Novel antibody-antibiotic conjugate using KRM-1657 as payload eliminates intracellular MRSA in vitro and in vivo.
Bioorg Chem
; 150: 107532, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38852312
ABSTRACT
Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S.aureus within host cells may cause long-term colonization and clinical failure. Current treatments have poor efficacy in clearing intracellular bacteria. Antibody-antibiotic conjugates (AACs) is a novel strategy for eliminating intracellular bacteria. Herein, we use KRM-1657 as payload of AAC for the first time, and we conjugate it with anti S. aureus antibody via a dipeptide linker (Valine-Alanine) to obtain a novel AAC (ASAK-22). The ASAK-22 exhibits good in vitro pharmacokinetic properties and inhibitory activity against intracellular MRSA, with 100 µg/mL of ASAK-22 capable of eliminating intracellular MRSA to the detection limit. Furthermore, the in vivo results demonstrate that a single administration of ASAK-22 significantly reduces the bacterial burden in the bacteremia model, which is superior to the vancomycin treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Testes de Sensibilidade Microbiana
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Staphylococcus aureus Resistente à Meticilina
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Antibacterianos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Chem
/
Bioorganic chem
/
Bioorganic chemistry
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China