Abstract
The increasing frequency of
S. aureus
antimicrobial resistance has spurred interest in identifying alternative therapeutants. We investigated the
S. aureus-
inhibitory capacity of
B. velezensis
strains in mouse and bovine models. Among multiple
B. velezensis
strains that inhibited
S. aureus
growth
in vitro
,
B. velezensis
AP183 provided the most potent inhibition of
S. aureus
proliferation and bioluminescence in a mouse cutaneous wound (
P
= 0.02). Histology revealed abundant Gram-positive cocci in control wounds that were reduced in
B. velezensis
AP183-treated tissues. Experiments were then conducted to evaluate the ability of
B. velezensis
AP183 to prevent
S. aureus
biofilm formation on a tracheostomy tube substrate.
B. velezensis
AP183 could form a biofilm on a tracheostomy tube inner cannula substrate, and that this biofilm was antagonistic to
S. aureus
colonization.
B. velezensis
AP183 was also observed to inhibit the growth of
S. aureus
isolates originated from bovine mastitis cases. To evaluate the inflammatory response of mammary tissue to intramammary inoculation with
B. velezensis
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 (
P
< 0.01), which resolved quickly compared to
S. aureus-
induced mastitis; in contrast, the lower dose of
B. velezensis
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
S. aureus
mastitis isolate; following mastitis induction, eight quarters were treated with
B. velezensis
AP183 and milk samples were collected from pretreatment and post-treatment samples for 9 days. In groups treated with
B. velezensis
AP183, SCC and abundance of
S. aureus
decreased with significant reductions in
S. aureus
after 3 days post-inoculation with AP183 (
P
= 0.04). A milk microbiome analysis revealed significant reductions in
S. aureus
relative abundance in the AP183-treated group by 8 days post-inoculation (
P
= 0.02). These data indicate that
B. velezensis
AP183 can inhibit
S. aureus
biofilm formation and its proliferation in murine and bovine disease models.