RESUMEN
Staphylococcus aureus is a predominant cause of chronic lung infections. While the airway environment is rich in highly sialylated mucins, the interaction of S. aureus with sialic acid is poorly characterized. Using S. aureus USA300 as well as clinical isolates, we demonstrate that quorum-sensing dysfunction, a hallmark of S. aureus adaptation, correlates with a greater ability to consume free sialic acid, providing a growth advantage in an air-liquid interface model and in vivo. Furthermore, RNA-seq experiment reveals that free sialic acid triggers transcriptional reprogramming promoting S. aureus chronic lifestyle. To support the clinical relevance of our results, we show the co-occurrence of S. aureus, sialidase-producing microbiota and free sialic acid in the airway of patients with cystic fibrosis. Our findings suggest a dual role for sialic acid in S. aureus airway infection, triggering virulence reprogramming and driving S. aureus adaptive strategies through the selection of quorum-sensing dysfunctional strains.
Asunto(s)
Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Percepción de Quorum/genética , Ácido N-Acetilneuramínico , Sistema Respiratorio , Proteínas BacterianasAsunto(s)
Enfermedades Inflamatorias del Intestino , Mucinas , Humanos , Mucinas/metabolismo , Glicosilación , PolisacáridosRESUMEN
For the first time, fecal mucins of Crohn's disease patients were analyzed by mass spectrometry. Compared with control subjects, Crohn's disease patients showed a significant decrease in sialylated glycans that we propose as new noninvasive tool for screening of intestinal diseases.
