In vitro biofilm formation of Candida albicans and non-albicans Candida species under dynamic and anaerobic conditions

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

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Eap1p, an Adhesin That Mediates Candida albicans Biofilm Formation In Vitro and In Vivo

Eukaryotic Cell ◽

10.1128/ec.00049-07 ◽

2007 ◽

Vol 6 (6) ◽

pp. 931-939 ◽

Cited By ~ 96

Author(s):

Fang Li ◽

Michael J. Svarovsky ◽

Amy J. Karlsson ◽

Joel P. Wagner ◽

Karen Marchillo ◽

...

Keyword(s):

Candida Albicans ◽

Cell Adhesion ◽

Biofilm Formation ◽

Fungal Infections ◽

Gene Dosage ◽

Venous Catheter ◽

Flow Chamber ◽

Dependent Manner

ABSTRACT Candida albicans is the leading cause of systemic fungal infections in immunocompromised humans. The ability to form biofilms on surfaces in the host or on implanted medical devices enhances C. albicans virulence, leading to antimicrobial resistance and providing a reservoir for infection. Biofilm formation is a complex multicellular process consisting of cell adhesion, cell growth, morphogenic switching between yeast form and filamentous states, and quorum sensing. Here we describe the role of the C. albicans EAP1 gene, which encodes a glycosylphosphatidylinositol-anchored, glucan-cross-linked cell wall protein, in adhesion and biofilm formation in vitro and in vivo. Deleting EAP1 reduced cell adhesion to polystyrene and epithelial cells in a gene dosage-dependent manner. Furthermore, EAP1 expression was required for C. albicans biofilm formation in an in vitro parallel plate flow chamber model and in an in vivo rat central venous catheter model. EAP1 expression was upregulated in biofilm-associated cells in vitro and in vivo. Our results illustrate an association between Eap1p-mediated adhesion and biofilm formation in vitro and in vivo.

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Symbiotic NCR Peptide Fragments Affect the Viability, Morphology and Biofilm Formation of Candida Species

International Journal of Molecular Sciences ◽

10.3390/ijms22073666 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3666

Author(s):

Bettina Szerencsés ◽

Attila Gácser ◽

Gabriella Endre ◽

Ildikó Domonkos ◽

Hilda Tiricz ◽

...

Keyword(s):

Candida Species ◽

Biofilm Formation ◽

Therapeutic Potential ◽

Fungal Infections ◽

Combined Treatment ◽

Antimicrobial Activities ◽

Dilution Method ◽

Model Legume ◽

Anticandidal Activity

The increasing rate of fungal infections causes global problems not only in human healthcare but agriculture as well. To combat fungal pathogens limited numbers of antifungal agents are available therefore alternative drugs are needed. Antimicrobial peptides are potent candidates because of their broad activity spectrum and their diverse mode of actions. The model legume Medicago truncatula produces >700 nodule specific cysteine-rich (NCR) peptides in symbiosis and many of them have in vitro antimicrobial activities without considerable toxicity on human cells. In this work we demonstrate the anticandidal activity of the NCR335 and NCR169 peptide derivatives against five Candida species by using the micro-dilution method, measuring inhibition of biofilm formation with the XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay, and assessing the morphological change of dimorphic Candida species by microscopy. We show that both the N- and C-terminal regions of NCR335 possess anticandidal activity as well as the C-terminal sequence of NCR169. The active peptides inhibit biofilm formation and the yeast-hypha transformation. Combined treatment of C. auris with peptides and fluconazole revealed synergistic interactions and reduced 2-8-fold the minimal inhibitory concentrations. Our results demonstrate that shortening NCR peptides can even enhance and broaden their anticandidal activity and therapeutic potential.

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Anaerobic Conditions Induce Expression of Polysaccharide Intercellular Adhesin in Staphylococcus aureus and Staphylococcus epidermidis

Infection and Immunity ◽

10.1128/iai.69.6.4079-4085.2001 ◽

2001 ◽

Vol 69 (6) ◽

pp. 4079-4085 ◽

Cited By ~ 222

Author(s):

Sarah E. Cramton ◽

Martina Ulrich ◽

Friedrich Götz ◽

Gerd Döring

Keyword(s):

Staphylococcus Aureus ◽

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Extracellular Polysaccharide ◽

Growth Conditions ◽

Anaerobic Conditions ◽

Anaerobic Environment ◽

Specific Mrna

ABSTRACT Products of the intercellular adhesion (ica) operon in Staphylococcus aureus and Staphylococcus epidermidis synthesize a linear β-1,6-linked glucosaminylglycan. This extracellular polysaccharide mediates bacterial cell-cell adhesion and is required for biofilm formation, which is thought to increase the virulence of both pathogens in association with prosthetic biomedical implants. The environmental signal(s) that triggers ica gene product and polysaccharide expression is unknown. Here we demonstrate that anaerobic in vitro growth conditions lead to increased polysaccharide expression in both S. aureus and S. epidermidis, although the regulation is less stringent inS. epidermidis. Anaerobiosis also dramatically stimulates ica-specific mRNA expression inica- and polysaccharide-positive strains of both S. aureus and S. epidermidis.These data suggest a mechanism whereby ica gene expression and polysaccharide production may act as a virulence factor in an anaerobic environment in vivo.

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Disparate Candida albicans Biofilm Formation in Clinical Lipid Emulsions Due to Capric Acid-Mediated Inhibition

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01394-19 ◽

2019 ◽

Vol 63 (11) ◽

Author(s):

Hubertine M. E. Willems ◽

Jeremy S. Stultz ◽

Molly E. Coltrane ◽

Jabez P. Fortwendel ◽

Brian M. Peters

Keyword(s):

Candida Albicans ◽

Biofilm Formation ◽

Bloodstream Infections ◽

Capric Acid ◽

Lipid Emulsions ◽

Biofilm Growth ◽

Content Type ◽

Biofilm Model ◽

Hypha Formation

ABSTRACT Receipt of parenteral nutrition (PN) remains an independent risk factor for developing catheter-related bloodstream infections (CR-BSI) caused by fungi, including by the polymorphic fungus Candida albicans, which is notoriously adept at forming drug-resistant biofilm structures. Among a variety of macronutrients, PN solutions contain lipid emulsions to supply daily essential fats and are often delivered via central venous catheters (CVCs). Therefore, using an in vitro biofilm model system, we sought to determine whether various clinical lipid emulsions differentially impacted biofilm growth in C. albicans. We observed that the lipid emulsions Intralipid and Omegaven both stimulated C. albicans biofilm formation during growth in minimal medium or a macronutrient PN solution. Conversely, Smoflipid inhibited C. albicans biofilm formation by approximately 50%. Follow-up studies revealed that while Smoflipid did not impair C. albicans growth, it did significantly inhibit hypha formation and hyphal elongation. Moreover, growth inhibition could be recapitulated in Intralipid when supplemented with capric acid—a fatty acid present in Smoflipid but absent in Intralipid. Capric acid was also found to dose dependently inhibit C. albicans biofilm formation in PN solutions. This is the first study to directly compare different clinical lipid emulsions for their capacity to affect C. albicans biofilm growth. Results derived from this study necessitate further research regarding different lipid emulsions and rates of fungus-associated CR-BSIs.

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Targeting Fibronectin To Disrupt In Vivo Candida albicans Biofilms

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03094-15 ◽

2016 ◽

Vol 60 (5) ◽

pp. 3152-3155 ◽

Cited By ~ 7

Author(s):

Jeniel E. Nett ◽

Jonathan Cabezas-Olcoz ◽

Karen Marchillo ◽

Deane F. Mosher ◽

David R. Andes

Keyword(s):

Candida Albicans ◽

Biofilm Formation ◽

Drug Targets ◽

Venous Catheter ◽

Surface Adhesion ◽

Inhibitory Protein ◽

Content Type ◽

Novel Target

ABSTRACTNew drug targets are of great interest for the treatment of fungal biofilms, which are routinely resistant to antifungal therapies. We theorized that the interaction ofCandida albicanswith matricellular host proteins would provide a novel target. Here, we show that an inhibitory protein (FUD) targetingCandida-fibronectin interactions disrupts biofilm formationin vitroandin vivoin a rat venous catheter model. The peptide appears to act by blocking the surface adhesion ofCandida, halting biofilm formation.

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In Vitro Characterization of a Biaryl Amide Anti-virulence Compound Targeting Candida albicans Filamentation and Biofilm Formation

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2018.00227 ◽

2018 ◽

Vol 8 ◽

Cited By ~ 7

Author(s):

Jesus A. Romo ◽

Christopher G. Pierce ◽

Marisol Esqueda ◽

Chiung-Yu Hung ◽

Stephen. P. Saville ◽

...

Keyword(s):

Candida Albicans ◽

Biofilm Formation ◽

In Vitro Characterization

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Antibody response to the 45 kDa Candida albicans antigen in an animal model and potential role of the antigen in adherence

Journal of Medical Microbiology ◽

10.1099/jmm.0.2008/001479-0 ◽

2008 ◽

Vol 57 (12) ◽

pp. 1466-1472 ◽

Cited By ~ 14

Author(s):

Helena Bujdáková ◽

Ema Paulovičová ◽

Silvia Borecká-Melkusová ◽

Juraj Gašperík ◽

Soňa Kucharíková ◽

...

Keyword(s):

Animal Model ◽

Candida Albicans ◽

Biofilm Formation ◽

Laser Scanning ◽

Vaccine Development ◽

Laser Scanning Microscopy ◽

Model Systems ◽

Confocal Laser

The Candida antigen CR3-RP (complement receptor 3-related protein) is supposed to be a ‘mimicry’ protein because of its ability to bind antibody directed against the α subunit of the mammalian CR3 (CD11b/CD18). This study aimed to (i) investigate the specific humoral isotypic response to immunization with CR3-RP in vivo in a rabbit animal model, and (ii) determine the role of CR3-RP in the adherence of Candida albicans in vitro using the model systems of buccal epithelial cells (BECs) and biofilm formation. The synthetic C. albicans peptide DINGGGATLPQ corresponding to 11 amino-acids of the CR3-RP sequence DINGGGATLPQALXQITGVIT, determined by N-terminal sequencing, was used for immunization of rabbits to obtain polyclonal anti-CR3-PR serum and for subsequent characterization of the humoral isotypic response of rabbits. A significant increase of IgG, IgA and IgM anti-CR3-RP specific antibodies was observed after the third (P<0.01) and the fourth (P<0.001) immunization doses. The elevation of IgA levels suggested peptide immunomodulation of the IgA1 subclass, presumably in coincidence with Candida epithelial adherence. Blocking CR3-RP with polyclonal anti-CR3-RP serum reduced the ability of Candida to adhere to BECs, in comparison with the control, by up to 35 % (P<0.001), and reduced biofilm formation by 28 % (P<0.001), including changes in biofilm thickness and integrity detected by confocal laser scanning microscopy. These properties of CR3-RP suggest that it has potential for future vaccine development.

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Biofilm Formation by Candida Species on Silicone Surfaces and Latex Pacifier Nipples: An in vitro Study

Journal of Clinical Pediatric Dentistry ◽

10.17796/jcpd.33.3.7572960tn46837k4 ◽

2009 ◽

Vol 33 (3) ◽

pp. 235-240 ◽

Cited By ~ 15

Author(s):

Luiz Cezar da Silveira ◽

Senda Charone ◽

Lucianne Cople Maia ◽

Rosangela Maria de Araújo Soares ◽

Maristela Barbosa Portela

Keyword(s):

Candida Species ◽

Biofilm Formation ◽

In Vitro Study ◽

Reduction Reaction ◽

Fungal Colonization ◽

Candida Spp ◽

Biofilm Growth ◽

Species Analysis ◽

Biofilm Development

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

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Oral Administration of the Broad-Spectrum Antibiofilm Compound Toremifene Inhibits Candida albicans and Staphylococcus aureus Biofilm FormationIn Vivo

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03869-14 ◽

2014 ◽

Vol 58 (12) ◽

pp. 7606-7610 ◽

Cited By ~ 16

Author(s):

Kaat De Cremer ◽

Nicolas Delattin ◽

Katrijn De Brucker ◽

Annelies Peeters ◽

Soña Kucharíková ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Candida Albicans ◽

Broad Spectrum ◽

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Candida Krusei ◽

Content Type ◽

And Staphylococcus Aureus

ABSTRACTWe here report on thein vitroactivity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, includingCandida albicans,Candida glabrata,Candida dubliniensis,Candida krusei,Pseudomonas aeruginosa,Staphylococcus aureus, andStaphylococcus epidermidis. We validated thein vivoefficacy of orally administered toremifene againstC. albicans and S. aureusbiofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound.

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