scholarly journals A small molecule produced by Lactobacillus species blocks Candida albicans filamentation by inhibiting a DYRK1-family kinase

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jessie MacAlpine ◽  
Martin Daniel-Ivad ◽  
Zhongle Liu ◽  
Junko Yano ◽  
Nicole M. Revie ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Small Molecule ◽  
Biochemical Characterization ◽  
Opportunistic Pathogen ◽  
Vaginal Candidiasis ◽  
Lactobacillus Species ◽  
Microbiome Composition ◽  
Human Host ◽  
Bioassay Guided Fractionation ◽  
Human Mucosa

AbstractThe fungus Candida albicans is an opportunistic pathogen that can exploit imbalances in microbiome composition to invade its human host, causing pathologies ranging from vaginal candidiasis to fungal sepsis. Bacteria of the genus Lactobacillus are colonizers of human mucosa and can produce compounds with bioactivity against C. albicans. Here, we show that some Lactobacillus species produce a small molecule under laboratory conditions that blocks the C. albicans yeast-to-filament transition, an important virulence trait. It remains unexplored whether the compound is produced in the context of the human host. Bioassay-guided fractionation of Lactobacillus-conditioned medium linked this activity to 1-acetyl-β-carboline (1-ABC). We use genetic approaches to show that filamentation inhibition by 1-ABC requires Yak1, a DYRK1-family kinase. Additional biochemical characterization of structurally related 1-ethoxycarbonyl-β-carboline confirms that it inhibits Yak1 and blocks C. albicans biofilm formation. Thus, our findings reveal Lactobacillus-produced 1-ABC can prevent the yeast-to-filament transition in C. albicans through inhibition of Yak1.

scholarly journals Anticandidal Activities by Lactobacillus Species: An Update on Mechanisms of Action

2021 ◽  
Vol 2 ◽  
Author(s):  
Roberto Vazquez-Munoz ◽  
Anna Dongari-Bagtzoglou
Keyword(s):  
Candida Albicans ◽  
Fungal Infection ◽  
Host Defense ◽  
Defense Mechanisms ◽  
Current Knowledge ◽  
Opportunistic Pathogen ◽  
Mechanisms Of Action ◽  
Lactobacillus Species ◽  
Antifungal Activities

Lactobacilli are among the most studied bacteria in the microbiome of the orodigestive and genitourinary tracts. As probiotics, lactobacilli may provide various benefits to the host. These benefits include regulating the composition of the resident microbiota, preventing – or even potentially reverting- a dysbiotic state. Candida albicans is an opportunistic pathogen that can influence and be influenced by other members of the mucosal microbiota and, under immune-compromising conditions, can cause disease. Lactobacillus and Candida species can colonize the same mucosal sites; however, certain Lactobacillus species display antifungal activities that can contribute to low Candida burdens and prevent fungal infection. Lactobacilli can produce metabolites with direct anticandidal function or enhance the host defense mechanisms against fungi. Most of the Lactobacillus spp. anticandidal mechanisms of action remain underexplored. This work aims to comprehensively review and provide an update on the current knowledge regarding these anticandidal mechanisms.

scholarly journals A GDPase/UDPase Bifunctional Enzyme From Candida Albicans: Purification and Biochemical Characterization

2021 ◽  
Author(s):  
Jaime Alberto Bibián-García ◽  
Jorge Armando Ortiz-Ramírez ◽  
Lilia Maritza Almanza-Villegas ◽  
Ma. del Carmen Cano-Canchola ◽  
Mayra Cuéllar-Cruz ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Protein Separation ◽  
Biochemical Characterization ◽  
Opportunistic Pathogen ◽  
Protein Glycosylation ◽  
Host Cells ◽  
Cell Surface Antigens ◽  
Human Fungal Pathogen ◽  
Double Function ◽  
Systemic Infections

Abstract The most frequently isolated human fungal pathogen is Candida albicans which is responsible for about 50% of all Candida infections. In healthy individuals, this organism resides as a part of the normal microbiota in equilibrium with the host. However, under certain conditions, particularly in immunocompromised patients, this opportunistic pathogen adheres to host cells causing serious systemic infections. Thus, much effort has been dedicated to the study of its physiology with emphasis on factors associated to pathogenicity. A representative analysis deals with the mechanisms of glycoprotein assembly as many cell surface antigens and other macromolecules that modulate the immune system fall within this chemical category. In this regard, studies of the terminal protein glycosylation stage which occurs in Golgi vesicles has led to the identification of nucleotidases that convert glycosyltransferase-generated dinucleotides into the corresponding mononucleotides, thus playing a double function: their activity prevent inhibition of further glycosyl transfer by the accumulation of dinucleotides and the resulting mononucleotides are exchanged by specific membrane transporters for equimolecular amounts of sugar donors from the cytosol. Here, using a simple protocol for protein separation we isolated a bifunctional nucleotidase from C. albicans active on GDP and UDP that was characterized in terms of its molecular mass, response to bivalent ions and other factors, substrate specificity and affinity. Results are discussed in terms of the similarities and differences of this nucleotidase with similar counterparts from other organisms thus contributing to the knowledge of a bifunctional diphosphatase not described before in C. albicans.

scholarly journals Oral Administration of Lactobacillus helveticus LA401 and Lactobacillus gasseri LA806 Combination Attenuates Oesophageal and Gastrointestinal Candidiasis and Consequent Gut Inflammation in Mice

2021 ◽  
Vol 7 (1) ◽  
pp. 57
Author(s):  
Hélène Authier ◽  
Marie Salon ◽  
Mouna Rahabi ◽  
Bénédicte Bertrand ◽  
Claude Blondeau ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Oral Administration ◽  
Mannose Receptor ◽  
Opportunistic Pathogen ◽  
Protective Role ◽  
Lactobacillus Helveticus ◽  
Lectin Receptors ◽  
Lactobacillus Gasseri ◽  
Inflammatory Status ◽  
Gastrointestinal Candidiasis

Candida albicans is an opportunistic pathogen that causes mucosal gastrointestinal (GI) candidiasis tightly associated with gut inflammatory status. The emergence of drug resistance, the side effects of currently available antifungals and the high frequency of recurrent candidiasis indicate that new and improved therapeutics are needed. Probiotics have been suggested as a useful alternative for the management of candidiasis. We demonstrated that oral administration of Lactobacillus gasseri LA806 alone or combined with Lactobacillus helveticus LA401 in Candida albicans-infected mice decrease the Candida colonization of the oesophageal and GI tract, highlighting a protective role for these strains in C. albicans colonization. Interestingly, the probiotic combination significantly modulates the composition of gut microbiota towards a protective profile and consequently dampens inflammatory and oxidative status in the colon. Moreover, we showed that L. helveticus LA401 and/or L. gasseri LA806 orient macrophages towards a fungicidal phenotype characterized by a C-type lectin receptors signature composed of Dectin-1 and Mannose receptor. Our findings suggest that the use of the LA401 and LA806 combination might be a promising strategy to manage GI candidiasis and the inflammation it causes by inducing the intrinsic antifungal activities of macrophages. Thus, the probiotic combination is a good candidate for managing GI candidiasis by inducing fungicidal functions in macrophages while preserving the GI integrity by modulating the microbiota and inflammation.

Interaction of Candida albicans with genital mucosa: effect of sex hormones on adherence of yeasts in vitro

1988 ◽  
Vol 34 (3) ◽  
pp. 224-228 ◽  
Author(s):  
Aliza Kalo ◽  
Esther Segal
Keyword(s):  
Candida Albicans ◽  
Hela Cell ◽  
Sex Hormones ◽  
Hela Cells ◽  
Cell Types ◽  
Vaginal Candidiasis ◽  
Genital Mucosa ◽  
Hela Cell Lines ◽  
I Cells

Findings from our previous studies revealed a correlation between the level of adherence in vitro of Candida albicans to human exfoliated vaginal epithelial cells (VEC) and the hormonal status of the cell donors. In the present study we investigated the effect of the sex hormones estradiol, estriol, progesterone, and testosterone on the binding of the yeasts to HeLa cell lines and VEC in vitro. Monolayers of HeLa cells were exposed to the hormones and yeasts under controlled conditions. The number of adherent yeasts per square millimetre of HeLa cell monolayers and the percentage of VEC with adherent yeasts was estimated by microscopic counts. The results showed that the tested sex hormones affected at various degrees the adhesion of yeasts to HeLa cells or VEC. Progesterone had the most marked effect, leading to a significant increase in the number of adherent yeasts to HeLa cells or in the percentage of adhesion of VEC. In addition, VEC were separated on Percoll gradients into the two cell types: superficial (S) and intermediate (I), cell types which appear physiologically under increased serum levels of estradiol or progesterone, respectively. Adhesion assays with the separated cell populations revealed an increased binding capacity of the I cells. The finding that progesterone increased the adherence of yeasts to genital mucosa and that VEC of the I type have a higher capacity to adhere the yeasts is compatible with our previous observation that increased numbers of I cells, appearing under high level of progesterone, are found in situations known to have predisposition to vaginal candidiasis. Thus, our data point to a possible involvement of the hormone progesterone in the adherence of C. albicans to genital epithelium.

scholarly journals Investigating the Transcriptome of Candida albicans in a Dual-Species Staphylococcus aureus Biofilm Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Bryn Short ◽  
Christopher Delaney ◽  
Emily McKloud ◽  
Jason L. Brown ◽  
Ryan Kean ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Biofilm Formation ◽  
Driving Forces ◽  
Transcriptional Profiling ◽  
Specific Interaction ◽  
Opportunistic Pathogen ◽  
Virulence Proteins ◽  
Biofilm Model ◽  
Upregulated Genes

Candida albicans is an opportunistic pathogen found throughout multiple body sites and is frequently co-isolated from infections of the respiratory tract and oral cavity with Staphylococcus aureus. Herein we present the first report of the effects that S. aureus elicits on the C. albicans transcriptome. Dual-species biofilms containing S. aureus and C. albicans mutants defective in ALS3 or ECE1 were optimised and characterised, followed by transcriptional profiling of C. albicans by RNA-sequencing (RNA-seq). Altered phenotypes in C. albicans mutants revealed specific interaction profiles between fungus and bacteria. The major adhesion and virulence proteins Als3 and Ece1, respectively, were found to have substantial effects on the Candida transcriptome in early and mature biofilms. Despite this, deletion of ECE1 did not adversely affect biofilm formation or the ability of S. aureus to interact with C. albicans hyphae. Upregulated genes in dual-species biofilms corresponded to multiple gene ontology terms, including those attributed to virulence, biofilm formation and protein binding such as ACE2 and multiple heat-shock protein genes. This shows that S. aureus pushes C. albicans towards a more virulent genotype, helping us to understand the driving forces behind the increased severity of C. albicans-S. aureus infections.

scholarly journals Bifidobacterium adolescentis shows potential to strengthen host defence against gastrointestinal infection via inhibition of the opportunistic pathogen Candida albicans and stimulation of human-isolated macrophages killing capacity in vitro

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Liviana Ricci ◽  
Joanna Mackie ◽  
Megan D. Lenardon ◽  
Caitlin Jukes ◽  
Ahmed N. Hegazy ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Bacterial Species ◽  
Opportunistic Pathogen ◽  
Limited Information ◽  
Human Gut ◽  
Bifidobacterium Adolescentis ◽  
Host Immune Responses ◽  
Opportunistic Fungal Pathogen ◽  
Antimicrobial Metabolites

The human gut microbiota enhances the host’s resistance to enteric pathogens via colonisation resistance, a phenomenon that is driven by multiple mechanisms, such as production of antimicrobial metabolites and activation of host immune responses. However, there is limited information on how individual gut bacterial species, particularly many of the dominant anaerobes, might impact the host’s defence. This study investigated the potential of specific human gut isolates to bolster the host’s resistance to infection. First, by antagonising the opportunistic fungal pathogen Candida albicans, and secondly, by modulating the killing capacity of human-isolated macrophages in vitro. Co-culturing C. albicans with faecal microbiota from different healthy individuals revealed varying levels of fungal inhibition. In vitro assays with a panel of representative human gut anaerobes confirmed that culture supernatants from certain bacterial isolates, in particular of Bifidobacterium adolescentis, significantly inhibited C. albicans growth. Mechanistic studies revealed that microbial fermentation acids including acetate and lactate, in combination with the associated decrease in pH, were strong drivers of this inhibitory activity. In the second in vitro assay, human-isolated macrophages were exposed to bacterial supernatants, and subsequently tested for their capacity to eliminate adherent-invasive Escherichia coli. Among the gut anaerobes tested, B. adolescentis was revealed to exert the strongest immunostimulatory and killing effect when compared to the unstimulated macrophages control. B. adolescentis is known to be stimulated by dietary consumption of resistant starch andmay therefore represent an attractive target for the development of probiotic and prebiotic interventions tailored to enhancethe host’s natural defences against infection.

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