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The Synergistic Effect of Zinc Ferrite Nanoparticles Uniformly Deposited on Silver Nanowires for the Biofilm Inhibition of Candida albicans.

ABSTRACT: Near-monodisperse zinc ferrite nanoparticles (ZnFe₂O₄ NPs) are synthesized by a co-precipitation method and deposited on the surface of silver nanowires (AgNWs), employing a stepwise solution method. The resulting hybrid nanostructures (ZnFe₂O₄@AgNWs) show a thin and uniform layer of ZnFe₂O₄ NPs at an optimum weight ratio of 1:6 between the two component nanostructures. The hybrid nanostructures retain the high crystal quality and phase purity of their constituents. It is demonstrated that the ZnFe₂O₄@AgNWs hybrid nanostructures are effective at inhibiting the biofilm formation of Candida albicans cells. The biofilm inhibition activity of the hybrid nanostructures is estimated to be more than 50% at a low concentration of 100 µg/mL from both crystal violet assay and XTT assay, which are more than 8-fold higher than those of pure AgNWs and ZnFe₂O₄ NPs. This greatly enhanced biofilm inhibition activity is attributed to the ZnFe₂O₄ NPs-carrying membrane penetration by AgNWs and the subsequent interaction between Candida cells and ZnFe₂O₄ NPs. These results indicate that the ZnFe₂O₄@AgNWs hybrid nanostructures have great potential as a new type of novel antibiofilm agent.

SUBMITTER: Thakur D

PROVIDER: S-EPMC6835689 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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The Synergistic Effect of Zinc Ferrite Nanoparticles Uniformly Deposited on Silver Nanowires for the Biofilm Inhibition of Candida albicans.

Thakur Deepika D Govindaraju Saravanan S Yun KyuSik K Noh Jin-Seo JS

Nanomaterials (Basel, Switzerland) 20191010 10

Near-monodisperse zinc ferrite nanoparticles (ZnFe2O4 NPs) are synthesized by a co-precipitation method and deposited on the surface of silver nanowires (AgNWs), employing a stepwise solution method. The resulting hybrid nanostructures (ZnFe2O4@AgNWs) show a thin and uniform layer of ZnFe2O4 NPs at an optimum weight ratio of 1:6 between the two component nanostructures. The hybrid nanostructures retain the high crystal quality and ...[more]

PMID: 31658638

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Project description:UnlabelledBiofilm formation by Candida albicans on medically implanted devices poses a significant clinical challenge. Here, we compared biofilm-associated gene expression in two clinical C. albicans isolates, SC5314 and WO-1, to identify shared gene regulatory responses that may be functionally relevant. Among the 62 genes most highly expressed in biofilms relative to planktonic (suspension-grown) cells, we were able to recover insertion mutations in 25 genes. Twenty mutants had altered biofilm-related properties, including cell substrate adherence, cell-cell signaling, and azole susceptibility. We focused on one of the most highly upregulated genes in our biofilm proles, RHR2, which specifies the glycerol biosynthetic enzyme glycerol-3-phosphatase. Glycerol is 5-fold-more abundant in biofilm cells than in planktonic cells, and an rhr2Δ/Δ strain accumulates 2-fold-less biofilm glycerol than does the wild type. Under in vitro conditions, the rhr2Δ/Δ mutant has reduced biofilm biomass and reduced adherence to silicone. The rhr2Δ/Δ mutant is also severely defective in biofilm formation in vivo in a rat catheter infection model. Expression profiling indicates that the rhr2Δ/Δ mutant has reduced expression of cell surface adhesin genes ALS1, ALS3, and HWP1, as well as many other biofilm-upregulated genes. Reduced adhesin expression may be the cause of the rhr2Δ/Δ mutant biofilm defect, because overexpression of ALS1, ALS3, or HWP1 restores biofilm formation ability to the mutant in vitro and in vivo. Our findings indicate that internal glycerol has a regulatory role in biofilm gene expression and that adhesin genes are among the main functional Rhr2-regulated genes.ImportanceCandida albicans is a major fungal pathogen, and infection can arise from the therapeutically intractable biofilms that it forms on medically implanted devices. It stands to reason that genes whose expression is induced during biofilm growth will function in the process, and our analysis of 25 such genes confirms that expectation. One gene is involved in synthesis of glycerol, a small metabolite that we find is abundant in biofilm cells. The impact of glycerol on biofilm formation is regulatory, not solely metabolic, because it is required for expression of numerous biofilm-associated genes. Restoration of expression of three of these genes that specify cell surface adhesins enables the glycerol-synthetic mutant to create a biofilm. Our findings emphasize the significance of metabolic pathways as therapeutic targets, because their disruption can have both physiological and regulatory consequences.

Project description:Candida albicans is a fungal species that is part of the normal human microbiota and also an opportunistic pathogen capable of causing mucosal and systemic infections. C. albicans cells proliferate in a planktonic (suspension) state, but they also form biofilms, organized and tightly packed communities of cells attached to a solid surface. Biofilms colonize many niches of the human body and persist on implanted medical devices, where they are a major source of new C. albicans infections. Here, we used an unbiased and global substrate-profiling approach to discover proteolytic activities produced specifically by C. albicans biofilms, compared to planktonic cells, with the goal of identifying potential biofilm-specific diagnostic markers and targets for therapeutic intervention. This activity-based profiling approach, coupled with proteomics, identified Sap5 (Candidapepsin-5) and Sap6 (Candidapepsin-6) as major biofilm-specific proteases secreted by C. albicans Fluorogenic peptide substrates with selectivity for Sap5 or Sap6 confirmed that their activities are highly upregulated in C. albicans biofilms; we also show that these activities are upregulated in other Candida clade pathogens. Deletion of the SAP5 and SAP6 genes in C. albicans compromised biofilm development in vitro in standard biofilm assays and in vivo in a rat central venous catheter biofilm model. This work establishes secreted proteolysis as a promising enzymatic marker and potential therapeutic target for Candida biofilm formation. Biofilm formation by the opportunistic fungal pathogen C. albicans is a major cause of life-threatening infections. This work provides a global characterization of secreted proteolytic activity produced specifically by C. albicans biofilms. We identify activity from the proteases Sap5 and Sap6 as highly upregulated during C. albicans biofilm formation and develop Sap-cleavable fluorogenic substrates that enable the detection of biofilms from C. albicans and also from additional pathogenic Candida species. Furthermore, SAP5 and SAP6 deletions confirm that both proteases are required for proper biofilm development in vitro and in vivo We propose that secreted proteolysis is a promising marker for the diagnosis and potential therapeutic targeting of Candida biofilm-associated infections.

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The Synergistic Effect of Zinc Ferrite Nanoparticles Uniformly Deposited on Silver Nanowires for the Biofilm Inhibition of Candida albicans.

Publications

The Synergistic Effect of Zinc Ferrite Nanoparticles Uniformly Deposited on Silver Nanowires for the Biofilm Inhibition of <i>Candida albicans</i>.

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