Exploring Actinomycetes-derived natural products for activity against Streptococcus suis

Background Streptococcus suis is a major swine pathogen and an emerging zoonotic agent capable of causing severe systemic infections, leading to significant health and economic losses. In recent years, antimicrobial resistance in S. suis has increased substantially, with frequent reports of multidrug-resistant strains driven by extensive antimicrobial use in pig production. This situation is further exacerbated by the role of S. suis as a reservoir of resistance genes within a One Health context. Consequently, there is a growing need for new antimicrobial compounds. Actinomycetes represent a well-known source of bioactive compounds, and the exploration of rare and underexplored taxa offers opportunities to discover novel molecules with unique mechanisms of action. Methods A screening of 800 extracts derived from Actinomycetes was performed against two virulent S. suis strains to evaluate antimicrobial activity. Extracts showing inhibitory effects were further subjected to fractionation by chromatography to isolate and characterize active components. Subsequent analyses focused on identifying fractions with inhibitory activity against the target strains using high-resolution mass spectrometry. Results The initial screening identified numerous Actinomycetes -derived extracts with inhibitory activity against S. suis , including extracts with activity against one or both strains. Based on activity spectrum and taxonomic origin, nine extracts were selected for further analysis. Fractionation enabled the identification of active fractions with consistent inhibitory effects against both strains. Compound characterization revealed bioactive molecules related to verucopeptin, hydroxyrifamycin and thiopeptides. In one extract, the active compound could not be identified, with analysis suggesting a complex composition of its active fraction. Conclusions These findings support Actinomycetes as a valuable source of novel antimicrobials against S. suis. The identified bioactive molecules further emphasize the potential of underexplored microbes for the discovery and development of novel antimicrobials, especially relevant in the context of increasing antimicrobial resistance.