Efficacy of Intranasal Administration of the Recombinant Endolysin SAL200 in a Lethal Murine Staphylococcus aureus Pneumonia Model.

Abstract

SAL200 is derived from a phage endolysin and is a novel candidate drug for the treatment of Staphylococcus aureus infection. We investigated the efficacy of the recombinant endolysin SAL200 in a lethal murine pneumonia model. Lethal pneumonia was established by intranasally administering a methicillin-susceptible (Newman) or methicillin-resistant (LAC) S. aureus strain into BALB/c mice. The mice were treated with a single intranasal administration of SAL200 or phosphate-buffered saline at 2 h after S. aureus infection. The survival rates were recorded until 60 h after the bacterial challenge. The bacterial loads in the lungs and blood, histopathology of lung tissues, and serum cytokine levels were evaluated following the S. aureus challenge. The SAL200-treated group and control group exhibited 90% to 95% and 10% to 40% survival rates, respectively. The bacterial loads in the lungs of the SAL200-treated group were significantly lower by ∼10-fold than those of the control group as early as 1 h after treatment. Histopathologic recovery of pneumonia was observed in the SAL200-treated mice. The cytokine levels were comparable between groups. These results suggest that direct administration of SAL200 into the lungs could be a potential adjunct treatment against severe pneumonia caused by S. aureus.

• Authors: Ji Yun Bae, Kang Il Jun, Chang Kyung Kang, Kyoung-Ho Song, Pyoeng Gyun Choe, Ji-Hwan Bang, Eu Suk Kim, Sang Won Park, Hong Bin Kim, Nam-Joong Kim, Wan Beom Park, Myoung-Don Oh
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 63 Issue 4 (04 2019) ISSN: 1098-6596 [Electronic] United States
• PMID: 30670417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American Society for Microbiology.

Chemical References

• Anti-Bacterial Agents
• Cytokines
• Endopeptidases
• endolysin

Topics

• Administration, Intranasal
• Animals
• Anti-Bacterial Agents (therapeutic use)
• Bacterial Load (drug effects)
• Cytokines (blood)
• Disease Models, Animal
• Endopeptidases (therapeutic use)
• Female
• Mice
• Mice, Inbred BALB C
• Pneumonia, Staphylococcal (drug therapy, mortality)
• Staphylococcus aureus (drug effects)