scholarly journals Hedera rhombea inhibits the biofilm formation of Candida, thereby increases the susceptibility to antifungal agent, and reduces infection

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258108
Author(s):  
Daseul Kim ◽  
Ki-young Kim
Keyword(s):  
Biofilm Formation ◽  
Map Kinases ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Fungal Growth ◽  
Dimorphic Transition ◽  
Pathway Gene ◽  
Anti Fungal ◽  
Hedera Rhombea

Candida is an opportunistic pathogen and a common cause of fungal infections worldwide. Anti-fungal use against Candida infections has resulted in the appearance of resistant strains. The limited choice of anti-fungal therapy means alternative strategies are needed to control fungal infectious diseases. The aim of this study was to evaluate the inhibition of Candida biofilm formation by Hedera rhombea (Korean name: songak) extract. Biofilm formation was assessed using the crystal violet assay which showed a dose dependent reduction in the presence of extract with the biofilm formation inhibitory concentration of C. albicans (IC50 = 12.5μg/ml), C. tropicalis var. tropicalis (IC50 = 25μg/ml), C. parapsilosis var. parapsilosis (IC50 = 6.25μg/ml), C. glabrata (IC50 = 6.25μg/ml), C. tropicalis (IC50 = 12.5μg/ml), and C. parapsilosis (IC50 = 12.5μg/ml) without directly reducing Candida growth. Treatment with 6.25μg/mL of extract increased the antifungal susceptibility to miconazole from 32% decreasing of fungal growth to 98.8% of that based on the fungal growth assay. Treatment of extract dose-dependently reduced the dimorphic transition of Candida based on the dimorphic transition assay and treatment of 3.125μg/mL of extract completely blocked the adherence of Candida to the HaCaT cells. To know the molecular mechanisms of biofilm formation inhibition by extract, qRT-PCR analysis was done, and the extract was found to dose dependently reduce the expression of hyphal-associated genes (ALS3, ECE1, HWP1, PGA50, and PBR1), extracellular matrix genes (GSC1, ZAP1, ADH5, and CSH1), Ras1-cAMP-PKA pathway genes (CYR1, EFG1, and RAS1), Cph2-Tec1 pathway gene (TEC1) and MAP kinases pathway gene (HST7). In this study, Hedera rhombea extract showed inhibition of fungal biofilm formation, activation of antifungal susceptibility, and reduction of infection. These results suggest that fungal biofilm formation is good screen for developing the antifungal adjuvant and Hedera rhombea extract should be a good candidate against biofilm-related fungal infection.

scholarly journals Adenophora triphylla var. japonica Inhibits Candida Biofilm Formation, Increases Susceptibility to Antifungal Agents and Reduces Infection

2021 ◽  
Vol 22 (22) ◽  
pp. 12523
Author(s):  
Daseul Kim ◽  
Ki-Young Kim
Keyword(s):  
Biofilm Formation ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Fungal Growth ◽  
Pcr Analysis ◽  
Dimorphic Transition ◽  
Pathway Gene ◽  
Good Target ◽  
Gene 4 ◽  
Candida Biofilm

(1) Background: Candida is the most common cause of fungal infections worldwide, but due to the limited option of antifungal therapies, alternative strategies are required. (2) Methods: Adenophora triphylla var. japonica extract was used for the biofilm formation assay using RPMI1640. The combinatorial antifungal assay, the dimorphic transition assay, and the adherence assay were done to see the influence of inhibition of biofilm formation. qRT-PCR analysis were performed to check the gene expression. (3) Results: Adenophora triphylla var. japonica extract inhibited the Candida biofilm formation. Treatment of extract increased the antifungal susceptibility of miconazole from a 37% reduction in fungal growth to 99.05%, and also dose-dependently reduced the dimorphic transition of Candida and the attachment of Candida to HaCaT cells. The extract blocked the expression of hyphal-related genes, extracellular matrix genes, Ras1-cAMP-PKA pathway genes, Cph2-Tec1 pathway gene, and MAP kinase pathway gene. (4) Conclusions: In this study, the treatment of Adenophora triphylla var. japonica extract showed inhibition of fungal biofilm formation, activation of antifungal susceptibility, and reduction of infection. These results suggest that fungal biofilm formation is a good target for the development of antifungal adjuvants, and Adenophora triphylla var. japonica extract should be a good candidate for biofilm-associated fungal infections.

scholarly journals Antifungal susceptibility testing of Aspergillus niger on silicon microwells by intensity-based reflectometric interference spectroscopy

2019 ◽  
Author(s):  
Christopher Heuer ◽  
Heidi Leonard ◽  
Nadav Nitzan ◽  
Ariella Lavy-Alperovitch ◽  
Naama Massad-Ivanir ◽  
...  
Keyword(s):  
Aspergillus Niger ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Fungal Growth ◽  
Antifungal Susceptibility Testing ◽  
Label Free ◽  
Broth Microdilution ◽  
Silicon Phase ◽  
Reflectometric Interference Spectroscopy

AbstractThe increasing number of invasive fungal infections among immunocompromised patients and the emergence of antifungal resistant pathogens has resulted in the need for rapid and reliable antifungal susceptibility testing (AFST). Accelerating antifungal susceptibility testing allows for advanced treatment decisions and the reduction in future instances of antifungal resistance. In this work, we demonstrate the application of a silicon phase grating as sensor for the detection of growth of Aspergillus niger (A. niger) by intensity-based reflectometric interference spectroscopy and its use as an antifungal susceptibility test. The silicon gratings provide a solid-liquid interface to capture micron-sized Aspergillus conidia within microwell arrays. Fungal growth is optically tracked and detected by the reduction in the intensity of reflected light from the silicon grating. The growth of A. niger in the presence of various concentrations of the antifungal agents voriconazole and amphotericin B is investigated by intensity-based reflectometric interference spectroscopy and used for the determination of the minimal inhibitory concentrations (MIC), which are compared to standard broth microdilution testing. This assay allows for expedited detection of fungal growth and provides a label-free alternative to standard antifungal susceptibility testing methods, such as broth microdilution and agar diffusion methods.

scholarly journals Virulence Factors and Azole-Resistant Mechanism of Candida Tropicalis Isolated From Candidemia

2021 ◽  
Author(s):  
Elahe Sasani ◽  
Sadegh Khodavaisy ◽  
Sassan Rezaie ◽  
Mohammadreza Salehi ◽  
Muhammad Getso ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Candida Tropicalis ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Antifungal Susceptibility ◽  
Cell Surface Hydrophobicity ◽  
Surface Hydrophobicity ◽  
Azole Resistance ◽  
Virulence Determinants ◽  
Fluconazole Resistant

Abstract Background Virulence factors intensify the pathogenicity of Candida species in candidemia. Limited knowledge exists regarding the azole-resistant mechanism and virulence factors of Candida tropicalis. Consequently, we aimed to evaluate the virulence factors and the molecular mechanisms of azole resistance among C. tropicalis isolated from bloodstream infection. Materials and methods Forty-five C. tropicalis isolates recovered from candidemia patients were evaluated for virulence factors, including extracellular enzymatic activities, cell surface hydrophobicity (CHS), and biofilm formation. Antifungal susceptibility pattern and expression level of ERG11, UPC2, MDR1, and CDR1 genes of eight azole resistance C. tropicalis isolates were assessed. Results The isolates expressed different frequencies of virulence determinants as follows: coagulase 4 (8.9%), phospholipase 4 (8.9 %), proteinase 31 (68.9 %), CSH 43 (95.6 %), esterase 43 (95.6 %), hemolysin 44 (97.8%), and biofilm formation 45 (100%). All the isolates were susceptible to amphotericin B and showed the highest resistance to voriconazole. The high expression of ERG11 and UPC2 genes in fluconazole-resistant C. tropicalis isolates were observed. Conclusion C. tropicalis isolated from candidemia patients extensively displayed capacities for biofilm formation, hemolysis, esterase activity, and hydrophobicity. In addition, the overexpression of ERG11 and UPC2 genes can be considered as one of the possible mechanisms of azole resistance.

First Case of Invasive Stachybotrys Sinusitis

2020 ◽  
Author(s):  
Margarita Semis ◽  
Sanjeet S Dadwal ◽  
Bernard R Tegtmeier ◽  
Sharon P Wilczynski ◽  
James I Ito ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Sick Building Syndrome ◽  
Pulmonary Hemorrhage ◽  
Fungal Growth ◽  
Hyphal Growth ◽  
Lymphocytic Leukemia ◽  
Sinus Surgery ◽  
First Case ◽  
Clinical Records

Abstract Background The toxigenic mold Stachybotrys has controversially been linked to idiopathic pulmonary hemorrhage and “sick building syndrome.” However, there are no previous clinical records of invasive stachybotryosis. Methods Sinus biopsy specimens from a 23-year-old male with refractory acute lymphocytic leukemia were obtained at 3 different time points during the patient’s hospitalization (139 days) and examined by histopathology and immunohistochemistry (IHC). Antifungal susceptibility testing and fungal speciation using multilocus sequence typing were performed. Results Hemorrhage, fungal germination, and hyphal growth were observed in the first sinus biopsy tissues. Areas with fungal growth tested positive for Stachybotrys by IHC. Fungal isolates were genotyped and identified as Stachybotrys chlorohalonata. The patient was cured from Stachybotrys sinusitis following sinus surgery and antifungal treatment. While a subsequent second sinus biopsy and a bronchoscopy showed no signs of fungal infection, a later, third sinus biopsy tested positive for Aspergillus calidoustus, a rare human pathogen. Conclusions Here, we report the first case of invasive S. chlorohalonata sinusitis that was surgically and medically cured but followed by invasive A. calidoustus sinusitis in the setting of refractory leukemia. Our findings emphasize the risk for unusual fungal infections in severely immunocompromised patients.

scholarly journals Commonly Used Oncology Drugs Decrease Antifungal Effectiveness against Candida and Aspergillus Species

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
Arielle Butts ◽  
Parker Reitler ◽  
Wenbo Ge ◽  
Jarrod R. Fortwendel ◽  
Glen E. Palmer
Keyword(s):  
Treatment Failure ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Fungal Growth ◽  
Content Type ◽  
Medical Interventions ◽  
Azole Antifungals ◽  
Small Collection ◽  
Timely Fashion

ABSTRACT The incidence of invasive fungal infections has risen significantly in recent decades as medical interventions have become increasingly aggressive. These infections are extremely difficult to treat due to the extremely limited repertoire of systemic antifungals, the development of drug resistance, and the extent to which the patient's immune function is compromised. Even when the appropriate antifungal therapies are administered in a timely fashion, treatment failure is common, even in the absence of in vitro microbial resistance. In this study, we screened a small collection of FDA-approved oncolytic agents for compounds that impact the efficacy of the two most widely used classes of systemic antifungals against Candida albicans , Candida glabrata , and Aspergillus fumigatus . We have identified several drugs that enhance fungal growth in the presence of azole antifungals and examine the potential that these drugs directly affect fungal fitness, specifically antifungal susceptibility, and may be contributing to clinical treatment failure.

Adherence and Biofilm Formation in Candida albicans Strains Isolated from Different Infection Sites in Hospitalized Patients

2018 ◽  
Vol 68 (12) ◽  
pp. 2832-2835
Author(s):  
Omar Sadik ◽  
Lia Mara Ditu ◽  
Irina Gheorghe ◽  
Gratiela Gradisteanu Pircalabioru ◽  
Coralia Bleotu ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Respiratory Tract ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Morphological Characteristics ◽  
Stool Culture ◽  
Yeast Cells ◽  
Upper Respiratory Tract ◽  
Adherence Pattern

Adherence of Candida albicans to the cellular and inert substratum contributes to its commensal status, but also plays an essential role in the development of fungal infections, particularly in hospitalized and immunodepressed patients. This study evaluated the adherence capacity and biofilm formation of 109 C. albicans strains isolated from upper respiratory tract secretions, wound secretions, urine culture, blood culture and stool culture taken from patients hospitalized for cardiovascular surgery. The strains were originally identified as C. albicans, based on their morphological characteristics and then confirmed by the Vitek II automatic system. All tested strains adhered to the cellular substratum, the isolates from stool culture, urine and thrush secretion exhibiting the most intensive adhesion capacity, the predominant adherence pattern being the aggregative one. Patient age and gender did not exhibit a significant influence on the adhesion process. The strains with the highest biofilm production capacity were the ones isolated from respiratory tract secretions and urine cultures. Statistically significant correlations could be established among a high number of yeast cells adhered to HeLa cells and i) the aggregative adherence pattern and ii) the moderate to high capacity to form biofilms on the inert substratum. These results could suggest the implication of common fungal structures in the colonization of inert and cellular substrata, while the elucidation of the molecular mechanisms involved in these processes could bring an important benefit to the appropriate management of fungal infections, depending on the isolation source.

scholarly journals Oral Candida colonization in HIV-infected patients in Londrina-PR, Brazil: antifungal susceptibility and virulence factors

2015 ◽  
Vol 9 (12) ◽  
pp. 1350-1359 ◽  
Author(s):  
Suelen Balero De Paula ◽  
Alexandre Tadachi Morey ◽  
Jussevania Pereira Santos ◽  
Pollyanna M. C. Dos Santos ◽  
Danielle G. Gameiro ◽  
...  
Keyword(s):  
Candida Species ◽  
Biofilm Formation ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Cell Surface Hydrophobicity ◽  
Candida Colonization ◽  
Hydrophobic Property ◽  
Predisposing Factor ◽  
Oral Candida

Introduction: Host colonization by Candida species is an important predisposing factor to candidiasis, which seems to be more frequent in human immunodeficiency virus (HIV)-infected patients. Knowledge about the distribution, antifungal susceptibility, and virulence of oral Candida isolates is important for effective management of candidiasis. Methodology: Oral rinses were collected from 242 HIV-infected patients without clinical evidence of candidiasis seen at the AIDS referral center in Londrina, Brazil. Species were identified by standard phenotypic and molecular methods, and characterized in vitro according to antifungal susceptibility, cell surface hydrophobicity, biofilm formation, and enzyme activities. Results: Oral Candida colonization was detected in 50.4% of patients and combined use of antiretroviral therapy and protease inhibitor had a protective effect against colonization. Candida albicans (75.2%) was the most prevalent species. A high proportion of Candida spp. (39.9%) showed decreased susceptibility to fluconazole. Five isolates were resistant to nystatin. Protease and phospholipase activities were detected in 100% and 36.8% of isolates, respectively. Most isolates displayed a hydrophobic property that was associated with biofilm formation ability. Conclusions: A significant number of oral Candida species exhibiting decreased susceptibility to fluconazole were isolated from colonized HIV-infected individuals. Furthermore, all isolates expressed potential virulence attributes in vitro. Given the high incidence and severity of fungal infections in HIV-infected individuals, the results of this study reinforce the importance of antifungal susceptibility testing, which contributes to therapeutic strategies and highlights the need for continuous surveillance of Candida colonization in this population.

scholarly journals Herbal Products and Their Active Constituents Used Alone and in Combination with Antifungal Drugs against Drug-Resistant Candida sp.

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 655
Author(s):  
Anna Herman ◽  
Andrzej Przemysław Herman
Keyword(s):  
Biofilm Formation ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Membrane Transporters ◽  
Drug Resistant ◽  
Herbal Products ◽  
Active Constituents ◽  
Over Expression ◽  
Candida Sp ◽  
Current State

Clinical isolates of Candida yeast are the most common cause of opportunistic fungal infections resistant to certain antifungal drugs. Therefore, it is necessary to detect more effective antifungal agents that would be successful in overcoming such infections. Among them are some herbal products and their active constituents.The purpose of this review is to summarize the current state of knowledge onherbal products and their active constituents havingantifungal activity against drug-resistant Candida sp. used alone and in combination with antifungal drugs.The possible mechanisms of their action on drug-resistant Candida sp. including (1) inhibition of budding yeast transformation into hyphae; (2) inhibition of biofilm formation; (3) inhibition of cell wall or cytoplasmic membrane biosynthesis; (4) ROS production; and (5) over-expression of membrane transporters will be also described.

scholarly journals CD137 Signaling Is Critical in Fungal Clearance during Systemic Candida albicans Infection

2021 ◽  
Vol 7 (5) ◽  
pp. 382
Author(s):  
Vuvi G. Tran ◽  
Na N. Z. Nguyen ◽  
Byungsuk Kwon
Keyword(s):  
Candida Albicans ◽  
Defense Mechanisms ◽  
Tumor Necrosis ◽  
Fungal Infections ◽  
Fungal Growth ◽  
Wild Type ◽  
Agonistic Antibody ◽  
Innate Defense ◽  
Surface Receptor ◽  
Candida Albicans Infection

Invasive fungal infections by Candida albicans frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance during systemic C. albican infection, yet little has been known regarding which surface receptor controls neutrophils’ antifungal activities. CD137, which is encoded by Tnfrsf9, belongs to the tumor necrosis receptor superfamily and has been shown to regulate neutrophils in Gram-positive bacterial infection. Here, we used genetic and immunological tools to probe the involvement of neutrophil CD137 signaling in innate defense mechanisms against systemic C. albicans infection. We first found that Tnfrsf9−/− mice were susceptible to C. albicans infection, whereas injection of anti-CD137 agonistic antibody protected the host from infection, suggesting that CD137 signaling is indispensable for innate immunity against C. albicans infection. Priming of isolated neutrophils with anti-CD137 antibody promoted their phagocytic and fungicidal activities through phospholipase C. In addition, injection of anti-CD137 antibody significantly augmented restriction of fungal growth in Tnfrsf9−/− mice that received wild-type (WT) neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic C. albicans infection by promoting rapid fungal clearance.

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