Identification of ShgH as a dual histidine/glutamine transporter component essential for Streptococcus suis virulence and biofilm modulation

García, Carla (Universidad de Zaragoza) ; Saralegui, Luis (Universidad de Zaragoza) ; Morales, Beatriz ; Jurado, Paula ; Bes, M. Teresa (Universidad de Zaragoza) ; Marín, Clara ; Arenas, Jesús (Universidad de Zaragoza)

Resumen: Streptococcus suis is a zoonotic pathogen that affects pigs and humans. In this study, we characterised ShgH, a predicted substrate-binding component of an ABC transporter. Immunoassays confirmed that ShgH is expressed, secreted and surface-exposed in S. suis, in agreement with its proposed transporter function. Isothermal titration calorimetry demonstrated that ShgH binds glutamine and histidine, with a higher affinity for histidine. Deletion of the shgH gene significantly impaired uptake of both radiolabelled amino acids confirming its role as part of a transporter. Functional analysis revealed that shgH deletion results in a marked reduction in virulence in a murine infection model, while host colonization remained unaffected. ShgH contributes to infection by facilitating evasion of phagocytosis and resistance to oxidative stress through impaired nutrient acquisition and reduced capsule production. In addition, ShgH regulates biofilm formation and architecture. Notably, ShgH is highly conserved among pathogenic streptococci, suggesting a broader functional relevance. Altogether, our findings identify ShgH as a dual glutamine/histidine- binding protein essential for nutrient uptake and virulence in S. suis, and a promising target for future therapeutic interventions.

Idioma: Inglés

DOI: 10.1016/j.micres.2025.128354

Año: 2025

Publicado en: MICROBIOLOGICAL RESEARCH 302 (2025), 128354
ISSN: 0944-5013

Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI PID2020-114617RB-100

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)