Dataset Information

The mPEG-PCL Copolymer for Selective Fermentation of Staphylococcus lugdunensis Against Candida parapsilosis in the Human Microbiome.

ABSTRACT: Many human skin diseases, such as seborrheic dermatitis, potentially occur due to the over-growth of fungi. It remains a challenge to develop fungicides with a lower risk of generating resistant fungi and non-specifically killing commensal microbes. Our probiotic approaches using a selective fermentation initiator of skin commensal bacteria, fermentation metabolites or their derivatives provide novel therapeutics to rein in the over-growth of fungi. Staphylococcus lugdunensis (S. lugdunensis) bacteria and Candida parapsilosis (C. parapsilosis) fungi coexist in the scalp microbiome. S. lugdunensis interfered with the growth of C. parapsilosis via fermentation. A methoxy poly(ethylene glycol)-b-poly(?-caprolactone) (mPEG-PCL) copolymer functioned as a selective fermentation initiator of S. lugdunensis, selectively triggering the S. lugdunensis fermentation to produce acetic and isovaleric acids. The acetic acid and its pro-drug diethyleneglycol diacetate (Ac-DEG-Ac) effectively suppressed the growth of C. parapsilosis in vitro and impeded the fungal expansion in the human dandruff. We demonstrate for the first time that S. lugdunensis is a skin probiotic bacterium that can exploit mPEG-PCL to yield fungicidal short-chain fatty acids (SCFAs). The concept of bacterial fermentation as a part of skin immunity to re-balance the dysbiotic microbiome warrants a novel avenue for studying the probiotic function of the skin microbiome in promoting health.

SUBMITTER: Kao MS

PROVIDER: S-EPMC5243119 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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The mPEG-PCL Copolymer for Selective Fermentation of Staphylococcus lugdunensis Against Candida parapsilosis in the Human Microbiome.

Kao Ming-Shan MS Wang Yanhan Y Marito Shinta S Huang Stephen S Lin Wan-Zhen WZ Gangoiti Jon A JA Barshop Bruce A BA Hyun Choi C Lee Woan-Ruah WR Sanford James A JA Gallo Richard L RL Ran Yuping Y Chen Wan-Tzu WT Huang Chun-Jen CJ Hsieh Ming-Fa MF Huang Chun-Ming CM

Journal of microbial & biochemical technology 20160619 4

Many human skin diseases, such as seborrheic dermatitis, potentially occur due to the over-growth of fungi. It remains a challenge to develop fungicides with a lower risk of generating resistant fungi and non-specifically killing commensal microbes. Our probiotic approaches using a selective fermentation initiator of skin commensal bacteria, fermentation metabolites or their derivatives provide novel therapeutics to rein in the over-growth of fungi. <i>Staphylococcus lugdunensis</i> (<i>S. lugdu ...[more]

PMID: 28111598

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Project description:Fatal Candida albicans infections in the mucosal system can occur in association with immune-compromised diseases and dysbacteriosis. Currently, amphotericin B (AmB) is considered to be the most effective antibiotic in the treatment of C. albicans infections, but its clinical application is limited by side effects and poor bioavailability. In order to use AmB in the local treatment of oral C. albicans infections, AmB/MPEG-PCL-g-PEI (monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone)-graft-polyethylenimine, MPP) micelles were prepared. A series of characterizations were performed. The micelles allowed a sustained in vitro release in both normal oral conditions (pH 6.8) and C. albicans infection conditions (pH 5.8). Then, buccal tablets containing freeze-dried powder of AmB/MPP micelles were produced by direct compression process and evaluated as regards to weight variation, hardness, and friability. In vitro drug release of the buccal tablets was measured in both the United States Pharmacopeia dissolution apparatus and the dissolution rate test apparatus, which was previously designed for simulating in vivo conditions of the oral cavity. The buccal tablets could sustainably release within 8 h and meet the antifungal requirements. Regarding safety assessment of AmB/MPP micelles, in vivo histopathological data showed no irritation toward buccal mucosa of the rats in both optical microscopy and ultrastructure observation of the tissues. MTT experiment proved that AmB/MPP micelles reduced the cytotoxicity of AmB. The micelles delivered through the gastrointestinal route were also found to be non-systemic toxicity by liquid chromatography-mass spectrometry analysis. Furthermore, the antifungal action of AmB/MPP micelles was evaluated. Although AmB/MPP had no obvious improvement as compared to AmB alone in the antifungal effect on planktonic C. albicans, the micelles significantly enhanced the antifungal activity against the biofilm state of C. albicans. Thus, it was concluded that AmB/MPP micelles represent a promising novel drug delivery system for the local treatment of oral C. albicans infections.

Dataset Information

The mPEG-PCL Copolymer for Selective Fermentation of Staphylococcus lugdunensis Against Candida parapsilosis in the Human Microbiome.

Publications

The mPEG-PCL Copolymer for Selective Fermentation of Staphylococcus lugdunensis Against Candida parapsilosis in the Human Microbiome.

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