In-vitro Inhibition of Biofilm Formation in Candida albicans and Candida tropicalis by Heat Stable Compounds in Culture Filtrate of Aspergillus flavus

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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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 Inhibition of Streptococcus mutans Biofilm Formation on Hydroxyapatite by Subinhibitory Concentrations of Anthraquinones

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00999-06 ◽

2007 ◽

Vol 51 (4) ◽

pp. 1541-1544 ◽

Cited By ~ 34

Author(s):

Tom Coenye ◽

Kris Honraet ◽

Petra Rigole ◽

Pol Nadal Jimenez ◽

Hans J. Nelis

Keyword(s):

Reactive Oxygen Species ◽

Streptococcus Mutans ◽

Biofilm Formation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Membrane Perturbation ◽

In Vitro Inhibition ◽

Subinhibitory Concentrations

ABSTRACT We report that certain anthraquinones (AQs) reduce Streptococcus mutans biofilm formation on hydroxyapatite at concentrations below the MIC. Although AQs are known to generate reactive oxygen species, the latter do not underlie the observed effect. Our results suggest that AQs inhibit S. mutans biofilm formation by causing membrane perturbation.

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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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Synergistic Activity of Chloroquine with Fluconazole against Fluconazole-Resistant Isolates of Candida Species

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04417-14 ◽

2014 ◽

Vol 59 (2) ◽

pp. 1365-1369 ◽

Cited By ~ 10

Author(s):

Yali Li ◽

Zhe Wan ◽

Wei Liu ◽

Ruoyu Li

Keyword(s):

Candida Albicans ◽

Synergistic Effect ◽

Candida Tropicalis ◽

Candida Krusei ◽

Synergistic Activity ◽

Broth Microdilution ◽

Content Type ◽

Fluconazole Resistant ◽

Susceptibility Tests

ABSTRACTThein vitroactivity of chloroquine and the interactions of chloroquine combined with fluconazole against 37Candidaisolates were tested using the broth microdilution, disk diffusion, and Etest susceptibility tests. Synergistic effect was detected with 6 of 9 fluconazole-resistantCandida albicansisolates, withCandida kruseiATCC 6258, and with all 12 fluconazole-resistantCandida tropicalisisolates.

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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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Aspectos micológicos e suscetibilidade in vitro de leveduras do gênero Candida em pacientes HIV-positivos provenientes do Estado de Mato Grosso

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822010000600014 ◽

2010 ◽

Vol 43 (6) ◽

pp. 673-677 ◽

Cited By ~ 7

Author(s):

Olivia Cometti Favalessa ◽

Marilena dos Anjos Martins ◽

Rosane Christine Hahn

Keyword(s):

Candida Albicans ◽

Candida Tropicalis ◽

Candida Glabrata ◽

Candida Parapsilosis ◽

Candida Guilliermondii ◽

Candida Krusei ◽

Mato Grosso ◽

Candida Sp

INTRODUÇÃO: A candidíase é uma das infecções fúngicas mais frequentes entre os pacientes infectados pelo vírus da imunodeficiência humana. O presente estudo objetivou a caracterização das leveduras do gênero Candida de distintas amostras clínicas, provenientes de pacientes HIV - positivos, assim como a determinação do perfil de suscetibilidade in vitro a cinco drogas antifúngicas. MÉTODOS: A caracterização dos isolados de Candida sp foi realizada através da metodologia clássica, testes bioquímicos (zimograma e auxanograma) e morfológicos (prova do tubo germinativo e microcultivo em lâmina). Também, foram realizadas a técnica genotípica (PCR) e identificação pelo método comercial API 20C AUX (BioMeriéux). Para a determinação do perfil de suscetibilidade in vitro, foram utilizadas cinco drogas antifúngicas (cetoconazol, fluconazol, itraconazol, voriconazol e anfotericina B), através do método comercialmente disponível - Etest. RESULTADOS: Foram identificados 105 isolados de leveduras do gênero Candida provenientes de 102 pacientes infectados pelo vírus HIV. Destes, foram caracterizadas 82 (78,1%) Candida albicans, 8 (7,6%) Candida parapsilosis, 8 (7,6%) Candida tropicalis, 4 (3,8%) Candida krusei, 2 (1,9%) Candida glabrata e 1 (1%) Candida guilliermondii. CONCLUSÕES: Considerando o perfil geral de sensibilidade, 60% dos isolados foram suscetíveis a todos os antifúngicos testados, porém as espécies C. tropicalis e C. krusei demonstraram uma tendência a valores mais elevados de CIMs para os azóis do que os encontrados paraC. albicans, sugerindo resistência.

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