Virulence Factors Of Candida Species Research Articles

Antifungal activity of the ethanolic extract and flavonoid avicularin from Myrcia tomentosa (Aubl.) DC. on virulence factors of Candida species

In this work, the mechanism of the action of the ethanolic extract and avicularin isolated from Myrcia tomentosa was evaluated against Candida albicans and Candida parapsilosis. The effects of ethanolic extract and avicularin regarding adhesion in epithelial cells and on yeast kinetic growth were tested. A neutral red uptake (NRU) assay was used to test cytotoxicity against the 3T3-A31 cells of Balb/c. The morphology and ultrastructural analysis were examined by scanning and transmission electron microscopy. The results showed good activity for the ethanolic extract and the flavonoid avicularin, which inhibited the yeasts in concentrations of 32 and 16 µg/mL, respectively. The plant samples promoted inhibition of the adhesion in epithelial cells and showed a reduction in the number of the yeasts in kinetic growth. Avicularin and ethanolic extract from M. tomentosa showed low in vitro toxicity for the 3T3-A31 cells. The scanning and transmission electron microscopy showed changes in morphology and cell arrangement of Candida species in the presence of avicularin. Considering the results, avicularin obtained from M. tomentosa demonstrates potential for the future treatment of candidiasis.

Growing importance of urogenital candidiasis in individuals with diabetes: A narrative review.

Both diabetes and fungal infections contribute significantly to the global disease burden, with increasing trends seen in most developed and developing countries during recent decades. This is reflected in urogenital infections caused by Candida species that are becoming ever more pervasive in diabetic patients, particularly those that present with unsatisfactory glycemic control. In addition, a relatively new group of anti-hyperglycemic drugs, known as sodium glucose cotransporter 2 inhibitors, has been linked with an increased risk for colonization of the urogenital region with Candida spp., which can subsequently lead to an infectious process. In this review paper, we have highlighted notable virulence factors of Candida species (with an emphasis on Candida albicans) and shown how the interplay of many pathophysiological factors can give rise to vulvovaginal candidiasis, potentially complicated with recurrences and dire pregnancy outcomes. We have also addressed an increased risk of candiduria and urinary tract infections caused by species of Candida in females and males with diabetes, further highlighting possible complications such as emphysematous cystitis as well as the risk for the development of balanitis and balanoposthitis in (primarily uncircumcised) males. With a steadily increasing global burden of diabetes, urogenital mycotic infections will undoubtedly become more prevalent in the future; hence, there is a need for an evidence-based approach from both clinical and public health perspectives.

(MeOPhSe)2, a synthetic organic selenium compound, inhibits virulence factors of Candida krusei: Adherence to cervical epithelial cells and biofilm formation

BackgroundSystemic candidiasis is produced by Candida albicans or non-albicans Candida species, opportunistic fungi that produce both superficial and invasive infections. Despite the availability of a wide range of antifungal agents for the treatment of candidiasis, failure of therapy is observed frequently, which opens new avenues in the field of alternative therapeutic strategies. MethodsThe effects of p,p′-methoxyl-diphenyl diselenide [(MeOPhSe)2], a synthetic organic selenium (organochalcogen) compound, were investigated on virulence factors of C. krusei and compared with its antifungal effects on the virulence factors related to adhesion to cervical epithelial cell surfaces with C. albicans. Results(MeOPhSe)2, a compound non-toxic in epithelial (HeLa) and fibroblastic (Vero) cells, inhibited the growth in a dose-dependent manner and changed the kinetics parameters of C. krusei and, most importantly, extending the duration of lag phase of growth, inhibiting biofilm formation, and changing the structure of biofilm. Also, (MeOPhSe)2 reduced C. albicans and C. krusei adherence to cervical epithelial cells, an important factor for the early stage of the Candida-host interaction. The reduction was 37.24 ± 2.7 % in C. krusei (p = 0.00153) and 32.84 ± 3.2 % in C. albicans (p = 0.0072) at 20 µM (MeOPhSe)2, and the effect is in a concentration-dependent manner. Surprisingly, the antifungal potential on adhesion was similar between both species, indicating the potential of (MeOPhSe)2 as a promising antifungal drug against different Candida infections. ConclusionOverall, we demonstrated the potential of (MeOPhSe)2 as an effective antifungal drug against the virulence factors of Candida species.

Green synthesis of silver nanoparticles using mixed leaves aqueous extract of wild olive and pistachio: characterization, antioxidant, antimicrobial and effect on virulence factors of Candida.

In this study, a successfully rapid, simple approach was applied for biosynthesis of silver nanoparticles AgNPs using for the first time the mixed leaves extract of Olea europaea subsp. europaea var. sylvestris and Pistacia lentiscus from natural association aimed to enhance their antimicrobial potential. The plant extract acts both as reducing and capping agents. When the aqueous extract was added to AgNO3 solution, the color was changed from pale to yellow to brown indicating the reduction of Ag ions and synthesis of silver nanoparticles (AgNPs) without any solvent or hazardous reagents. The green synthesized AgNPs were characterized by UV-Vis spectrophotometer, FTIR spectrum and the X-ray crystallography. The AgNPs showed superior antioxidant activity measured by DPPH, Ferric Antioxidant Reducing Power (FRAP) as well as the total antioxidant activity methods. Moreover, the analysis of phytochemical constituents including flavonoids, tannins, alkaloids and total polyphenols contents mentioned the most richness of the silver nanoparticles compared to plant extract. The new synthesized AgNPs demonstrated the bactericidal and fungicidal effects against all the tested bacterial and fungal strains and found to limit the spore germination of filamentous fungi. AgNPs also gave an anti-biofilm activity and synergistic effect with the conventional antibiotic's drugs. Here we firstly describe the silver nanoparticles effect on virulence factors of Candida species by reduction of enzymes like proteinase and phospholipase, inhibition of morphogenesis of Candida albicans cells. This natural product, acquiring these properties, should be promoted to be used in pharmaceutical and medical industries in future.

Genotyping, drug resistance and virulence factors of Candida species isolated from patients using long-term inhaled steroids.

In this study, it was aimed to determine the isolation frequency and species distribution of Candida species isolated from asthmatic patients using long-term inhaled steroids. It was also aimed to determine the drug resistance patterns and the frequency of erg11, HWP1, ALS1, INT1, SAP1 PLB1 genes in isolates. Genotyping of Candida strains isolated from patients and healthy control group was performed by PCR-RFLP method. Drug resistance was investigated phenotypically, and the presence of erg11 resistance genes and HWP1, ALS1, INT1, SAP1 PLB1 virulence genes were investigated by PCR method. C albicans was the most isolated species in steroid-using patients and healthy control groups (patients: 44.2%; control group: 30.8%). C tropicalis and C glabrata were found to have the highest rates of non-albicans Candida in patients with 17.4% and 13.77%, respectively. Azole resistance was found to be significantly higher in isolates isolated from patients compared to the control group. Similarly, the presence of erg11 resistance gene was highest in C albicans (17.65%), C glabrata (12.5%) and C tropicalis (8.3%) strains in the control group, while C parapsilosis was highest in patients. (57.1%) and C glabrata (54.2%) strains. Compared to the control group, the virulence of Candida strains isolated from the patients was found to be higher. Presence of HWP1, ALS1, INT1, SAP1 and PLB1 genes in patients were determined as 72.1%, 63.9%, 68.9%, 57.38% and 54.5%, respectively. These rates were 29.4%, 35.3%, 25.5%, 17.7% and 23.5% in the healthy control group, respectively. In asthma patients using long-term inhaled steroids, both Isolation rates of Candida species, drug resistance rates, presence of virulence genes were found to be significantly higher in patients than in the control group. We think that this may be due to the suppression of cellular immunity by long-term steroid use.

A novel study on the inhibitory effect of marine macroalgal extracts on hyphal growth and biofilm formation of candidemia isolates

Biofilm formation and hyphal growth are considered to be the most serious virulence factors of Candida species in blood causing candidemia infections, which are difficult to treat due to the spread of resistant Candida isolates to most antifungal drugs. Therefore, in this study, we investigated the effect of different types and concentrations of selected macroalgal extracts from Cladostephus spongiosus (Phaeophyta), Laurencia papillosa (Rhodophyta), and Codium arabicum (Chlorophyta) in inhibiting those virulence factors of the isolated Candida. Acetone extract of C. spongiosus (AECS) showed a stronger anticandidal activity against the selected strains than ethanol extract. Candida krusei was the highest biofilm producer among the selected isolates. AECS showed an inhibition of C. krusei biofilm formation as well as a reduction in the viability of preformed biofilms. Also, AECS reduced various sugars in the candidal exo-polysaccaride layer (EPS). Scanning electron microscopy (SEM) and light microscopic images revealed an absence of hyphae and an alteration in the morphology of biofilm cells when treated with AECS. Moreover, AECS downregulated the expression of hyphal specific genes, hyphal wall protein 1 (HWP1), Agglutinin-like protein 1 (ALS1) and fourth secreted aspartyl proteinase (SAP4), which confirmed the inhibitory effect of AECS on hyphal growth and biofilm formation. Gas chromatography-mass spectrophotometer (GC-MS) analysis of AECS showed three major compounds, which were non-existent in the ethanol extract, and might be responsible for the anticandidal activity; these revealed compounds were 4-hydroxy-4-methyl-2-pentanone, n-hexadecenoic acid, and phenol, 2-methoxy-4-(2-propenyl). These active compounds of AECS may be promising for future pharmaceutical applications in the treatment of candidemia.

Effect of Cinnamomum verum leaf essential oil on virulence factors of Candida species and determination of the in-vivo toxicity with Galleria mellonella model.

BACKGROUND Essential oils (EO) extracted from Cinnamomum verum has been used as an antimicrobial agents for centuries. The effects of C. verum leaf oil against virulence of microorganisms is not well studied yet.OBJECTIVES This study evaluates the effect of C. verum leaf oil against three virulence factors of Candida albicans, C. tropicalis and C. dubliniensis and its in-vivo toxicity.METHODS Chemical composition of EO was determined using gas chromatography-mass spectrometry (GC-MS). Minimum inhibitory concentration (MIC) was determined using clinical and laboratory standards institute (CLSI) M27-A3 broth microdilution. Effect of EO on initial adhesion was quantified using XTT assay after allowing Candida cells to adhere to the polystyrene surface for 2 h. Biofilm formation of Candida in the presence of EO was quantified using XTT viability assay. Efficacy on reduction of germ tube formation was evaluated using standard protocol. Visualisation of biofilm formation and progression under the EO treatment were done using scanning electron microscope (SEM) and Time lapses microscope respectively. In-vivo toxicity of EO was determined using Galleria mellonella larvae. Chlorhexidine digluconate: positive control.RESULTS Eugenol was the main compound of EO. MIC was 1.0 mg/mL. 50% reduction in initial adhesion was achieved by C. albicans, C. tropicalis and C. dubliniensis with 1.0, > 2.0 and 0.34 mg/mL respectively. 0.5 and 1.0 mg/mL significantly inhibit the germ tube formation. MBIC50 for forming biofilms were ≤ 0.35 mg/mL. 1.0 mg/mL prevent biofilm progression of Candida. SEM images exhibited cell wall damages, cellular shrinkages and decreased hyphal formation. No lethal effect was noted with in-vivo experiment model at any concentration tested.CONCLUSION C. verum leaf oil acts against virulence factors of Candida and does not show any toxicity.

Virulence Factors of candida Species Isolated From Pulmonary Tuberculosis with Diabetes Mellitus

Virulence Factors of candida Species Isolated From Pulmonary Tuberculosis with Diabetes Mellitus

Virulence factors of Candida species from the oral mucosa and prostheses of elderly people from a riverside community in the Amazon state, Brazil

Abstract Introduction Candida albicans is the yeast most commonly affecting the oral cavity, sometimes causing infection. However, several factors may be associated with the onset of candidiasis, which may be related not only to the hygiene and health of individuals, but also to the pathogenicity of these microorganisms. Objective To evaluate the virulence factors of Candida yeasts isolated from the oral mucosa of elderly people living in the “Comunidade Lago do Limão”, municipality of Iranduba, Amazonas state, Brazil. Material and method Testes were performed to assess the production of urease, proteinase, phospholipase and hemolysin. Statistical analysis used the Fisher's exact test and the Chi-squared test. Result Prevalence of non-albicans species was observed. As for virulence factors, all isolates were negative ureases, and there was prevalence of very strong proteinase production, whereas most isolates did not produce this enzyme in the phospholipase test. All yeasts analyzed presented hemolysin production, with grade IV hemolysis as the most prevalent. There was no statistically significant difference between the virulence of isolates from the oral cavity and the prostheses of the elderly analyzed. Conclusion Several virulence factors may present with high intensity in the presence of oral microbiota changes. In addition, non-albicans species present number of virulence factors similar to that of C. albicans, with high pathogenicity. This study allows a better analysis of candidiasis prevention strategies aiming to promote improvement in the health and quality of life for the elderly.

Green synthesized silver nanoparticles demonstrating enhanced in vitro and in vivo antibiofilm activity against Candida spp.

Candida species are opportunistic fungal pathogens, which are known for their biofilm associated infections on implanted medical devices in clinical settings. Broad spectrum usage of azole groups and other antifungal agents leads to the occurrence of drug resistance among Candida species. Most of the antifungal agents have failed to treat the biofilm mediated Candida infections. In the present study, silver nanoparticles (AgNPs) were synthesized using Dodonaea viscosa and Hyptis suoveolens methanolic leaf extracts and characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction analysis, Fourier transform infrared spectroscopy and Scanning electron microscopy, Dynamic light scattering, and Zeta potential analysis. The main goal of this study was to assess the AgNPs for their antibiofilm efficacy against Candida spp. through microscopic analysis and in vitro virulence assays. The results revealed that AgNPs strongly inhibited more than 80% biofilm formed by Candida spp. Furthermore, the AgNPs also reduced the yeast-to-hyphal transition, exopolysaccharide biosynthesis, secreted aspartyl proteinase production which are the major virulence factors of Candida species. This study reveals that biosynthesized AgNPs can be considered for the treatment of biofilm related Candida infections.

Genotypes and virulence factors of Candida species isolated from oralcavities of patients with type 2 diabetes mellitus.

This study compared the genotypes and virulence factors of Candida species isolated from oral cavities of healthy individuals and patients with diabetes mellitus (DM). A total of 142 healthy individuals and 73 diabetic patients participated in this study. Study populations were classified into 4 groups as follows: Group I - Healthy, without caries; Group II - Healthy, with caries; Group III - DM, with caries; Group IV - DM, without caries. Diabetic patients' blood glucose and hemoglobin A1c concentrations were determined. Identification of Candida species was performed with conventional methods. Biofilm production, proteinase, phospholipase, and esterase were analyzed. The genetic diversity of Candida species was established using rep-PCR. The most isolated species was Candida albicans. There were statistical differences in terms of isolated Candida frequency between healthy subjects and diabetic patients. There was no statistical difference between the virulence factors of groups. Twelve genotypes were determined. While there were statistical differences in aerobe biofilm production, proteinase, and phospholipase activity between genotypes, there were no statistical differences in anaerobe biofilm production and esterase activity between genotypes. Diabetes has no effect on the activities of virulence factors of Candida species. Different genotypes of Candida albicans exhibited different virulence activities.

Evaluation of Virulence Factors of Candida Species Isolated from Superficial versus Systemic Candidiasis

Background: Various virulence factors are contributing to the colonization and pathogenicity of Candida during both superficial and systemic infections Objectives: The current study was conducted to investigate production of extracellular hydrolytic enzymes, hemolysis and biofilm formation among Candida species isolated from superficial versus systemic candidiasis and to compare the production of these virulence factors among albicans and non-albicans Candida species, in addition to comparing hemolysis and hydrolytic enzymes production under aerobic and anaerobic conditions. Methodology: A total of 51 Candida strains isolated from vulvovaginal candidiasis and 44 strains isolated from systemic candidiasis were included in the study. Germ tube test and Hi Crom Candida Differential Agar medium were used for species identification of the isolates. The Candida isolates were tested for expression of hemolytic activity, phospholipase, proteinase and esterase production under aerobic and anaerobic conditions, in addition to their ability of biofilm formation. Results: In both groups, 55 isolates were identified as Candida albicans (C. albicans), while 44 isolates were identified as non-albicans species. Hemolytic activity and biofilm formation were significantly higher among the systemic Candida isolates than superficial isolates, while expression of proteinase activity was significantly higher among superficial isolates. Expression of phospholipase and esterase was significantly higher among C. albicans isolates than non-albicans isolates. Expression of proteinase and esterase activities was significantly better under aerobic conditions than under anaerobic conditions. Conclusions: Hemolytic activity and bioflm formation were more evident among the systemic isolates while proteinase production appears to be more evident among the vaginal isolates. Phospholipase production is almost an exclusive characteristic feature of C. albicans, while C. albicans is the leading species in terms of esterase production. Aerobic conditions favor expression of proteinase and esterase activities.

English

The yeast Candida is a normal flora of the skin and the mucous membrane and it then becomes pathogen in immunocompromised people. Various virulence factors are contributing to establishment of the infection in the host. Adherence of the pathogen to host tissues, yeast-hyphal transition and extracellular hydrolytic enzymes secretion are important virulence factors of Candida species. These hydrolytic enzymes play important roles in pathogenicity of Candida infection. The present study was conducted with an aim to determine in vitro phospholipase, proteinase, haemolysin, esterase activities and biofilm formation in oral Candida isolates. A total of 38 Candida species were isolated from oral cavity of patients with symptoms of oral candidiasis. The specimens were identified by standard mycological techniques up to species level and were investigated for production of hydrolytic enzymes and biofilm formation. Phospholipase activity was in 52.6% of isolates, 86.8% produced proteinase and haemolysin activity was seen in 63.1%, esterase activity was demonstrated in 50% of isolates, 78.9% of Candida isolates showed biofilm formation. Candida albicans showed more extracellular hydrolytic enzyme activity, whereas, Candida tropicalis showed more biofilm formation. Both the C. albicans and Non-albicans Candida (NAC) species are capable of producing extracellular hydrolytic enzymes and biofilm formation. Key words: Candida species, virulence factors, extracellular hydrolytic enzymes, biofilm formation.

The Effect of Zuccagnia punctata, an Argentine Medicinal Plant, on Virulence Factors from Candida Species

Zuccagnia punctata Cav. has been used as a traditional medicine in Argentina for the treatment of bacterial and fungal infections. In this study, we evaluated the ability of Z. punctata extract (ZpE) and compounds isolated from it to inhibit the growth and virulence factors of Candida species. ZpE showed inhibitory activity against planktonic cells of all assayed Candida species with MIC values of 400 microg/mL and with MFC values between 400 and 1,200 microg/mL. The principal identified compounds by HPLC-MS/MS and UV-VIS were chalcones (2',4'-dihydroxy-3'-methoxychalcone, 2',4'- dihydroxychalcone), flavones (galangin, 3,7-dihydroxyflavone and chrysin) and flavanones (naringenin, 7-hydroxyflavanone and pinocembrine). These compounds were more effective as inhibitors than the extracts upon biofilm formation as well as on preformed Candida biofilm and yeast germ tube formation. Furthermore, ZpE and chalcones are able to inhibit exoenzymes, which are responsible for the invasion mechanisms of the pathogens. All these effects could moderate colonization, thereby suppressing the pathogen invasive potential. Our results indicate that ZpE and chalcones could be used in antifungal therapy.

Candida Species Adhesion to Oral Epithelium: Factors Involved and Experimental Methodology Used

Due to the increasing prevalence and emergence of Non-Candida albicans Candida (NCAC) species, especially in immunosupressed patients, it is becoming urgent to deepen the current knowledge about virulence factors of these species. Adhesion of cells to epithelium is considered one of the major virulence factors of Candida species. However, relatively little is known concerning the adhesion mechanisms of NCAC species to epithelium, as well as about the factors affecting the adhesion process. This review focuses both the mechanisms that regulate the adhesion interactions and the factors involved and the description of the experimental methodology that has been used to perform the adhesion assays.

Putative virulence factors ofCandidaspecies colonizing respiratory tracts of patients

Putative virulence factors of<i>Candida</i>species colonizing respiratory tracts of patients

Secreted aspartic proteases as virulence factors of Candida species.

Candida infections have emerged as a significant medical problem during the last few decades. Among the different virulence traits of C. albicans, secreted proteolytic activity has been intensively investigated. Pathogenesis of the various forms of candidiasis was shown to be associated with the differential and temporal regulation of the expression of genes coding for secreted aspartic proteases (Sap). These enzymes act as cytolysins in macrophages after phagocytosis of Candida, are present in tissue penetration and are also involved in adherence to epithelial cells. Since the introduction of new antiretroviral therapeutics such as HIV protease inhibitors, oropharyngeal candidiasis is less often observed in AIDS patients. Different HIV aspartic protease inhibitors were able to inhibit the C. albicans Saps involved in adherence. The lower rates of oropharyngeal candidiasis observed in individuals receiving antiretroviral combination therapy could reflect not only an improvement in the immune system but also direct inhibition of Candida Saps by HIV protease inhibitors. Therefore, the development of specific aspartic protease inhibitors might be of interest for the inhibition of candidiasis.