Transthyretin is a novel innate immune effector against Gram negative bacteria

Pseudomonas aeruginosa is an opportunistic pathogen that frequently causes severe bloodstream and respiratory infections, yet the interactions between this bacterium and the innate immune system remain poorly investigated. In this study we identified transthyretin, the transporter protein of thyroid...

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Detalles Bibliográficos
Autores: Bernabé Rodríguez, Tania, Verd, María, Ramis, Guillem, Gonzalez-Alsina, Alex, Qadi, Mohammad, Mateu-Borrás, Margalida, Doménech-Sánchez, Antonio, Alberti, Sebastian
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:dnet:docusalut___::903ae88afa388f019a689377c54d8e30
Acceso en línea:https://hdl.handle.net/20.500.13003/27173
Access Level:acceso abierto
Palabra clave:Gram-Negative Bacteria
Humans
Immunity, Innate
Lipopolysaccharides
Prealbumin
Pseudomonas Infections
Pseudomonas aeruginosa
Bacterias Gramnegativas
Humanos
Inmunidad Innata
Lipopolisacáridos
Prealbúmina
Infecciones por Pseudomonas
Descripción
Sumario:Pseudomonas aeruginosa is an opportunistic pathogen that frequently causes severe bloodstream and respiratory infections, yet the interactions between this bacterium and the innate immune system remain poorly investigated. In this study we identified transthyretin, the transporter protein of thyroid hormone and retinol, as a novel binding partner of the bacterium. We show that transthyretin binds to lipopolysaccharide via lipid A. Transthyretin binding induces the agglutination of transthyretin-bacteria complexes and a reduction in bacterial viability. Mapping studies reveal that the N-terminal region of transthyretin mediates bacterial interaction, and a synthetic peptide derived from this domain exhibits potent bactericidal activity against a broad collection of P. aeruginosa isolates as well as other Gram-negative bacteria by disrupting membrane integrity. These findings identify transthyretin as an endogenous antimicrobial factor and uncover cryptic antimicrobial activity within its N-terminal region. Beyond extending the functional repertoire of transthyretin, these results suggest a novel role for this protein in innate defense.