scholarly journals Candida albicans Biofilm Inhibition by Two Vaccinium macrocarpon (Cranberry) Urinary Metabolites: 5-(3′,4′-DihydroxyPhenyl)-γ-Valerolactone and 4-Hydroxybenzoic Acid

2021 ◽  
Vol 9 (7) ◽  
pp. 1492
Author(s):  
Emerenziana Ottaviano ◽  
Giovanna Baron ◽  
Laura Fumagalli ◽  
Jessica Leite ◽  
Elisa Adele Colombo ◽  
...  

Candida spp. are pathobionts, as they can switch from commensals to pathogens, responsible for a variety of pathological processes. Adhesion to surfaces, morphological switch and biofilm-forming ability are the recognized virulence factors promoting yeast virulence. Sessile lifestyle also favors fungal persistence and antifungal tolerance. In this study, we investigated, in vitro, the efficacy of two urinary cranberry metabolites, 5-(3′,4′-dihydroxy phenyl)-γ-valerolactone (VAL) and 4-hydroxybenzoic acid (4-HBA), in inhibiting C. albicans adhesion and biofilm formation. Both the reference strain SC5314 and clinical isolates were used. We evaluated biomass reduction, by confocal microscopy and crystal violet assay, and the possible mechanisms mediating their inhibitory effects. Both VAL and 4-HBA were able to interfere with the yeast adhesion, by modulating the expression of key genes, HWP1 and ALS3. A significant dose-dependent reduction in biofilm biomass and metabolic activity was also recorded. Our data showed that the two cranberry metabolites VAL and 4-HBA could pave the way for drug development, for targeting the very early phases of biofilm formation and for preventing genitourinary Candida infections.

Author(s):  
Lisandra Juvêncio da Silva ◽  
Fátima Daiana Dias Barroso ◽  
Lucas Sousa Vieira ◽  
Daniel Roberto Carlos Mota ◽  
Bruna Kelly da Silva Firmino ◽  
...  

The genus Candida spp. has been highlighted as one of the main etiological agents causing fungal infections, with Candida albicans being the most prominent, responsible for most cases of candidemia. Due to its capacity for invasion and tissue adhesion, it is associated with the formation of biofilms, mainly in the environment and hospital devices, decreasing the effectiveness of available treatments. The repositioning of drugs, which is characterized by the use of drugs already on the market for other purposes, together with molecular-docking methods can be used aiming at the faster development of new antifungals to combat micro-organisms. This study aimed to evaluate the antifungal effect of diazepam on mature C. albicans biofilms in vitro and its action on biofilm in formation, as well as its mechanism of action and interaction with structures related to the adhesion of C. albicans, ALS3 and SAP5. To determine the MIC, the broth microdilution test was used according to protocol M27-A3 (CLSI, 2008). In vitro biofilm formation tests were performed using 96-well plates, followed by molecular-docking protocols to analyse the binding agent interaction with ALS3 and SAP5 targets. The results indicate that diazepam has antimicrobial activity against planktonic cells of Candida spp. and C. albicans biofilms, interacting with important virulence factors related to biofilm formation (ALS3 and SAP5). In addition, treatment with diazepam triggered a series of events in C. albicans cells, such as loss of membrane integrity, mitochondrial depolarization and increased production of EROs, causing DNA damage and consequent cell apoptosis.


2014 ◽  
Vol 21 (9) ◽  
pp. 1206-1214 ◽  
Author(s):  
Lin Yan ◽  
Lei Zhang ◽  
Hongyan Ma ◽  
David Chiu ◽  
James D. Bryers

ABSTRACTNosocomial infections are the fourth leading cause of morbidity and mortality in the United States, resulting in 2 million infections and ∼100,000 deaths each year. More than 60% of these infections are associated with some type of biomedical device.Staphylococcus epidermidisis a commensal bacterium of the human skin and is the most common nosocomial pathogen infecting implanted medical devices, especially those in the cardiovasculature.S. epidermidisantibiotic resistance and biofilm formation on inert surfaces make these infections hard to treat. Accumulation-associated protein (Aap), a cell wall-anchored protein ofS. epidermidis, is considered one of the most important proteins involved in the formation ofS. epidermidisbiofilm. A small recombinant protein vaccine comprising a single B-repeat domain (Brpt1.0) ofS. epidermidisRP62A Aap was developed, and the vaccine's efficacy was evaluatedin vitrowith a biofilm inhibition assay andin vivoin a murine model of biomaterial-associated infection. A high IgG antibody response againstS. epidermidisRP62A was detected in the sera of the mice after two subcutaneous immunizations with Brpt1.0 coadministered with Freund's adjuvant. Sera from Brpt1.0-immunized mice inhibitedin vitroS. epidermidisRP62A biofilm formation in a dose-dependent pattern. After receiving two immunizations, each mouse was surgically implanted with a porous scaffold disk containing 5 × 106CFU ofS. epidermidisRP62A. Weight changes, inflammatory markers, and histological assay results after challenge withS. epidermidisindicated that the mice immunized with Brpt1.0 exhibited significantly higher resistance toS. epidermidisRP62A implant infection than the control mice. Day 8 postchallenge, there was a significantly lower number of bacteria in scaffold sections and surrounding tissues and a lower residual inflammatory response to the infected scaffold disks for the Brpt1.0-immunized mice than for of the ovalbumin (Ova)-immunized mice.


Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 327 ◽  
Author(s):  
Mariana Espinosa-Valdés ◽  
Sara Borbolla-Alvarez ◽  
Ana Delgado-Espinosa ◽  
Juan Sánchez-Tejeda ◽  
Anabelle Cerón-Nava ◽  
...  

Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N-acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa. All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins.


Toxins ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 532
Author(s):  
Amanda Pissinatti Canelli ◽  
Taís Fernanda dos Santos Rodrigues ◽  
Vivian Fernandes Furletti de Goes ◽  
Guilherme Ferreira Caetano ◽  
Maurício Ventura Mazzi

The growing number of oral infections caused by the Candida species are becoming harder to treat as the commonly used antibiotics become less effective. This drawback has led to the search for alternative strategies of treatment, which include the use of antifungal molecules derived from natural products. Herein, crotoxin (CTX), the main toxin of Crotalus durissus terrificus venom, was challenged against Candida tropicalis (CBS94) and Candida dubliniensis (CBS7987) strains by in vitro antimicrobial susceptibility tests. Minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and inhibition of biofilm formation were evaluated after CTX treatment. In addition, CTX-induced cytotoxicity in HaCaT cells was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) colorimetric assay. Native CTX showed a higher antimicrobial activity (MIC = 47 μg/mL) when compared to CTX-containing mouthwash (MIC = 750 μg/mL) and nystatin (MIC = 375 μg/mL). Candida spp biofilm formation was more sensitive to both CTX and CTX-containing mouthwash (IC100 = 12 μg/mL) when compared to nystatin (IC100 > 47 μg/mL). Moreover, significant membrane permeabilization at concentrations of 1.5 and 47 µg/mL was observed. Native CTX was less cytotoxic to HaCaT cells than CTX-containing mouthwash or nystatin between 24 and 48 h. These preliminary findings highlight the potential use of CTX in the treatment of oral candidiasis caused by resistant strains.


2016 ◽  
Vol 62 (9) ◽  
pp. 735-743 ◽  
Author(s):  
Barcin Ozturk ◽  
Necati Gunay ◽  
Bulent M. Ertugrul ◽  
Serhan Sakarya

Bacteria may hide in a hydrated polysaccharide matrix known as a biofilm. The structure of the bacterial biofilm renders phagocytosis difficult and increases antibiotic resistance. We hypothesized that repeated doses of antibiotics have an effect on bacteria within the biofilm and that it could inhibit or eradicate biofilm formation. Two clinical biofilm-positive coagulase-negative staphylococcus isolates were evaluated. The effects of antibiotics on preformed and nascent biofilm and on bacterial eradication within the biofilm were determined using different doses of vancomycin, daptomycin, and tigecycline for different durations in an in vitro biofilm model. Vancomycin neither penetrated the biofilm nor had any microbicidal effect on bacteria within the biofilm. Daptomycin had a microbicidal effect on bacteria within the biofilm but had no effect on biofilm inhibition and eradication (independent from dose and treatment time). Tigecycline inhibited and eradicated biofilm formation and had a microbicidal effect on bacteria within the biofilm. In conclusion, (i) biofilm formation appeared to be a major barrier to vancomycin activity, (ii) daptomycin had an antimicrobial effect on the bacteria within the biofilm but not on the biofilm burden, and (iii) tigecycline had effects both on bacteria within the biofilm and on biofilm burden. Thus, both tigecycline and daptomycin might be promising candidates for the treatment of biofilm infections.


2014 ◽  
Vol 5 (1) ◽  
pp. 55-70 ◽  
Author(s):  
D. Dhanasekaran ◽  
K. Vinothini ◽  
S. Latha ◽  
N. Thajuddin ◽  
A. Panneerselvam

2001 ◽  
Vol 168 (2) ◽  
pp. 333-338 ◽  
Author(s):  
JM Burczynski ◽  
JM Voigt ◽  
PA Longhurst ◽  
HD Colby ◽  

Previous studies demonstrated high levels of lipid peroxidation (LP) in the guinea pig adrenal cortex. The present studies were done to determine if adrenal LP activity was influenced by ACTH, the major hormonal regulator of the gland. Guinea pigs were treated with ACTH for 1, 3 or 7 days. In addition, some guinea pigs received ACTH for 7 days and were killed 3 or 7 days later. After treatment, adrenal microsomal fractions were prepared and incubated in vitro with 1 mM ferrous sulfate to initiate LP. ACTH treatment caused a progressive decrease in adrenal LP; activity was almost totally inhibited within 3 days. The inhibitory effects of ACTH on LP were dose-dependent. Following cessation of ACTH treatment, adrenal LP gradually returned toward control levels. Microsomal concentrations of linoleic acid, a major substrate for adrenal LP, were increased by ACTH administration and then also returned to control levels after cessation of treatment. There were no significant changes in adrenal alpha-tocopherol or beta-carotene concentrations resulting from ACTH treatment. The results indicate that ACTH has a role in the regulation of adrenal LP. The actions of ACTH cannot be attributed to an increase in adrenal content of the antioxidants, alpha-tocopherol and beta-carotene, or to a decrease in LP substrate. The actions of ACTH to inhibit LP may contribute to an increase in adrenal hormone production by protecting steroidogenic enzymes from peroxidative degradation.


2009 ◽  
Vol 33 (3) ◽  
pp. 235-240 ◽  
Author(s):  
Luiz Cezar da Silveira ◽  
Senda Charone ◽  
Lucianne Cople Maia ◽  
Rosangela Maria de Araújo Soares ◽  
Maristela Barbosa Portela

The present study assessed the growth and development of biofilm formation by isolates of C. albicans, C. glabrata and C. parapsilosis on silicone and latex pacifier nipples. The silicone and latex surfaces were evaluated by scanning electronic microscopy (SEM). The plastic component of the nipple also seems to be an important factor regarding the biofilm formation by Candida spp. The biofilm growth was measured using the MTT reduction reaction. C. albicans was found to have a slightly greater capacity of forming biofilm compared to the other Candida species. Analysis of the pattern of biofilm development by C. albicans,C. glabrata and C. parapsilosis on latex and silicon pacifier shields showed an increased biofilm formation regarding the latter substrate. Silicone was shown to be more resistant to fungal colonization, particularly in the case of C. parapsilosis, despite the lack of any statistically significant differences (P > 0.05). In addition, silicone has a smoother surface compared to latex, whose surface was found to be rugose and irregular


2010 ◽  
Vol 5 (6) ◽  
pp. 821-826
Author(s):  
Monika Staniszewska ◽  
Beata Rozbicka ◽  
Aleksandra Rajnisz ◽  
Ewa Bocian ◽  
Ewa Wasińska ◽  
...  

AbstractThe incidence of candidiasis among immunocompromised patients and emergence of antimycotics resistant strains has increased significantly. The aims of this study were: to examine the in vitro activity of antimycotics and biocides against Candida clinical isolates; to detect cross-resistance of fungi to these preparations and to estimate whether disinfectants applied in hospital areas are active against clinical Candida isolates. In vitro susceptibility of 102 Candida isolates to eight antimycotics was examined by Etest and ATB Fungus. Sensitivity of these strains to four disinfectants and an antiseptic agent was tested according to EN 1275:2005. Amphotericin B, caspofungin and 5-fluorocytosine were the most effective antimycotics against all Candida isolates. Resistance to itraconazole and fluconazole was observed among C. krusei and C. glabrata. The MICs (Minimal Inhibitory Concentrations) for ketoconazole, voriconazole and posaconazole against Candida albicans ranged: 0.003 - >32 μg/ml and one strain was resistant to three agents tested. All analysed Candida strains were sensitive to biocides containing either chlorine, aldehyde, alcohol mixtures, glucoprotamin or chlorhexidine gluconate with isopropanol. Sensitivity to these agents was observed at concentrations lower than those concentrations recommended by manufacturers to achieve proper biocidal activity to those preparations. Our data suggest that these disinfectants can be effectively applied in clinical wards to prevent nosocomial Candida infections.


Author(s):  
Mashaeal Saud Alshilawi, Howard Foster

The formation of S. epidermidis and P. aeruginosa biofilms were successfully inhibited in the presence of sub-inhibitory concentrations of S. aromaticum (clove) and L. angustifolia (lavender) essential oils. These substances achieved good in-vitro test results. On the other hand, pure and organic types of N. sativa (black seed) essential oil did not exhibit any inhibitory effects on the biofilm formed by the tested bacteria. Although the tested essential oils may share a similar mechanism of action, ANOVA analysis showed strong statistical differences between all essential oils at their sub-MIC levels, and also identified two different trends, biofilm inhibitors, represented by S. aromaticum (clove) and L. angustifolia (lavender) oils, and biofilm stimulators, represented by both types of N. sativa (black seed) oils. A more thorough perspective on the research question could be achieved by considering the various elements that have essentially contributed to the processes and the findings within this study.


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