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

Feifei Xia1, Xin Li1, Bin Wang1

  • 1Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, People's Republic of China.

Applied and Environmental Microbiology
|October 18, 2015
PubMed

Insights

This study shows that combining LysGH15 (a phage lysin) and apigenin effectively treats methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in mice. This combination therapy significantly reduces bacterial load and improves health outcomes compared to single treatments.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Pneumonia caused by Staphylococcus aureus, particularly multidrug-resistant strains like MRSA, presents significant treatment challenges.
  • LysGH15, a phage-derived lysin, demonstrates broad-spectrum efficacy against MRSA.
  • Apigenin, a natural compound, has shown potential in reducing S. aureus alpha-hemolysin production.

Purpose of the Study:

  • To evaluate the in vitro and in vivo efficacy of a combination therapy using LysGH15 and apigenin for treating MRSA-induced pneumonia.
  • To assess potential adverse interactions between LysGH15 and apigenin.
  • To compare the therapeutic effects of the combination therapy against monotherapies with LysGH15 or apigenin.

Main Methods:

  • In vitro assessment for mutual adverse effects between LysGH15 and apigenin.
  • Establishment of a mouse model of S. aureus pneumonia for in vivo evaluation.
  • Administration of combination therapy, monotherapies, or no treatment to infected mice.
  • Quantification of bacterial load in lung tissue.
  • Assessment of lung tissue pathology, including wet-to-dry ratio, protein and cell counts, and cytokine levels.

Main Results:

  • No adverse interactions were observed between LysGH15 and apigenin in vitro.
  • Combination therapy significantly outperformed LysGH15 or apigenin monotherapy in reducing bacterial load in the lungs (1.5 log units vs. 2.6 and 4.7 log units, respectively).
  • The combination therapy group exhibited improved health status, reduced lung inflammation (lower wet/dry ratio, protein, and cell counts), and decreased cytokine levels compared to monotherapy groups and controls.

Conclusions:

  • The combination of LysGH15 and apigenin demonstrates significant therapeutic potential for treating MRSA-induced pneumonia.
  • This synergistic approach offers a promising alternative to conventional antibiotic treatments for challenging MRSA infections.
  • The study highlights the value of combining phage-derived lysins with natural products for novel antimicrobial strategies.

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