Effect of Diglyceryl Dicaprylate on Candida albicans growth and pathogenicity

Author(s):  
Tomojiro Koide ◽  
Muneaki Tamura

Abstract The antifungal effect of diglyceryl dicaprylate (DGDC), one of the emulsifiers used as a food additive, on Candida albicans which is a pathogenic fungus that is predominant in the oral cavity was investigated. This component did not affect C. albicans growth, however, it suppressed some virulence factors in a concentration-dependent manner. Furthermore, the suppression of pathogenic factors, such as biofilm formation, adhesion, highly pathogenic dimorphism, and ability to produce proteolytic enzymes was due to reduction in mRNA expression levels of genes involved in fungal pathogenicities. From these results, this emulsifier could potentially prevent the development of intraoral and extraoral diseases involving C. albicans and could potentially use in oral care and improvement of quality of life.

2001 ◽  
Vol 69 (11) ◽  
pp. 6813-6822 ◽  
Author(s):  
Simon L. Newman ◽  
Angela Holly

ABSTRACT Candida albicans is a component of the normal flora of the alimentary tract and also is found on the mucocutaneous membranes of the healthy host. Candida is the leading cause of invasive fungal disease in premature infants, diabetics, and surgical patients, and of oropharyngeal disease in AIDS patients. As the induction of cell-mediated immunity to Candida is of critical importance in host defense, we sought to determine whether human dendritic cells (DC) could phagocytose and degradeCandida and subsequently present Candidaantigens to T cells. Immature DC obtained by culture of human monocytes in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4 phagocytosed unopsonized Candida in a time-dependent manner, and phagocytosis was not enhanced by opsonization of Candida in serum. Like macrophages (Mφ), DC recognized Candida by the mannose-fucose receptor. Upon ingestion, DC killed Candida as efficiently as human Mφ, and fungicidal activity was not enhanced by the presence of fresh serum. Although phagocytosis ofCandida by DC stimulated the production of superoxide anion, inhibitors of the respiratory burst (or NO production) did not inhibit killing of Candida, even when phagocytosis was blocked by preincubation of DC with cytochalasin D. Further, although apparently only modest phagolysosomal fusion occurred upon DC phagocytosis of Candida, killing ofCandida under anaerobic conditions was almost equivalent to killing under aerobic conditions. Finally, DC stimulatedCandida-specific lymphocyte proliferation in a concentration-dependent manner after phagocytosis of both viable and heat-killed Candida cells. These data suggest that, in vivo, such interactions between DC and C. albicans may facilitate the induction of cell-mediated immunity.


2004 ◽  
Vol 3 (4) ◽  
pp. 919-931 ◽  
Author(s):  
Takuya Miwa ◽  
Yukinobu Takagi ◽  
Makiko Shinozaki ◽  
Cheol-Won Yun ◽  
Wiley A. Schell ◽  
...  

ABSTRACT In response to various extracellular signals, the morphology of the human fungal pathogen Candida albicans switches from yeast to hypha form. Here, we report that GPR1 encoding a putative G-protein-coupled receptor and GPA2 encoding a Gα subunit are required for hypha formation and morphogenesis in C. albicans. Mutants lacking Gpr1 (gpr1/gpr1) or Gpa2 (gpa2/gpa2) are defective in hypha formation and morphogenesis on solid hypha-inducing media. These phenotypic defects in solid cultures are suppressed by exogenously added dibutyryl-cyclic AMP (dibutyryl-cAMP). Biochemical studies also reveal that GPR1 and GPA2 are required for a glucose-dependent increase in cellular cAMP. An epistasis analysis indicates that Gpr1 functions upstream of Gpa2 in the same signaling pathway, and a two-hybrid assay reveals that the carboxyl-terminal tail of Gpr1 interacts with Gpa2. Moreover, expression levels of HWP1 and ECE1, which are cAMP-dependent hypha-specific genes, are reduced in both mutant strains. These findings support a model that Gpr1, as well as Gpa2, regulates hypha formation and morphogenesis in a cAMP-dependent manner. In contrast, GPR1 and GPA2 are not required for hypha formation in liquid fetal bovine serum (FBS) medium. Furthermore, the gpr1 and the gpa2 mutant strains are fully virulent in a mouse infection. These findings suggest that Gpr1 and Gpa2 are involved in the glucose-sensing machinery that regulates morphogenesis and hypha formation in solid media via a cAMP-dependent mechanism, but they are not required for hypha formation in liquid medium or during invasive candidiasis.


Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 816
Author(s):  
Yu Kono ◽  
Muneaki Tamura ◽  
Marni E. Cueno ◽  
Morio Tonogi ◽  
Kenichi Imai

Controlling the oral microbial flora is putatively thought to prevent not only oral diseases, but also systemic diseases caused by oral diseases. This study establishes the antibacterial effect of the novel bioactive substance “S-PRG filler” on oral bacteria. We examined the state of oxidative stress caused by the six types of ions released in eluate from the S-PRG filler in oral bacterial cells. Moreover, we investigated the effects of these ions on the growth and pathogenicity of Gram-positive and Gram-negative bacteria. We found that the released ions affected SOD amount and hydrogen peroxide in bacterial cells insinuating oxidative stress occurrence. In bacterial culture, growth inhibition was observed depending on the ion concentration in the medium. Additionally, released ions suppressed Streptococcus mutans adhesion to hydroxyapatite, S. oralis neuraminidase activity, and Porphyromonas gingivalis hemagglutination and gingipain activity in a concentration-dependent manner. From these results, it was suggested that the ions released from the S-PRG filler may suppress the growth and pathogenicity of the oral bacterial flora. This bioactive material is potentially useful to prevent the onset of diseases inside and outside of the oral cavity, which in turn may have possible applications for oral care and QOL improvement.


2017 ◽  
Vol 474 (17) ◽  
pp. 3027-3043 ◽  
Author(s):  
JiEun Yun ◽  
Jae-Sam Hwang ◽  
Dong Gun Lee

The cockroach, which is a household insect, is an established model organism in research. Periplanetasin-2, derived from the American cockroach Periplaneta americana, exerted potent antifungal effect against pathogenic fungi without causing hemolysis. Periplanetasin-2 induced oxidative stress by generation of reactive oxygen species (ROS) and lipid peroxidation. Periplanetasin-2 also caused apoptosis by exposure of phosphatidylserine and fragmentation of DNA, exerted in a concentration-dependent manner. Hence, we investigated the mitochondrial apoptotic mechanism of periplanetasin-2 in Candida albicans. After treatment with periplanetasin-2, we observed mitochondrial depolarization and calcium accumulation. Moreover, we observed a decrease in cytosolic glutathione, and an increase in mitochondrial glutathione, indicating that periplanetasin-2 induced oxidative stress and high ROS production in the mitochondria. Because of this mitochondrial dysfunction, cytochrome c was released from the mitochondria into the cytosol, and caspase was activated in a time-dependent manner. In summary, the antifungal peptide periplanetasin-2 activates apoptotic signals in the mitochondria by induction of oxidative stress.


mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yang Lu ◽  
Chang Su ◽  
Shatarupa Ray ◽  
Yuncong Yuan ◽  
Haoping Liu

ABSTRACT Candida albicans is the most common cause of invasive fungal infections in humans. Its ability to sense and adapt to changing carbon dioxide levels is crucial for its pathogenesis. Carbon dioxide promotes hyphal development. The hypha-specific transcription factor Ume6 is rapidly degraded in air, but is stable under physiological CO2 and hypoxia to sustain hyphal elongation. Here, we show that Ume6 stability is regulated by two parallel E3 ubiquitin ligases, SCFGrr1 and Ubr1, in response to CO2 and O2, respectively. To uncover the CO2 signaling pathway that regulates Ume6 stability, we performed genetic screens for mutants unable to respond to CO2 for sustained filamentation. We find that the type 2C protein phosphatase Ptc2 is specifically required for CO2-induced stabilization of Ume6 and hyphal elongation. In contrast, the cyclin-dependent kinase Ssn3 is found to be required for Ume6 phosphorylation and degradation in atmospheric CO2. Furthermore, we find that Ssn3 is dephosphorylated in 5% CO2 in a Ptc2-dependent manner, whereas deletion of PTC2 has no effect on Ssn3 phosphorylation in air. Our study uncovers the Ptc2-Ssn3 axis as a new CO2 signaling pathway that controls hyphal elongation by regulating Ume6 stability in C. albicans. IMPORTANCE The capacity to sense and adapt to changing carbon dioxide levels is crucial for all organisms. In fungi, CO2 is a key determinant involved in fundamental biological processes, including growth, morphology, and virulence. In the pathogenic fungus Candida albicans, high CO2 is directly sensed by adenylyl cyclase to promote hyphal growth. However, little is known about the mechanism by which hyphal development is maintained in response to physiological levels of CO2. Here we report that a signal transduction system mediated by a phosphatase-kinase pair controls CO2-responsive Ume6 phosphorylation and stability that in turn dictate hyphal elongation. Our results unravel a new regulatory mechanism of CO2 signaling in fungi.


2009 ◽  
Vol 77 (7) ◽  
pp. 3056-3064 ◽  
Author(s):  
Akiko Miyazato ◽  
Kiwamu Nakamura ◽  
Natsuo Yamamoto ◽  
Héctor M. Mora-Montes ◽  
Misuzu Tanaka ◽  
...  

ABSTRACT The innate immune system of humans recognizes the human pathogenic fungus Candida albicans via sugar polymers present in the cell wall, such as mannan and β-glucan. Here, we examined whether nucleic acids from C. albicans activate dendritic cells. C. albicans DNA induced interleukin-12p40 (IL-12p40) production and CD40 expression by murine bone marrow-derived myeloid dendritic cells (BM-DCs) in a dose-dependent manner. BM-DCs that lacked Toll-like receptor 4 (TLR4), TLR2, and dectin-1, which are pattern recognition receptors for fungal cell wall components, produced IL-12p40 at levels comparable to the levels produced by BM-DCs from wild-type mice, and DNA from a C. albicans pmr1Δ null mutant, which has a gross defect in mannosylation, retained the ability to activate BM-DCs. This stimulatory effect disappeared completely after DNase treatment. In contrast, RNase treatment increased production of the cytokine. A similar reduction in cytokine production was observed when BM-DCs from TLR9−/− and MyD88−/− mice were used. In a luciferase reporter assay, NF-κB activation was detected in TLR9-expressing HEK293T cells stimulated with C. albicans DNA. Confocal microscopic analysis showed similar localization of C. albicans DNA and CpG-oligodeoxynucleotide (CpG-ODN) in BM-DCs. Treatment of C. albicans DNA with methylase did not affect its ability to induce IL-12p40 synthesis, whereas the same treatment completely eliminated the ability of CpG-ODN to induce IL-12p40 synthesis. Finally, impaired clearance of this fungal pathogen was not found in the kidneys of TLR9−/− mice. These results suggested that C. albicans DNA activated BM-DCs through a TLR9-mediated signaling pathway using a mechanism independent of the unmethylated CpG motif.


2011 ◽  
Vol 55 (6) ◽  
pp. 3043-3045 ◽  
Author(s):  
Rana S. Traboulsi ◽  
Pranab K. Mukherjee ◽  
Jyotsna Chandra ◽  
Robert A. Salata ◽  
Richard Jurevic ◽  
...  

ABSTRACTThe effect of gentian violet againstCandida albicansand non-Candida albicansbiofilms formed on polymethylmethacrylate strips was evaluated using a dry weight assay and confocal laser scanning microscopy. The ability of gentian violet to inhibitCandida albicansgermination was also assessed. Gentian violet activity againstCandidabiofilms was demonstrated by a reduction in dry weight, disruption of biofilm architecture, and reduced biofilm thickness. Additionally, gentian violet inhibitedCandidagermination in a concentration-dependent manner.


2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Akihiro Wada ◽  
Keiji Murakami ◽  
Yumi Ishikawa ◽  
Takashi Amoh ◽  
Kouji Hirao ◽  
...  

Periodontitis is a chronic inflammatory disease caused by periodontopathogenic bacteria that form biofilms in periodontal pockets. The gingival epithelium acts as the first physical barrier in fighting attacks by periodontopathogenic pathogens, such as the primary etiological agent Porphyromonas gingivalis, and various exogenous chemicals, as well as regulates the local innate immune responses. Therefore, the development of novel oral care products to inhibit inflammatory reactions caused by bacterial infection and protect the gingival epithelium is necessary. Juncus effusus L. has generally been used as an indigenous medicine, such as a diuretic, an antipyretic, and an analgesic, in ancient practice. In this study, we examined the effects of a water extract from J. effusus L. on the inhibition of the inflammatory reaction elicited by bacterial infection and protection of the oral epithelium by chemical irritation. Pretreatment of oral epithelial cells with the water extract from J. effusus L. significantly reduced P. gingivalis or its lipopolysaccharide- (LPS-) mediated production of chemokines (interleukin-8 and C-C-chemokine ligand20) in a concentration-dependent manner with comparable to or greater effects than epigallocatechin gallate and protected oral epithelial cells from injury by chemical irritants, cetylpyridinium chloride, and benzethonium chloride. Moreover, the water extract from J. effusus L. in the presence of antimicrobial agents or antifibrinolytics already used as ingredients in mouthwash could significantly reduce the production of chemokines from P. gingivalis LPS-stimulated oral epithelial cells in a concentration-dependent manner. These findings suggest that the water extract from J. effusus L. is potentially useful for oral care to prevent oral infections, such as periodontal infections, and maintain oral epithelial function.


2012 ◽  
Vol 78 (7) ◽  
pp. 2190-2199 ◽  
Author(s):  
Sanae A. Ishijima ◽  
Kazumi Hayama ◽  
Jeremy P. Burton ◽  
Gregor Reid ◽  
Masashi Okada ◽  
...  

ABSTRACTOral candidiasis is often accompanied by severe inflammation, resulting in a decline in the quality of life of immunosuppressed individuals and elderly people. To develop a new oral therapeutic option for candidiasis, a nonpathogenic commensal oral probiotic microorganism,Streptococcus salivariusK12, was evaluated for its ability to modulateCandida albicansgrowthin vitro, and its therapeutic activity in an experimental oral candidiasis model was tested.In vitroinhibition of mycelial growth ofC. albicanswas determined by plate assay and fluorescence microscopy. Addition ofS. salivariusK12 to modified RPMI 1640 culture medium inhibited the adherence ofC. albicansto the plastic petri dish in a dose-dependent manner. Preculture ofS. salivariusK12 potentiated its inhibitory activity for adherence ofC. albicans. Interestingly,S. salivariusK12 was not directly fungicidal but appeared to inhibitCandidaadhesion to the substratum by preferentially binding to hyphae rather than yeast. To determine the potentially anti-infective attributes ofS. salivariusK12 in oral candidiasis, the probiotic was administered to mice with orally induced candidiasis. Oral treatment withS. salivariusK12 significantly protected the mice from severe candidiasis. These findings suggest thatS. salivariusK12 may inhibit the process of invasion ofC. albicansinto mucous surfaces or its adhesion to denture acrylic resins by mechanisms not associated with the antimicrobial activity of the bacteriocin.S. salivariusK12 may be useful as a probiotic as a protective tool for oral care, especially with regard to candidiasis.


Materials ◽  
2021 ◽  
Vol 14 (16) ◽  
pp. 4696
Author(s):  
Carmen Gaidau ◽  
Maria Stanca ◽  
Mihaela-Doina Niculescu ◽  
Cosmin-Andrei Alexe ◽  
Marius Becheritu ◽  
...  

The aim of this paper was to select keratin hydrolysate with bioactive properties by using the enzymatic hydrolysis of wool. Different proteolytic enzymes such as Protamex, Esperase, and Valkerase were used to break keratin molecules in light of bioactive additive preparation. The enzymatic keratin hydrolysates were assessed in terms of the physico-chemical characteristics related to the content of dry substance, total nitrogen, keratin, ash, cysteic sulphur, and cysteine. The influence of enzymatic hydrolysis on molecular weight and amino acid composition was determined by gel permeation chromatography (GPC) and gas chromatography-mass spectrometry (GC-MS) analyses. Antimicrobial activity of keratin hydrolysates was analysed against Fusarium spp., a pathogenic fungus that can decrease the quality of plants. The bioactivity of enzymatic hydrolysates was tested on maize plants and allowed us to select the keratin hydrolysates processed with the Esperase and Valkerase enzymes. The ratio of organised structures of hydrolysate peptides was analysed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) deconvolution of the amide I band and may explain the difference in their bioactive behaviour. The most important modifications in the ATR spectra of maize leaves in correlation with the experimentally proven performance on maize development by plant length and chlorophyll index quantification were detailed. The potential of enzymatic hydrolysis to design additives with different bioactivity was shown in the case of plant growth stimulation.


Sign in / Sign up

Export Citation Format

Share Document