Hyaluronic acid binding peptides enhance host defense...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 7/08 (2006.01) A61K 38/10 (2006.01) A61P 31/04 (2006.01)

Patent

CA 2610791

Several species of bacteria capable of invasive infections, such as S. pyogenes, S. equi and P. multocida, contain hyaluronic acid (HA) in their capsules. Bacterial species such as Staphylococcus aureus and related Staphylococci have capsules that contain acidic polysaccharides. Bacterial capsule or bacterial surface binding peptides were synthesized and tested in a culture model of invasive bacterial infections, specifically translocation through polarized keratinocyte cultures. The peptides reduced the translocation of a variety of bacterial species, with a concomitant increase in bacterial internalization by the keratinocytes. In vivo, subcutaneous inoculation of encapsulated GAS treated with peptides delayed bacterial dissemination. In a mouse surgical wound model infected with S. aureus, treatment with peptides reduced the numbers of bacteria and inflammation at the wound site.

De nombreuses espèces de bactéries capables de provoquer des infections invasives, notamment S. pyogenes, S. equi et P. multocida, contiennent de l'acide hyaluronique (HA) dans leurs capsules. Les espèces de bactéries, notamment la Staphylococcus aureus et la Staphylococcie afférente, possèdent des capsules qui renferment des polysaccharides acides. Les peptides de liaison à la capsule bactérienne ou à la surface bactérienne ont été synthétisés et testés dans un modèle de culture d'infections bactériennes invasives, particulièrement la translocation à l'aide de cultures de kératinocytes polarisés. Les peptides ont permis une diminution de la translocation de diverses espèces bactériennes, et une augmentation concomitante de l'internalisation bactérienne par les kératinocytes. In vivo, l'inoculation sous-cutanée de GAS encapsulés traités par peptides à retardé la dissémination bactérienne. Sur un modèle de plaie chirurgicale de souris infectée par S. aureus, le traitement par peptides a permis de réduire le nombre de bactéries et de diminuer l'inflammation de la plaie.

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