RESUMEN

Clostridioides difficile spores produced during infection are important for the recurrence of the disease. Here, we show that C. difficile spores gain entry into the intestinal mucosa via pathways dependent on host fibronectin-α5ß1 and vitronectin-αvß1. The exosporium protein BclA3, on the spore surface, is required for both entry pathways. Deletion of the bclA3 gene in C. difficile, or pharmacological inhibition of endocytosis using nystatin, leads to reduced entry into the intestinal mucosa and reduced recurrence of the disease in a mouse model. Our findings indicate that C. difficile spore entry into the intestinal barrier can contribute to spore persistence and infection recurrence, and suggest potential avenues for new therapies.

Asunto(s)

Clostridioides difficile/fisiología , Infecciones por Clostridium/microbiología , Células Epiteliales/microbiología , Células Epiteliales/patología , Intestinos/microbiología , Intestinos/patología , Esporas Bacterianas/fisiología , Animales , Adhesión Bacteriana/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Línea Celular , Clostridioides difficile/efectos de los fármacos , Clostridioides difficile/ultraestructura , Colágeno/metabolismo , Endocitosis , Células Epiteliales/ultraestructura , Femenino , Fibronectinas/metabolismo , Humanos , Integrinas/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Masculino , Ratones Endogámicos C57BL , Nistatina/farmacología , Unión Proteica/efectos de los fármacos , Recurrencia , Esporas Bacterianas/efectos de los fármacos , Esporas Bacterianas/ultraestructura , Ácido Taurocólico/farmacología , Vitronectina/metabolismo