Bacillus subtilis revives conventional antibiotics against Staphylococcus aureus osteomyelitis

As treatment of Staphylococcus aureus ( S. aureus ) osteomyelitis is often hindered by the development of antibiotic tolerance, novel antibacterial therapeutics are required. Here we found that the cell-free supernatant of Bacillus subtilis ( B. subtilis CFS) killed planktonic and biofilm S. aureus , and increased S. aureus susceptibility to penicillin and gentamicin as well. Further study showed that B. subtilis CFS suppressed the expression of the genes involved in adhesive molecules ( Cna and ClfA ), virulence factor Hla , quorum sensing ( argA , argB and RNAIII ) and biofilm formation ( Ica and sarA ) in S. aureus . Additionally, our data showed that B. subtilis CFS changed the membrane components and increased membrane permeabilization of S. aureus . Finally, we demonstrated that B. subtilis CFS increased considerably the susceptibility of S. aureus to penicillin and effectively reduced S. aureus burdens in a mouse model of implant-associated osteomyelitis. These findings support that B. subtilis CFS may be a potential resistance-modifying agent for β-lactam antibiotics against S. aureus .