Alterations in the Level of Ergosterol in Candida albicans' Plasma Membrane Correspond with Changes in Virulence and Result in Triggering Diversed Inflammatory Response.

Opportunistic pathogen Candida albicans possesses multiple virulence factors which enable colonization and infection of host tissues. Candida-related infections frequently occur in immunocompromised patients, which is related to an insufficient inflammatory response. Furthermore, immunosuppression and multidrug resistance of C. albicans clinical isolates make the treatment of candidiasis a challenge for modern medicine. The most common resistance mechanism of C. albicans to antifungals includes point mutations in the ERG11 gene, which encodes target protein for azoles. We investigated whether the mutations or deletion of the ERG11 gene influence the pathogen-host interactions. We prove that both C. albicans erg11∆/∆ and ERG11K143R/K143R exhibit increased cell surface hydrophobicity. Additionally, C. albicans KS058 has an impaired ability of biofilm and hyphae formation. Analysis of the inflammatory response of human dermal fibroblasts and vaginal epithelial cell lines revealed that altered morphology of C. albicans erg11∆/∆ results in a significantly weaker immune response. C. albicans ERG11K143R/K143R triggered stronger production of pro-inflammatory response. Analysis of genes encoding adhesins confirmed differences in the expression pattern of key adhesins for both erg11∆/∆ and ERG11K143R/K143R strains. Obtained data indicate that alterations in Erg11p consequence in resistance to azoles and affect the key virulence factors and inflammatory response of host cells.

Surfactin and Capric Acid Affect the Posaconazole Susceptibility of Candida albicans Strains with Altered Sterols and Sphingolipids Biosynthesis.

Infections caused by Candida spp. pose a continuing challenge for modern medicine, due to widespread resistance to commonly used antifungal agents (e.g., azoles). Thus, there is considerable interest in discovering new, natural compounds that can be used in combination therapy with conventional antibiotics. Here, we investigate whether the natural compounds surfactin and capric acid, in combination with posaconazole, enhance the growth inhibition of C. albicans strains with alterations in sterols and the sphingolipids biosynthesis pathway. We demonstrate that combinations of posaconazole with surfactin or capric acid correspond with the decreased growth of C. albicans strains. Moreover, surfactin and capric acid can independently contribute to the reduced adhesion of C. albicans strains with altered ergosterol biosynthesis to abiotic surfaces (up to 90% reduction in adhesion). A microscopic study of the C. albicans plasma membrane revealed that combinations of those compounds do not correspond with the increased permeabilization of the plasma membrane when compared to cells treated with posaconazole alone. This suggests that the fungistatic effect of posaconazole in combination with surfactin or capric acid is related to the reduction in adhesion of C. albicans.

K143R Amino Acid Substitution in 14-α-Demethylase (Erg11p) Changes Plasma Membrane and Cell Wall Structure of Candida albicans.

The opportunistic pathogen Candida albicans is responsible for life-threating infections in immunocompromised individuals. Azoles and polyenes are two of the most commonly used antifungals and target the ergosterol biosynthesis pathway or ergosterol itself. A limited number of clinically employed antifungals correspond to the development of resistance mechanisms. One resistance mechanism observed in clinical isolates of azole-resistant C. albicans is the introduction of point mutations in the ERG11 gene, which encodes a key enzyme (lanosterol 14-α-demethylase) on the ergosterol biosynthesis pathway. Here, we demonstrate that a point mutation K143R in ERG11 (C. albicans ERG11K143R/K143R) contributes not only to azole resistance, but causes increased gene expression. Overexpression of ERG11 results in increased ergosterol content and a significant reduction in plasma membrane fluidity. Simultaneously, the same point mutation caused cell wall remodeling. This could be facilitated by the unmasking of chitin and ß-glucan on the fungal cell surface, which can lead to recognition of the highly immunogenic ß-glucan, triggering a stronger immunological reaction. For the first time, we report that a frequently occurring azole-resistance strategy makes C. albicans less susceptible to azole treatment while, at the same time, affects its cell wall architecture, potentially leading to exposure of the pathogen to a more effective host immune response.

The Role of Ergosterol and Sphingolipids in the Localization and Activity of Candida albicans' Multidrug Transporter Cdr1p and Plasma Membrane ATPase Pma1p.

Opportunistic pathogen Candida albicans causes systemic infections named candidiasis. Due to the increasing number of multi-drug resistant clinical isolates of Candida sp., currently employed antifungals (e.g., azoles) are insufficient for combating fungal infection. One of the resistance mechanisms toward azoles is increased expression of plasma membrane (PM) transporters (e.g., Cdr1p), and such an effect was observed in C. albicans clinical isolates. At the same time, it has been proven that a decrease in PMs sphingolipids (SLs) content correlates with altered sensitivity to azoles and diminished Cdr1p levels. This indicates an important role for SL in maintaining the properties of PM and gaining resistance to antifungal agents. Here, we prove using a novel spot variation fluorescence correlation spectroscopy (svFCS) technique that CaCdr1p localizes in detergent resistant microdomains (DRMs). Immunoblot analysis confirmed the localization of CaCdr1p in DRMs fraction in both the C. albicans WT and erg11Δ/Δ strains after 14 and 24 h of culture. We also show that the C. albicanserg11Δ/Δ strain is more sensitive to the inhibitor of SLs synthesis; aureobasidin A (AbA). AbA treatment leads to a diminished amount of SLs in C. albicans WT and erg11Δ/Δ PM, while, for C. albicanserg11Δ/Δ, the general levels of mannose-inositol-P-ceramide and inositol-P-ceramide are significantly lower than for the C. albicans WT strain. Simultaneously, the level of ergosterol in the C. albicans WT strain after adding of AbA remains unchanged, compared to the control conditions. Analysis of PM permeabilization revealed that treatment with AbA correlates with the disruption of PM integrity in C. albicanserg11Δ/Δ but not in the C. albicans WT strain. Additionally, in the C. albicans WT strain, we observed lower activity of H+-ATPase, correlated with the delocalization of both CaCdr1p and CaPma1p.

Fructose Induces Fluconazole Resistance in Candida albicans through Activation of Mdr1 and Cdr1 Transporters.

Candida albicans is a pathogenic fungus that is increasingly developing multidrug resistance (MDR), including resistance to azole drugs such as fluconazole (FLC). This is partially a result of the increased synthesis of membrane efflux transporters Cdr1p, Cdr2p, and Mdr1p. Although all these proteins can export FLC, only Cdr1p is expressed constitutively. In this study, the effect of elevated fructose, as a carbon source, on the MDR was evaluated. It was shown that fructose, elevated in the serum of diabetics, promotes FLC resistance. Using C. albicans strains with green fluorescent protein (GFP) tagged MDR transporters, it was determined that the FLC-resistance phenotype occurs as a result of Mdr1p activation and via the increased induction of higher Cdr1p levels. It was observed that fructose-grown C. albicans cells displayed a high efflux activity of both transporters as opposed to glucose-grown cells, which synthesize Cdr1p but not Mdr1p. Additionally, it was concluded that elevated fructose serum levels induce the de novo production of Mdr1p after 60 min. In combination with glucose, however, fructose induces Mdr1p production as soon as after 30 min. It is proposed that fructose may be one of the biochemical factors responsible for Mdr1p production in C. albicans cells.

Lactate Like Fluconazole Reduces Ergosterol Content in the Plasma Membrane and Synergistically Kills Candida albicans.

Candida albicans is an opportunistic pathogen that induces vulvovaginal candidiasis (VVC), among other diseases. In the vaginal environment, the source of carbon for C. albicans can be either lactic acid or its dissociated form, lactate. It has been shown that lactate, similar to the popular antifungal drug fluconazole (FLC), reduces the expression of the ERG11 gene and hence the amount of ergosterol in the plasma membrane. The Cdr1 transporter that effluxes xenobiotics from C. albicans cells, including FLC, is delocalized from the plasma membrane to a vacuole under the influence of lactate. Despite the overexpression of the CDR1 gene and the increased activity of Cdr1p, C. albicans is fourfold more sensitive to FLC in the presence of lactate than when glucose is the source of carbon. We propose synergistic effects of lactate and FLC in that they block Cdr1 activity by delocalization due to changes in the ergosterol content of the plasma membrane.

Antiadhesive Properties of Imidazolium Ionic Liquids Based on (-)-Menthol Against Candida spp.

Infections with Candida spp. are commonly found in long-time denture wearers, and when under immunosuppression can lead to stomatitis. Imidazolium ionic liquids with an alkyl or alkyloxymethyl chain and a natural (1R,2S,5R)-(-)-menthol substituent possess high antifungal and antiadhesive properties towards C. albicans, C. parapsilosis, C. glabrata and C. krusei. We tested three compounds and found they disturbed fungal plasma membranes, with no significant hemolytic properties. In the smallest hemolytic concentrations, all compounds inhibited C. albicans biofilm formation on acrylic, and partially on porcelain and alloy dentures. Biofilm eradication may result from hyphae inhibition (for alkyl derivatives) or cell wall lysis and reduction of adhesins level (for alkyloxymethyl derivative). Thus, we propose the compounds presented herein as potential anti-fungal denture cleaners or denture fixatives, especially due to their low toxicity towards mammalian erythrocytes after short-term exposure.

Lipid composition and cell surface hydrophobicity of Candida albicans influence the efficacy of fluconazole-gentamicin treatment.

Adherence of the fungus, Candida albicans, to biotic (e.g. human tissues) and abiotic (e.g. catheters) surfaces can lead to emergence of opportunistic infections in humans. The process of adhesion and further biofilm development depends, in part, on cell surface hydrophobicity (CSH). In this study, we compared the resistance of C. albicans strains with different CSH to the most commonly prescribed antifungal drug, fluconazole, and the newly described synergistic combination, fluconazole and gentamicin. The hydrophobic strain was more resistant to fluconazole due to, among others, overexpression of the ERG11 gene encoding the fluconazole target protein (CYP51A1, Erg11p), which leads to overproduction of ergosterol in this strain. Additionally, the hydrophobic strain displayed high efflux activity of the multidrug resistance Cdr1 pump due to high expression of the CDR1 gene. On the other hand, the hydrophobic C. albicans strain was more susceptible to fluconazole-gentamicin combination because of its different effect on lipid content in the two strains. The combination resulted in ergosterol depletion with subsequent Cdr1p mislocalization and loss of activity in the hydrophobic strain. We propose that C. albicans strains with different CSH may possess altered lipid metabolism and consequently may differ in their response to treatment.

Antifungal Styryloquinolines as Candida albicans Efflux Pump Inhibitors: Styryloquinolines are ABC Transporter Inhibitors.

Styrylquinolines are heterocyclic compounds that are known for their antifungal and antimicrobial activity. Metal complexation through hydroxyl groups has been claimed to be a plausible mechanism of action for these types of compounds. A series of novel structures with protected hydroxyl groups have been designed and synthesized to verify the literature data. Their antifungal activity against wild-type Candida albicans strain and mutants with silenced efflux pumps activity has been determined. Combinations with fluconazole revealed synergistic interactions that were dependent on the substitution pattern. These results open a new route for designing active antifungal agents on a styrylquinoline scaffold.

Biotransformation of rapeseed meal leading to production of polymers, biosurfactants, and fodder.

After extracting the oil from rapeseed, the remaining meal byproduct is used in animal feed, particularly for cattle, and represents an effective, high-protein substitute for soybean meal. The biotransformation of rapeseed meal using Generally Recognized as Safe (GRAS) bacteria increases its nutritional value and enriches it with a variety of additives including polymers, biosurfactants, and enzymes. Polymers produced in SSF process with rapeseed meal (e.g., levan) have probiotic prosperities and can even serve as alternatives to antibiotics, which are banned from animal feed by law. Due to their moisturizing properties, these polymers are also incorporated into cosmetics. The biosurfactants produced by bacteria and yeast confer their strong antimicrobial effects to preserve the feed. In turn, the many enzymes produced during the biotransformation of rapeseed meal increase its nutritional value by reducing fibers, detrimental substances (e.g., tannins, erucic acid, phytic acid), and mycotoxins. Taken together, rapeseed meal biotransformation results in numerous benefits, for the animal and industry alike.

Coating polypropylene surfaces with protease weakens the adhesion and increases the dispersion of Candida albicans cells.

OBJECTIVES: To investigate the ability of the proteases, subtilisin and α-chymotrypsin (aCT), to inhibit the adhesion of Candida albicans biofilm to a polypropylene surface. RESULTS: The proteases were immobilized on plasma-treated polypropylene by covalently linking them with either glutaraldehyde (GA) or N'-diisopropylcarbodiimide (DIC) and N-hydroxysuccinimide (NHS). The immobilization did not negatively affect the enzyme activity and in the case of subtilisin, the activity was up to 640% higher than that of the free enzyme when using N-acetyl phenylalanine ethyl ester as the substrate. The efficacies against biofilm dispersal for the GA-linked SubC and aCT coatings were 41 and 55% higher than the control (polypropylene coated with only GA), respectively, whereas no effect was observed with enzymes immobilized with DIC and NHS. The higher dispersion efficacy observed for the proteases immobilized with GA could be both steric (proper orientation of the active site) and dynamic (higher protein mobility/flexibility). CONCLUSIONS: Proteases immobilized on a polypropylene surface reduced the adhesion of C. albicans biofilms and therefore may be useful in developing anti-biofilm surfaces based on non-toxic molecules and sustainable strategies.

Reaction of bis[(2-chlorocarbonyl)phenyl] Diselenide with Phenols, Aminophenols, and Other Amines towards Diphenyl Diselenides with Antimicrobial and Antiviral Properties.

A reaction of bis[(2-chlorocarbonyl)phenyl] diselenide with various mono and bisnucleophiles such as aminophenols, phenols, and amines have been studied as a convenient general route to a series of new antimicrobial and antiviral diphenyl diselenides. The compounds, particularly bis[2-(hydroxyphenylcarbamoyl)]phenyl diselenides and reference benzisoselenazol-3(2H)-ones, exhibited high antimicrobial activity against Gram-positive bacterial species (Enterococcus spp., Staphylococcus spp.), and some compounds were also active against Gram-negative E. coli and fungi (Candida spp., A.niger). The majority of compounds demonstrated high activity against human herpes virus type 1 (HHV-1) and moderate activity against encephalomyocarditis virus (EMCV), while they were generally inactive against vesicular stomatitis virus (VSV).

The lipopeptides pseudofactin II and surfactin effectively decrease Candida albicans adhesion and hydrophobicity.

A serious problem for humans is the propensity of Candida albicans to adhere to various surfaces and its ability to form biofilms. Surfactants or biosurfactants can affect the cell surfaces of microorganisms and block their adhesion to different substrates. This study investigated adhesion of C. albicans strains differing in cell surface hydrophobicity (CSH) to polystyrene microplates in order to compare the ability of lipopeptide biosurfactants pseudofactin (PF II) and surfactin (SU) to prevent fungal adhesion to polystyrene. The biosurfactants decreased adhesion of tested strains by 35-90 % when microplates were conditioned before the addition of cells. A 80-90 % reduction of adhesion was observed when cells were incubated together with lipopeptides in microplates. When microplates were pre-coated with biosurfactants, PF II was less active than SU, but when cells were incubated together with biosurfactants, the activity of both compounds was similar, independent of the CSH of strains. When cells were preincubated with lipopeptides and then the compounds were washed out, the adhesion of hydrophobic strains increased two times in comparison to control samples. This suggests irreversible changes in the cell wall after the treatment with biosurfactants. CSH of hydrophobic strains decreased only by 20-60 % after incubation with biosurfactants while adhesion decreased by 80-90 %; the changes in cell adhesion can be thus only partially explained through the modification of CSH. Preincubation of C. albicans with biosurfactants caused extraction of cell wall proteins with molecular mass in the range of 10-40 kDa, which is one possible mechanism of action of the tested lipopeptides.

Isolation and identification of carbon monoxide producing microorganisms from compost.

Carbon monoxide (CO) formation has been observed during composting of various fractions of organic waste. It was reported that this production can be biotic, associated with the activity of microorganisms. However, there are no sources considering the microbial communities producing CO production in compost. This preliminary research aimed to isolate and identify microorganisms potentially responsible for the CO production in compost collected from two areas of the biowaste pile: with low (118 ppm) and high CO concentration (785 ppm). Study proved that all isolates were bacterial strains with the majority of rod-shaped Gram-positive bacteria. Both places can be inhabited by the same bacterial strains, e.g. Bacillus licheniformis and Paenibacillus lactis. The most common were Bacillus (B. licheniformis, B. haynesii, B. paralicheniformis, and B. thermolactis). After incubation of isolates in sealed bioreactors for 4 days, the highest CO levels in the headspace were recorded for B. paralicheniformis (>1000 ppm), B. licheniformis (>800 ppm), and G. thermodenitrificans (∼600 ppm). High CO concentrations were accompanied by low O2 (<6%) and high CO2 levels (>8%). It is recommended to analyze the expression of the gene encoding CODH to confirm or exclude the ability of the identified strains to convert CO2 to CO.

Effects of fermented rapeseed meal on performance, intestinal morphology, the viscosity of intestinal content, phosphorus availability, and egg quality of laying hens.

Fermented rapeseed meal has the potential to partial replace soybean meal in feed mixtures for poultry without a negative impact on the health condition and performance of birds. This is due to the fact that the fermentation process can reduce the amount of antinutritional factors, improve the use of nutrients and impart probiotic properties to rapeseed meal. Therefore, this study was undertaken to investigate the effect of fermented rapeseed meal on the performance, egg quality, intestinal morphometry, the viscosity of intestinal content and total phosphorus availability. A total of 108 Lohmann Brown laying hens at 26 wk of age were used in the 90-day study. All hens were randomly divided into 3 treatment groups, with 12 replicates (cages) each, as follows: control group received no rapeseed meal, the URSM group received 3% unfermented rapeseed meal and the FRSM group received 3% fermented rapeseed meal. In the case of performance, egg traits, sensory evaluation of eggs, the viscosity of intestinal content and the availability of total phosphorus, if the distribution was normal, a 1-way analysis of variance was performed. If the distribution was not normal, the Kruskal-Wallis test was performed. In the case of histomorphometric evaluation of the intestine, if the distribution was normal, the Student t test for independent samples was performed. If not, a Mann-Whitney U test was performed. The performed analyses showed that the supplementation of fermented rapeseed meal had no negative effect on the performance of birds and the quality of eggs. Fermented rapeseed meal was also associated with improved histomorphometric parameters of the small intestine compared to the group receiving unfermented rapeseed meal in the feed. Laying hens from FRSM group were characterized by significantly lower viscosity of intestinal content (P < 0.05) compared to URSM group. Phosphorus in FRSM group was significantly more available to the birds (P < 0.05) compared to URSM group. These results suggest that supplementation with fermented rapeseed meal may be beneficial, especially in times of unstable prices of soybean meal and problems with its availability.

Anticandidal Cu(I) complexes with neocuproine and 1-(4-methoxyphenyl)piperazine based diphenylaminomethylphosphine: Is Cu-diimine moiety a pharmacophore?

The studies on metal complexes as potential antifungals are of growing interest because they may be the answer to increasingly effective defense mechanisms. Herein we present two new copper(I) iodide or thiocyanide complexes with 2,9-dimethyl-1,10-phenanthroline (dmp) and diphenylphosphine derivative of 1-(4-methoxyphenyl)piperazine (4MP): [CuI(dmp)4MP] (1-4MP) and [CuNCS(dmp)4MP] (2-4MP) - their synthesis, as well as structural and spectroscopic characteristics. Interestingly, while 4MP and its oxide derivative (4MOP) show a very low or no activity against all tested Candida albicans strains (MIC50 ≥ 200 µM against CAF2-1 - laboratory control strain, DSY1050 - mutant without transporters Cdr1, Cdr2, Mdr1; isogenic for CAF2-1, and fluconazole resistant clinical isolates), for 1-4MP and 2-4MP MIC50 values were 0.4 µM, independently on the complex and strain tested. Determination of the viability of NHDF-Ad (Normal Adult Human Dermal Fibroblasts) cell line treated with 1-4MP and 2-4MP showed that for both complexes there was only a 20% reduction in the concentration range » to 2 × MIC50 and the 70% at 4 × MIC50. Subsequently, the MLCT based luminescence of the complexes in aqueous media allowed to record the confocal micrographs of 1-4MP in the cells. The results show that it is situated most likely in the vacuoles (C. albicans) or lysosomes (NHDF-Ad).

The alternating 50 Hz magnetic field depending on the hydrophobicity of the strain affects the viability, filamentation and sensitivity to drugs of Candida albicans.

In recent decades, Candida albicans have been the main etiological agent of life-threatening invasive infections, characterized by various mechanisms of resistance to commonly used antifungals. One of the strategies to fight Candida infections may be the use of an electromagnetic field. In this study, we examined the influence of the alternating magnetic field of 50 Hz on the cells of C. albicans. We checked the impact of the alternating magnetic field of 50 Hz on the viability, filamentation and sensitivity to fluconazole and amphotericin B of two, differing in hydrophobicity, strains of C. albicans, CAF2-1 and CAF 4-2. Our results indicate that using the alternating magnetic field of 50 Hz reduces the growth of C. albicans. Interestingly, it presents a stronger effect on the hydrophobic strain CAF4-2 than on the hydrophilic CAF2-1. The applied electromagnetic field also affects the permeabilization of the cell membrane. However, it does not inhibit the transformation from yeast to hyphal forms. AMF is more effective in combination with fluconazole rather than amphotericin B. Our findings confirm the hypothesis that the application of the alternating magnetic field of 50 Hz in antifungal therapy may arise as a new option to support the treatment of Candida infections.

Influence of solid state fermentation with Bacillus subtilis 67 strain on the nutritional value of rapeseed meal and its effects on performance and meat quality of broiler chickens.

The study aimed to evaluate the influence of solid-state fermentation on the nutritional value and enzymatic activity of rapeseed meal and its effects on the performance of broiler chickens and meat quality, including physicochemical properties (proximate analysis, pH, water holding capacity), antioxidant capabilities, dipeptide composition of the meat and sensory traits. Three dietary treatments were evaluated using broiler chickens: a control without incorporation of rapeseed meal; a second treatment with the incorporation of 3% unfermented rapeseed meal; and a third with the incorporation of 3% rapeseed meal fermented with Bacillus subtilis 67. The study showed that fermented compared to unfermented rapeseed meal was characterized by a significantly higher content of dry matter, crude ash, crude fat and metabolic energy (P < 0.05), and a significantly lower content of crude fiber and glucosinolates (P < 0.05). The B. subtilis 67 strain shows cellulolytic and xylulolytic activity. Fermented rapeseed meal has a positive effect on body weight of birds, daily gain, and European Production Efficiency Factor (P < 0.05). Both rapeseed meal treatments significantly reduced the pH of leg muscles and the water-holding capacity of breast muscles (P < 0.05). The fermented meal had a negative impact on some sensory parameters of poultry meat. There was no significant influence of fermented rapeseed meal on the composition of dipeptides in poultry meat and its antioxidant status.

Antiadhesive activity of the biosurfactant pseudofactin II secreted by the Arctic bacterium Pseudomonas fluorescens BD5.

BACKGROUND: Pseudofactin II is a recently identified biosurfactant secreted by Pseudomonas fluorescens BD5, the strain obtained from freshwater from the Arctic Archipelago of Svalbard. Pseudofactin II is a novel compound identified as cyclic lipopeptide with a palmitic acid connected to the terminal amino group of eighth amino acid in peptide moiety. The C-terminal carboxylic group of the last amino acid forms a lactone with the hydroxyl of Thr3. Adhesion is the first stage of biofilm formation and the best moment for the action of antiadhesive and anti-biofilm compounds. Adsorption of biosurfactants to a surface e.g. glass, polystyrene, silicone modifies its hydrophobicity, interfering with the microbial adhesion and desorption processes. In this study the role and applications of pseudofactin II as a antiadhesive compound has been investigated from medicinal and therapeutic perspectives. RESULTS: Pseudofactin II lowered the adhesion to three types of surfaces (glass, polystyrene and silicone) of bacterial strains of five species: Escherichia coli, Enterococcus faecalis, Enterococcus hirae, Staphylococcus epidermidis, Proteus mirabilis and two Candida albicans strains. Pretreatment of a polystyrene surface with 0.5 mg/ml pseudofactin II inhibited bacterial adhesion by 36-90% and that of C. albicans by 92-99%. The same concentration of pseudofactin II dislodged 26-70% of preexisting biofilms grown on previously untreated surfaces. Pseudofactin II also caused a marked inhibition of the initial adhesion of E. faecalis, E. coli, E. hirae and C. albicans strains to silicone urethral catheters. The highest concentration tested (0.5 mg/ml) caused a total growth inhibition of S. epidermidis, partial (18-37%) inhibition of other bacteria and 8-9% inhibition of C. albicans growth. CONCLUSION: Pseudofactin II showed antiadhesive activity against several pathogenic microorganisms which are potential biofilm formers on catheters, implants and internal prostheses. Up to 99% prevention could be achieved by 0.5 mg/ml pseudofactin II. In addition, pseudofactin II dispersed preformed biofilms. Pseudofactin II can be used as a disinfectant or surface coating agent against microbial colonization of different surfaces, e.g. implants or urethral catheters.

The Role of ERG11 Point Mutations in the Resistance of Candida albicans to Fluconazole in the Presence of Lactate.

Candidiasis refers to both superficial and deep-tissue fungal infections often caused by Candida albicans. The treatment of choice for these infections is the use of azoles, such as fluconazole (FLC). However, the increased use of antifungal agents has led to the emergence of azole-resistant isolates of C. albicans. Thus, the development of alternative drugs that are more efficient and with a better toxicological profile is necessary. This study aimed to determine the susceptibility profile of C. albicans CAF2-1 strain to FLC in the presence of glucose or lactate. The research was also focused on single nucleotide polymorphism (SNP) and the determination of the effect of the identified point mutations on the amino acid sequence of the Erg11 protein. The results show the growth of C. albicans CAF2-1 in the presence of FLC was significantly lower in the presence of lactate than in glucose. As a result, among recorded 45 amino acid mutations, the following mutations may be associated with the reduced susceptibility of C. albicans to FLC: G10D, G10V, I11M, I11R, Y13N, F31V, L35F, A249D, Q250H, E266G, R267G, N273K, D275C, D275G, D275R. Moreover, a twice higher number of hot-spot mutations was found in the presence of glucose as a sole carbon source compared to cells grown on lactate.