scholarly journals The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance

2020 ◽  
Vol 21 (7) ◽  
pp. 2654 ◽  
Author(s):  
Kuang-Ting Cheng ◽  
Chih-Lung Wu ◽  
Bak-Sau Yip ◽  
Ya-Han Chih ◽  
Kuang-Li Peng ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Antimicrobial Peptide ◽  
Oral Candidiasis ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Salivary Protein ◽  
Histatin 5 ◽  
C Terminus

In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, Candida albicans, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with Candida albicans or its degradation by Candida-secreted proteases that contribute to the fungi’s resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living Candida albicans cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications.

scholarly journals Antifungal Activity of Oleylphosphocholine on In Vitro and In Vivo Candida albicans Biofilms

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Michelle Holtappels ◽  
Erwin Swinnen ◽  
Lies De Groef ◽  
Jurgen Wuyts ◽  
Lieve Moons ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Biofilm Formation ◽  
Ex Vivo ◽  
Oral Candidiasis ◽  
Sprague Dawley ◽  
Content Type ◽  
Polyurethane Catheters

ABSTRACT In this study, we investigated the potential antifungal activity of the alkylphospholipid oleylphosphocholine (OlPC), a structural analogue of miltefosine, on in vitro and in vivo Candida albicans biofilm formation. The effect of OlPC on in vitro and in vivo C. albicans biofilms inside triple-lumen polyurethane catheters was studied. In vivo biofilms were developed subcutaneously after catheter implantation on the lower back of Sprague-Dawley rats. Animals were treated orally with OlPC (20 mg/kg of body weight/day) for 7 days. The effect of OlPC on biofilms that developed on the mucosal surface was studied in an ex vivo model of oral candidiasis. The role of OlPC in C. albicans morphogenesis was investigated by using hypha-inducing media, namely, Lee, Spider, and RPMI 1640 media. OlPC displayed activity against both planktonic cells and in vitro C. albicans biofilms. To completely abolish preformed, 24-h-old biofilms, higher concentrations (8, 10, and 13 mg/liter) were needed. Moreover, OlPC was able to reduce C. albicans biofilms formed by caspofungin-resistant clinical isolates and acted synergistically when combined with caspofungin. The daily oral administration of OlPC significantly reduced in vivo C. albicans biofilms that developed subcutaneously. In addition, OlPC decreased biofilm formation on mucosal surfaces. Interestingly, the application of subinhibitory concentrations of OlPC already inhibited the yeast-to-hypha transition, a crucial virulence factor of C. albicans. We document, for the first time, the effects of OlPC on C. albicans cells and suggest the potential use of OlPC for the treatment of C. albicans biofilm-associated infections.

scholarly journals A Peptide Found in Human Serum, Derived from the C-Terminus of Albumin, Shows Antifungal Activity In Vitro and In Vivo

2020 ◽  
Vol 8 (10) ◽  
pp. 1627
Author(s):  
Tecla Ciociola ◽  
Pier Paolo Zanello ◽  
Tiziana D’Adda ◽  
Serena Galati ◽  
Stefania Conti ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Human Serum ◽  
Fungicidal Activity ◽  
Galleria Mellonella ◽  
Serum Proteins ◽  
Morphological Alterations ◽  
C Terminus ◽  
Different Sources

The growing problem of antimicrobial resistance highlights the need for alternative strategies to combat infections. From this perspective, there is a considerable interest in natural molecules obtained from different sources, which are shown to be active against microorganisms, either alone or in association with conventional drugs. In this paper, peptides with the same sequence of fragments, found in human serum, derived from physiological proteins, were evaluated for their antifungal activity. A 13-residue peptide, representing the 597–609 fragment within the albumin C-terminus, was proved to exert a fungicidal activity in vitro against pathogenic yeasts and a therapeutic effect in vivo in the experimental model of candidal infection in Galleria mellonella. Studies by confocal microscopy and transmission and scanning electron microscopy demonstrated that the peptide penetrates and accumulates in Candida albicans cells, causing gross morphological alterations in cellular structure. These findings add albumin to the group of proteins, which already includes hemoglobin and antibodies, that could give rise to cryptic antimicrobial fragments, and could suggest their role in anti-infective homeostasis. The study of bioactive fragments from serum proteins could open interesting perspectives for the development of new antimicrobial molecules derived by natural sources.

scholarly journals Orodispersible Film Loaded with Enterococcus faecium CRL183 Presents Anti-Candida albicans Biofilm Activity In Vitro

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 998
Author(s):  
Virgínia Barreto Lordello ◽  
Andréia Bagliotti Meneguin ◽  
Sarah Raquel de Annunzio ◽  
Maria Pía Taranto ◽  
Marlus Chorilli ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Enterococcus Faecium ◽  
Potato Starch ◽  
Oral Candidiasis ◽  
Candida Spp ◽  
Sem Images ◽  
Control Film ◽  
In Vitro Antifungal Activity

Background: Probiotic bacteria have been emerging as a trustworthy choice for the prevention and treatment of Candida spp. infections. This study aimed to develop and characterize an orodispersible film (ODF) for delivering the potentially probiotic Enterococcus faecium CRL 183 into the oral cavity, evaluating its in vitro antifungal activity against Candida albicans. Methods and Results: The ODF was composed by carboxymethylcellulose, gelatin, and potato starch, and its physical, chemical, and mechanical properties were studied. The probiotic resistance and viability during processing and storage were evaluated as well as its in vitro antifungal activity against C. albicans. The ODFs were thin, resistant, and flexible, with neutral pH and microbiologically safe. The probiotic resisted the ODF obtaining process, demonstrating high viability (>9 log10 CFU·g−1), up to 90 days of storage at room temperature. The Probiotic Film promoted 68.9% of reduction in fungal early biofilm and 91.2% in its mature biofilm compared to the group stimulated with the control film. Those results were confirmed through SEM images. Conclusion: The probiotic ODF developed is a promising strategy to prevent oral candidiasis, since it permits the local probiotic delivery, which in turn was able to reduce C. albicans biofilm formation.

Spilanthol as a promising antifungal alkylamide for the treatment of vulvovaginal candidiasis

2021 ◽  
Author(s):  
Rodrigo L Fabri ◽  
Jhamine C O Freitas ◽  
Ari S O Lemos ◽  
Lara M Campos ◽  
Irley O M Diniz ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Cell Membrane ◽  
Multidrug Resistant ◽  
Fungal Strain ◽  
Vulvovaginal Candidiasis ◽  
Biofilm Matrix

Abstract Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remains to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis model. Our in vitro analyses in C. albicans planktonic cultures detected a significant inhibitory effect of spilanthol(AcO), which affects both yeast cell membrane and cell wall integrity, interfering with the fungus growth. C. albicans biofilm proliferation and adhesion, as well as, carbohydrates and DNA in biofilm matrix were reduced after spilanthol(AcO) treatment. Moreover, infected rats treated with spilanthol(AcO) showed consistent reduction of both fungal burden and inflammatory processes compared to the untreated animals. Altogether, our findings demonstrated that spilanthol(AcO) is an bioactive compound against planktonic and biofilm forms of a multidrug resistant C. albicans strain. Furthermore, spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans. Lay Abstract This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.

The ultrastructure of Candida albicans infections

1981 ◽  
Vol 27 (11) ◽  
pp. 1156-1164 ◽  
Author(s):  
Thomas J. Marrie ◽  
J. William Costerton
Keyword(s):  
Candida Albicans ◽  
Oral Candidiasis ◽  
Ruthenium Red ◽  
Host Cells ◽  
Yeast Cells ◽  
Positive Matrix ◽  
Urine Sediment ◽  
Bacteria Adhesion

Scrapings of Candida albicans plaques from the tongue and buccal mucosa of patients with oral candidiasis were examined electron microscopy. In addition, urine sediment from patients with infection of their catheterized urinary tracts was similar examined. Three types of C. albicans – oral epithelial cell interactions were noted: a loose adherence apparently mediated by ruthenium red positive matrix, a "tight" adherence where no space could be seen between the host and yeast cell, and invasions host cells by yeast hyphal elements. Adhesion of Candida blastospores to hyphal elements and adhesion of bacteria to Candida cells was also frequently observed.Urine sediments from patients with mixed bacteria–yeast infections demonstrated adhesion of the bacteria to the yeast cells. This phenomenon was also demonstrated in in vitro experiments and fibrous ruthenium red material invariably occupied the zo*** of adhesion.Phagocytosis of yeast by polymorphonuclear leukocytes was found in urinary, but not in oral, candidiasis. Our in vivo and vitro observations indicate that a ruthenium red positive matrix covers the surfaces involved in the yeast to yeast, yeast to ho and yeast to bacteria adhesion.

scholarly journals Antimicrobial Photodynamic Therapy in Combination with Nystatin in the Treatment of Experimental Oral Candidiasis Induced by Candida albicans Resistant to Fluconazole

2019 ◽  
Vol 12 (3) ◽  
pp. 140 ◽  
Author(s):  
Karem Janeth Rimachi Hidalgo ◽  
Juliana Cabrini Carmello ◽  
Cláudia Carolina Jordão ◽  
Paula Aboud Barbugli ◽  
Carlos Alberto de Sousa Costa ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Photodynamic Therapy ◽  
Combined Therapy ◽  
Oral Candidiasis ◽  
Confocal Scanning Laser Microscopy ◽  
Antimicrobial Photodynamic Therapy ◽  
Promising Alternative ◽  
Confocal Scanning ◽  
Confocal Scanning Laser

Background: It has been demonstrated that azole-resistant strains of Candida albicans have a greater resistance to antimicrobial photodynamic therapy (aPDT) when compared to their more susceptible counterparts. For this reason, the present study evaluated the efficacy of aPDT, together with nystatin (NYS), in the treatment of oral candidiasis in vivo. Methods: Mice were infected with fluconazole-resistant C. albicans (ATCC 96901). To perform the combined therapy, aPDT, mediated by Photodithazine (PDZ) and LED light, was used together with NYS. The efficacy of the treatments was evaluated by microbiological, macroscopic, histopathological and Confocal Scanning Laser Microscopy analyses of the lesions. The expression of p21 and p53, proteins associated with cell death, from the tongues of mice, was also performed. Results: The combined therapy reduced the fungal viability by around 2.6 log10 and decreased the oral lesions and the inflammatory reaction. Additionally, it stimulated the production of p53 and p21. Conclusions: The combined therapy is a promising alternative treatment for oral candidiasis induced by C. albicans resistant to fluconazole.

scholarly journals Effects of salivary protein flow and indigenous microorganisms on initial colonization of Candida albicans in an in vivo model

2012 ◽  
Vol 12 (1) ◽  
Author(s):  
Norihiko Kanaguchi ◽  
Naoki Narisawa ◽  
Tatsuro Ito ◽  
Yosuke Kinoshita ◽  
Yasuka Kusumoto ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Salivary Protein ◽  
In Vivo Model ◽  
Indigenous Microorganisms

scholarly journals Efficient transmission and persistence of low‐frequency SIVmac251 variants in CD8-depleted rhesus macaques with different neuropathology

2012 ◽  
Vol 93 (5) ◽  
pp. 925-938 ◽  
Author(s):  
Samantha L. Strickland ◽  
Rebecca R. Gray ◽  
Susanna L. Lamers ◽  
Tricia H. Burdo ◽  
Ellen Huenink ◽  
...  
Keyword(s):  
Rhesus Macaques ◽  
Disease Model ◽  
Low Frequency ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Post Mortem ◽  
Viral Heterogeneity ◽  
Signature Pattern ◽  
Efficient Transmission

Infection of CD8-depleted rhesus macaques with the genetically heterogeneous simian immunodeficiency virus (SIV)mac251 viral swarm provides a rapid-disease model for simian acquired immune deficiency syndrome and SIV-encephalitis (SIVE). The objective was to evaluate how the diversity of the swarm influences the initial seeding of the infection that may potentially affect disease progression. Plasma, lymphoid and non-lymphoid (brain and lung) tissues were collected from two infected macaques euthanized at 21 days post-infection (p.i.), as well as longitudinal specimens and post-mortem tissues from four macaques followed throughout the infection. About 1300 gp120 viral sequences were obtained from the infecting SIVmac251 swarm and the macaques longitudinal and post-mortem samples. Phylogenetic and amino acid signature pattern analyses were carried out to assess frequency, transmission dynamics and persistence of specific viral clusters. Although no significant reduction in viral heterogeneity was found early in infection (21 days p.i.), transmission and replication of SIV variants was not entirely random. In particular, two distinct motifs under-represented (<4 %) in the infecting swarm were found at high frequencies (up to 14 %) in all six macaques as early as 21 days p.i. Moreover, a macrophage tropic variant not detected in the viral swarm (<0.3 %) was present at high frequency (29–100 %) in sequences derived from the brain of two macaques with meningitis or severe SIVE. This study demonstrates the highly efficient transmission and persistence in vivo of multiple low frequency SIVmac251 founder variants, characterized by specific gp120 motifs that may be linked to pathogenesis in the rapid-disease model of neuroAIDS.

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