AP183 Inhibits Biofilm Formation and Proliferation in Murine and Bovine Disease Models.

The increasing frequency of antimicrobial resistance has spurred interest in identifying alternative therapeutants. We investigated the inhibitory capacity of strains in mouse and bovine models. Among multiple strains that inhibited growth , AP183 provided the most potent inhibition of proliferation and bioluminescence in a mouse cutaneous wound ( = 0.02). Histology revealed abundant Gram-positive cocci in control wounds that were reduced in AP183-treated tissues. Experiments were then conducted to evaluate the ability of AP183 to prevent biofilm formation on a tracheostomy tube substrate. AP183 could form a biofilm on a tracheostomy tube inner cannula substrate, and that this biofilm was antagonistic to colonization. AP183 was also observed to inhibit the growth of isolates originated from bovine mastitis cases. To evaluate the inflammatory response of mammary tissue to intramammary inoculation with AP183, we used high dose and low dose inocula in dairy cows. At the high dose, a significant increase in somatic cell count (SCC) and clinical mastitis was observed at all post-inoculation time points ( < 0.01), which resolved quickly compared to induced mastitis; in contrast, the lower dose of AP183 resulted in a slight increase of SCC and no clinical mastitis. In a subsequent experiment, all mammary quarters in four cows were induced to have grade 1 clinical mastitis by intramammary inoculation of a mastitis isolate; following mastitis induction, eight quarters were treated with AP183 and milk samples were collected from pretreatment and post-treatment samples for 9 days. In groups treated with AP183, SCC and abundance of decreased with significant reductions in after 3 days post-inoculation with AP183 ( = 0.04). A milk microbiome analysis revealed significant reductions in relative abundance in the AP183-treated group by 8 days post-inoculation ( = 0.02). These data indicate that AP183 can inhibit biofilm formation and its proliferation in murine and bovine disease models.