Staphylococcus hominis daptide antibiotics, derivatives thereof, and methods of treatment

The development of hominicin, a daptide antibiotic with specific modifications, addresses the need for new antibiotics by effectively targeting Staphylococcal skin bacteria and Streptococcus pyogenes through membrane pore formation, offering a treatment for skin conditions.

WO2025240758A1 Publication Date: 2025-11-20THE REGENTS OF THE UNIVERSITY OF COLORADO
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Patent Information

Application Number
PCT/US2025/029592
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-05-15
Filing Date
2025-05-15
Publication Date
2025-11-20

AI Technical Summary

Technical Problem

There is a need for new antibiotics and compositions to address the rise of multi-drug-resistant bacteria, particularly focusing on Staphylococcus aureus and Streptococcus pyogenes, and a lack of understanding about the mechanism of action and resistance to daptides, a recently discovered class of ribosomally-synthesized and post-translationally-modified peptides.

Method used

Development of a novel daptide antibiotic, hominicin, with specific amino acid modifications, including a dimethylated N-terminus and a Dmp-modified C-terminus, which exhibits broad activity against Staphylococcal skin bacteria and Streptococcus pyogenes by forming pores in the bacterial cytoplasmic membrane, and the identification of HomI as a resistance determinant.

Benefits of technology

Hominicin demonstrates effective antimicrobial activity against Staphylococcal skin bacteria and Streptococcus pyogenes, reducing skin colonization and cutaneous injury in murine models, providing a potential treatment for skin conditions.

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Abstract

Embodiments of the present disclosure generally relate to a new class of daptide antibiotics and compositions that include the daptide antibiotics. Embodiments described herein also generally relate to methods of treating various diseases or medical conditions in a patient utilizing the new class of daptide antibiotics and compositions thereof. In an embodiment, a composition for treating a skin condition in a patient is provided. The composition includes a daptide comprising: a dimethylated 7V-terminus; a Dmp-modified C- terminus; a dehydrobutyrine residue positioned between the dimethylated 7V-terminus and the Dmp-modified C-terminus; at least one alanine (A) residue or at least one dehydroalanine (Dha) residue positioned between the dimethylated 7V-terminus and the Dmp-modified C- terminus; and at least one amino acid residue positioned between the dimethylated 7V-terminus and the Dmp-modified C-terminus. In another embodiment is provided a daptide bacteriocin composition that is antimicrobial against a staphylococcal skin bacteria in a patient.
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