A mammalian commensal of the oropharyngeal cavity produces antibiotic and antiviral valinomycin in vivo

Abstract Around weaning, piglets are susceptible to infection by bacterial pathobionts, leading to increased morbidity and mortality. We identified isolates of Rothia nasisuis in the upper respiratory tract of weaned healthy piglets that produce valinomycin in vitro and in vivo via its vlm-encoded non-ribosomal peptide synthase (NRPS) enzyme complex. Valinomycin is an antiviral and antibiotic ionophore that shuttles potassium ions across membranes and is capable of inflammasome activation and apoptosis in LPS-primed macrophages at concentrations of 1 uM. Polarized monolayers of epithelial cells were much less sensitive to valinomycin but concentrations ≥ 10 µM decreased trans-epithelial resistance. R. nasisuis inhibited growth of closely related species of Rothia. Deliberate inoculation of valinomycin-producing R. nasisuis into newborn piglets suggested this species can shape the microbiota post weaning. Our findings support the idea that valinomycin is a competitive niche factor potentially also compromising epithelial integrity to gain access to (micro)nutrients.