Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus.

Abstract

Pneumonia is one of the most prevalent Staphylococcus aureus-mediated diseases, and the treatment of this infection is becoming challenging due to the emergence of multidrug-resistant S. aureus, especially methicillin-resistant S. aureus (MRSA) strains. It has been reported that LysGH15, the lysin derived from phage GH15, displays high efficiency and a broad lytic spectrum against MRSA and that apigenin can markedly diminish the alpha-hemolysin of S. aureus. In this study, the combination therapy of LysGH15 and apigenin was evaluated in vitro and in a mouse S. aureus pneumonia model. No mutual adverse influence was detected between LysGH15 and apigenin in vitro. In animal experiments, the combination therapy showed a more effective treatment effect than LysGH15 or apigenin monotherapy (P < 0.05). The bacterial load in the lungs of mice administered the combination therapy was 1.5 log units within 24 h after challenge, whereas the loads in unprotected mice or mice treated with apigenin or LysGH15 alone were 10.2, 4.7, and 2.6 log units, respectively. The combination therapy group showed the best health status, the lowest ratio of wet tissue to dry tissue of the lungs, the smallest amount of total protein and cells in the lung, the fewest pathological manifestations, and the lowest cytokine level compared with the other groups (P < 0.05). With regard to its better protective efficacy, the combination therapy of LysGH15 and apigenin exhibits therapeutic potential for treating pneumonia caused by MRSA. This paper reports the combination therapy of lysin and natural products derived from traditional Chinese medicine.

• Authors: Feifei Xia, Xin Li, Bin Wang, Pengjuan Gong, Feng Xiao, Mei Yang, Lei Zhang, Jun Song, Liyuan Hu, Mengjun Cheng, Changjiang Sun, Xin Feng, Liancheng Lei, Songying Ouyang, Zhi-Jie Liu, Xinwei Li, Jingmin Gu, Wenyu Han
• Journal: Applied and environmental microbiology (Appl Environ Microbiol) Vol. 82 Issue 1 Pg. 87-94 (01 01 2016) ISSN: 1098-5336 [Electronic] United States
• PMID: 26475103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Anti-Bacterial Agents
• Viral Proteins
• Apigenin

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage)
• Apigenin (administration & dosage)
• Disease Models, Animal
• Drug Therapy, Combination
• Female
• Humans
• Mice
• Mice, Inbred C57BL
• Pneumonia (drug therapy, microbiology)
• Staphylococcal Infections (drug therapy, microbiology)
• Staphylococcus Phages (chemistry, enzymology)
• Staphylococcus aureus (drug effects, physiology)
• Viral Proteins (administration & dosage)