Use of the Antimicrobial Peptide Sublancin with Combined Antibacterial and Immunomodulatory Activities To Protect against Methicillin-Resistant Staphylococcus aureus Infection in Mice

Methicillin-resistant Staphylococcus aureus (MRSA) is the major pathogen causing serious hospital infections worldwide. With the emergence and rapid spread of drug-resistant bacteria, there is extraordinary interest in antimicrobial peptides (AMPS) as promising candidates for the treatment of antibiotic-resistant bacterial infections. Sublancin, a glycosylated AMP produced by Bacillus subtilis 168, has been reported to possess protective activity against bacterial infection. This study was performed to evaluate the efficacy of sublancin in the prevention of MRSA ATCC43300 intraperitoneal infection in mice. We determined that sublancin had a minimal inhibitory concentration of 15 mu M against MRSA ATCC43300. The antimicrobial action of sublancin involved the destruction of the bacterial cell wall. Dosing of mice with sublancin greatly alleviated (p < 0.05) the bacterial burden caused by MRSA intraperitoneal infection and considerably reduced the mortality and weight loss (19.2 +/- 0.62 g vs 20.6 +/- 0.63 g for MRSA vs 2.0 mg/kg sublancin, respectively, on day 3) of MRSA-challenged mice (p < 0.05). Sublancin was further found to balance the immune response during infection and relieve intestinal inflammation through inhibition of NF-kappa B activation (p < 0.01). With their combined antibacterial and immunomodulatory activities, sublancin may have potent therapeutic potential for drug-resistant infections and sepsis.