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Published on: May 5, 2016
Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its
Lulu Zhang1,2, Bo Wen1, Mei Bao1,2
1Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant pathogen threatening human health and safety. Biofilms are an important cause of its drug resistance and pathogenicity. Inhibition and elimination of biofilms is an important strategy for the treatment of MRSA infection. Andrographolide sulfonate (AS) is an active component of the traditional herbal medicine Andrographis paniculata. This study aims to explore the inhibitory effect and corresponding mechanisms of AS on MRSA and its biofilms. Three doses of AS (6.25, 12.5, and 25 mg/ml) were introduced to MRSA with biofilms. In vitro antibacterial testing and morphological observation were used to confirm the inhibitory effect of AS on MRSA with biofilms. Real-time PCR and metabonomics were used to explore the underlying mechanisms of the effect by studying the expression of biofilm-related genes and endogenous metabolites. AS displayed significant anti-MRSA activity, and its minimum inhibitory concentration was 50 μg/ml. Also, AS inhibited biofilms and improved biofilm permeability. The mechanisms are mediated by the inhibition of the expression of genes, such as quorum sensing system regulatory genes (agrD and sarA), microbial surface components-recognizing adhesion matrix genes (clfA and fnbB), intercellular adhesion genes (icaA, icaD, and PIA), and a gene related to cellular eDNA release (cidA), and the downregulation of five biofilm-related metabolites, including anthranilic acid, D-lactic acid, kynurenine, L-homocitrulline, and sebacic acid. This study provided valuable evidence for the activity of AS against MRSA and its biofilms and extended the methods to combat MRSA infection.
Insights
Andrographolide sulfonate (AS) effectively inhibits Methicillin-resistant Staphylococcus aureus (MRSA) biofilms by downregulating key genes and metabolites. This natural compound offers a promising strategy for combating drug-resistant bacterial infections.
Area of Science:
- Microbiology
- Pharmacology
- Natural Products Chemistry
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat due to its drug resistance, often exacerbated by biofilm formation.
- Biofilms contribute to MRSA's pathogenicity and resistance, necessitating strategies for their inhibition and elimination.
- Andrographolide sulfonate (AS), derived from the traditional herb Andrographis paniculata, is explored for its therapeutic potential.
Purpose of the Study:
- To investigate the inhibitory effects of Andrographolide sulfonate (AS) on MRSA and its biofilms.
- To elucidate the underlying molecular mechanisms by which AS affects MRSA biofilm formation and gene expression.
Main Methods:
- In vitro antibacterial assays and morphological observations were employed to assess AS efficacy against MRSA biofilms.
- Real-time PCR was utilized to analyze the expression of critical biofilm-related genes.
- Metabonomic profiling was conducted to identify changes in endogenous metabolites influenced by AS treatment.
Main Results:
- AS demonstrated significant antibacterial activity against MRSA, with a minimum inhibitory concentration of 50 μg/ml.
- AS effectively inhibited MRSA biofilm formation and enhanced biofilm permeability.
- AS treatment led to the downregulation of genes involved in quorum sensing (agrD, sarA), adhesion (clfA, fnbB), intercellular adhesion (icaA, icaD, PIA), and eDNA release (cidA).
- Five key biofilm-related metabolites, including anthranilic acid and D-lactic acid, were downregulated by AS.
Conclusions:
- Andrographolide sulfonate exhibits potent anti-MRSA and anti-biofilm activity.
- The mechanisms involve the modulation of crucial gene expression and metabolic pathways related to biofilm formation.
- AS represents a promising natural compound for developing novel therapeutic strategies against MRSA infections.
