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Compositions and methods for treating and/or preventing pathogenic fungal infection and for maintenance of microbiome commensalism

A composition, pathogenic technology, applied in the direction of chemical instruments and methods, antifungal agents, pharmaceutical formulations, etc., can solve problems such as excessive and invasive

Pending Publication Date: 2020-01-31
UNIVERSITY OF CHICAGO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these same C. albicans species can switch from growth in a harmless yeast form to a toxic mycelial form that is invasive and overgrows to produce a high fungal load that causes disease

Method used

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  • Compositions and methods for treating and/or preventing pathogenic fungal infection and for maintenance of microbiome commensalism
  • Compositions and methods for treating and/or preventing pathogenic fungal infection and for maintenance of microbiome commensalism
  • Compositions and methods for treating and/or preventing pathogenic fungal infection and for maintenance of microbiome commensalism

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0179] Materials and methods

[0180] Animals and Candida challenge models

[0181] All animal experiment protocols were approved by the IACUC at the University of Chicago. Animals were wild-type (WT) or PYY bred on a C57Bl / 6 background - / - Gene-deficient mice and were housed under standard 12:12 light / dark conditions at the University of Chicago. Maintain sterile animals in sterile isolators in our aseptic facility. For studies using Candida spp., animals were maintained in individual BSL2 cages and treated with oral Candida belongs to Clindamycin (PO gavage, 25 mg) and cefoxitin (IM, 50 mg) were administered 2 days prior to challenge. One day before challenge, mice were fasted and administered clindamycin (25 mg) and cortisone acetate (SQ). Mice were gavaged with 200 uL of 1.0 OD600 C. albicans (sc3514) in the morning and provided food 4 hours later. Clindamycin (250 mg / kg BW) was administered on days 0, 2, 4, 6 and 8 until sacrifice. In studies examining oral peptid...

Embodiment 2

[0215] It is envisaged that PYY prevents C. albicans biofilm formation by intercalating into the membranes at the tips of C. albicans hyphae and subsequently permeabilizing these membranes by forming pores, and that the amphipathic nature of the α-helix is ​​important for the formation of this pore. Therefore, AVpeptides 9-11, 23 and 25 (SEQ ID NO: 15-17, 29 and 31) were designed to remove polar or charged amino acid residues from the hydrophobic face and replace them with non-polar residues. Increase the hydrophobic moment of the α-helix ( Figure 12 ). Experiments performed during the development of the embodiments herein showed that these peptides were 13-36 The concentration of Candida albicans greatly inhibited the biofilm formation. The antifungal activity of the peptides described in this application was tested by performing a crystal violet based biofilm assay. In this assay, C. albicans was induced to form biofilms in 96-well plates in the presence or absence of pe...

Embodiment 3

[0244] Experiments were carried out during the development of the embodiments herein to demonstrate the use of PYY-based peptides as prophylactic or therapeutic agents for drug-resistant strains of Candida albicans ( Figure 14 ).

[0245] References

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Abstract

Provided herein are compositions and methods for treating and / or preventing pathogenic fungal infection and for maintenance of microbiome commensalism. In particular, provided herein are compositionscomprising modified peptide YY (PYY) peptides and therapeutic and / or prophylactic methods of use thereof.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application Serial No. 62 / 506,902, filed May 16, 2017, and U.S. Provisional Patent Application Serial No. 62 / 581,358, filed November 3, 2017, both U.S. Provisional Patent Applications Serial numbers are hereby incorporated by reference in their entirety. [0003] Statement Regarding Federal Funds [0004] This invention was made with government support under DK042086, DK113788, and DK105728 awarded by the National Institutes of Health. The government has certain rights in this invention. technical field [0005] Provided herein are compositions and methods for treating and / or preventing pathogenic fungal infections and maintaining microbiota symbiosis. In particular, provided herein are compositions comprising modified Peptide YY (PYY) peptides and methods of their therapeutic and / or prophylactic use. [0006] technical background [0007] A healthy human g...

Claims

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Application Information

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IPC IPC(8): C07K14/575A61K38/16
CPCC07K14/723A61K38/1796A61P31/10A61K45/06C07K14/72
Inventor E·B·张J·F·皮埃尔K·A·哈里斯
Owner UNIVERSITY OF CHICAGO
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