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Antimicrob Agents Chemother. 2019 Mar 27;63(4). pii: e02009-18. doi: 10.1128/AAC.02009-18. Print 2019 Apr.

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

Author information

1
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
2
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea wbpark1@snu.ac.kr.

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.

KEYWORDS:

SAL200; Staphylococcus aureus ; mice; phage endolysin; pneumonia

PMID:
30670417
PMCID:
PMC6437543
[Available on 2019-09-27]
DOI:
10.1128/AAC.02009-18

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