginosis is a condition experienced by most women at least once in their lifetime. This condition arises due to the imbalance in the microbiome of the vaginal ecosystem. Most of the pathogens of this disease are organisms which are commonly found in a normal healthy vagina. The vaginal microbiome is important as they act as a primary defence against secondary infections and Sexually transmitted diseases and infections (STDs and STIs). The vagina is mostly dominated by Lactobacillus along with other microbes including Gardnerella vaginalis, Atopobium vaginae...

Candida albicans is a commensal opportunistic yeast, which is capable of colonising many segments of the human digestive tract. Excessive C. albicans overgrowth in the gut is associated with multiple risk factors such as immunosuppression, antibiotic treatment associated with changes to the gut microbiota and digestive mucosa that support C. albicans translocation across the digestive intestinal barrier and haematogenous dissemination, leading to invasive fungal infections. The C. albicans cell wall contains mannoproteins, β-glucans, and chitin, which are known to trigger a wide range of host cell activities and to circulate in the blood during fungal infection...

Candida infections constitute a blind spot in global public health as very few new anti-fungal drugs are being developed. Genetic surveys of host susceptibilities to such infections using mammalian models have certain disadvantages in that obtaining results is time-consuming, owing to relatively long lifespans, and these results have low statistical resolution because sample sizes are usually small. Here, we report a targeted genetic screening of 5698 RNAi lines encompassing 4135 Drosophila genes with human homologues, several of which we identify as important for host survival after Candida albicans infection...

Cells are constantly challenged by internal or external genotoxic assaults, which may induce a high frequency of DNA lesions, leading to genome instability. Accumulation of damaged DNA is severe or even lethal to cells and can result in abnormal proliferation that can cause cancer in multicellular organisms, aging or cell death. Eukaryotic cells have evolved a comprehensive defence system termed the DNA damage response (DDR) to monitor and remove lesions in their DNA. The DDR has been extensively studied in the budding yeast Saccharomyces cerevisiae ...

Outbreaks associated with Candida auris has notably increased around the globe. Being newly discovered, the evolutionary characteristics of this fungus are unexplored. The crucial feature associated with this pathogen is its multidrug resistance against the available antifungals, which renders a crucial need for developing novel therapeutic strategies. Activation of the antioxidant defence system has been reported as a common mechanism used by pathogens to escape drug toxicity. This system has also recently been recognized as an emerging antifungal drug target...

Neutrophils are the most abundant leukocytes in circulation playing a key role in acute inflammation during microbial infections. Phagocytosis, one of the crucial defence mechanisms of neutrophils against pathogens, is amplified by chemotactic leukotriene (LT)B4 , which is biosynthesized via 5-lipoxygenase (5-LOX). However, extensive liberation of LTB4 can be destructive by over-intensifying the inflammatory process. While enzymatic biosynthesis of LTB4 is well characterized, less is known about molecular mechanisms that activate 5-LOX and lead to LTB4 formation during host-pathogen interactions...

Circulatory inflammatory proteins play a significant role in anti- Candida host immune defence. However, little is known about the genetic variation that contributes to the variability of inflammatory responses in response to C. albicans . To systematically characterize inflammatory responses in Candida infection, we profiled 91 circulatory inflammatory proteins in peripheral blood mononuclear cells (PBMCs) stimulated with C. albicans yeast isolated from 378 individuals of European origin from the 500 Functional Genomics (500FG) cohort of the Human Functional Genomics Project (HFGP) and Lifelines Deep cohort...

The use of probiotics in critically ill adult and children patients has been growing exponentially over the last 20 years. Numerous factors in pediatriac intensive care unit (PICU) patients may contribute to intestinal dysbiosis, which subsequently promotes the pathobiota's growth. Currently, lactobacillus and bifidobacterium species are mainly used to prevent the development of systemic diseases due to the subverted microbiome, followed by streptococcus , enterococcus , propionibacterium , bacillus and Escherichia coli , Lactobacillus rhamnosus GG , and Lactobacillus reuteri DSM 17938 ...

Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans . The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetic patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. This work aimed to review various virulence factors that facilitate the survival of pathogenic C...

Smoking and Candida albicans (C. albicans) infection are risk factors for many oral diseases. Several studies have reported a close relationship between smoking and the occurrence of C. albicans infection. However, the exact underlying mechanism of this relationship remains unclear. We established a rat infection model and a C. albicans-Leuk1 epithelial cell co-culture model with and without smoke exposure to investigate the mechanism by which smoking contributes to C. albicans infection. Oral mucosa samples from healthy individuals and patients with oral leucoplakia were also analysed according to their smoking status...

Candida species are highly adaptable to environmental changes with their phenotypic flexibility allowing for the evasion of most host defence mechanisms. Moreover, increasing resistance of human pathogenic Candida strains has been reported against all four classes of available antifungal drugs, which highlights the need for combinational therapies. Tyrocidines are cyclic antimicrobial peptides that have shown synergistic activity with antifungal drugs such as caspofungin and amphotericin B. However, these cyclodecapeptides have haemolytic activity and cytotoxicity, but they have been used for decades in the clinic for topical applications...

Fungi cause disease in nearly one billion individuals worldwide. Only three classes of antifungal agents are currently available in mainstream clinical use. Emerging and drug-resistant fungi, toxicity, and drug-drug interactions compromise their efficacy and applicability. Consequently, new and improved antifungal therapies are urgently needed. In response to that need, we have developed NP339, a 2-kDa polyarginine peptide that is active against pathogenic fungi from the genera Candida , Aspergillus, and Cryptococcus, as well as others...

Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C...

Vitamin D deficiency remains a global concern. This 'sunshine' vitamin is converted through a multistep process to active 1,25-dihydroxyvitamin D3 (1,25D), the final step of which can occur in macrophages. Here we demonstrate a role for vitamin D in innate immunity. The expression of the complement receptor immunoglobulin (CRIg), which plays an important role in innate immunity, is upregulated by 1,25D in human macrophages. Monocytes cultured in 1,25D differentiated into macrophages displaying increased CRIg mRNA, protein and cell surface expression but not in classical complement receptors, CR3 and CR4...

Therapeutic options to treat invasive fungal infections are still limited. This makes the development of novel antifungal agents highly desirable. Naturally occurring antifungal peptides represent valid candidates, since they are not harmful for human cells and are endowed with a wide range of activities and their mechanism of action is different from that of conventional antifungal drugs. Here, we characterized for the first time the antifungal properties of novel peptides identified in human apolipoprotein B...

Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C...

Invasive fungal diseases represent an unmet clinical need that could benefit from novel immunotherapeutic approaches. Host pattern recognition receptors (e.g., Toll-like receptors, C-type lectins, or scavenger receptors) that sense conserved fungal cell wall constituents may provide suitable immunotherapeutic antifungal agents. Thus, we explored the therapeutic potential of the lymphocyte class I scavenger receptor CD5, a nonredundant component of the antifungal host immune response that binds to fungal β-glucans...

Candida auris is among the most important emerging fungal pathogens, yet mechanistic insights into its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune-cell profiling to uncover innate defence mechanisms against C. auris. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared with Candida albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through the recognition of C-type lectin receptors, mainly elicited by structurally unique C...