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Published on: December 27, 2016
Inhibition of Staphylococcus aureus biofilm formation by gurmarin, a plant-derived cyclic peptide
Adeline W Chang1, Scot E Dowd2, Gordon Brackee3
1Division of Biology, Kansas State University, Manhattan, KS, United States.
Abstract:
Staphylococcus aureus (Sa) is an opportunistic pathogen capable of causing various infections ranging from superficial skin infections to life-threatening severe diseases including pneumonia and sepsis. Sa produces biofilms readily on biotic and abiotic surfaces. Biofilm cells are embedded in a protective polysaccharide matrix and show an innate resistance to antibiotics, disinfectants, and clearance by host defenses. Additionally, biofilms serve as a source for systemic dissemination. Moreover, infections associated with biofilms may result in longer hospitalizations, a need for surgery, and may even result in death. Agents that inhibit the formation of biofilms and virulence without affecting bacterial growth to avoid the development of drug resistance could be useful for therapeutic purposes. In this regard, we identified and purified a small cyclic peptide, gurmarin, from a plant source that inhibited the formation of Sa biofilm under in vitro growth conditions without affecting the viability of the bacterium. The purified peptide showed a predicted molecular size of ~4.2 kDa on SDS-PAGE. Transcriptomic analysis of Sa biofilm treated with peptide showed 161 differentially affected genes at a 2-fold change, and some of them include upregulation of genes involved in oxidoreductases and downregulation of genes involved in transferases and hydrolases. To determine the inhibitory effect of the peptide against Sa biofilm formation and virulence in vivo, we used a rat-implant biofilm model. Sa infected implants with or without peptide were placed under the neck skin of rats for seven days. Implants treated with peptide showed a reduction of CFU and lack of edema and sepsis when compared to that of control animals without peptide. Taken together, gurmarin peptide blocks Sa biofilm formation in vitro and in vivo and can be further developed for therapeutic use.
Insights
A plant-derived peptide, gurmarin, effectively inhibits Staphylococcus aureus (Sa) biofilm formation and virulence both in vitro and in vivo. This discovery offers a promising therapeutic strategy against dangerous bacterial infections without promoting drug resistance.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- Staphylococcus aureus (Sa) is an opportunistic pathogen causing diverse infections, from skin issues to sepsis.
- Sa biofilms are highly resistant to antibiotics and host defenses, leading to severe complications and increased mortality.
- Novel therapeutic agents inhibiting biofilm formation and virulence without impacting bacterial growth are needed to combat drug resistance.
Purpose of the Study:
- To identify and characterize a plant-derived agent capable of inhibiting Staphylococcus aureus biofilm formation and virulence.
- To evaluate the efficacy of the purified peptide in vitro and in vivo.
- To investigate the molecular mechanisms underlying the peptide's inhibitory effects.
Main Methods:
- Purification and characterization of gurmarin peptide from a plant source.
- In vitro assessment of gurmarin's effect on Staphylococcus aureus biofilm formation and bacterial viability.
- Transcriptomic analysis of peptide-treated Sa biofilms.
- In vivo evaluation using a rat-implant biofilm model to assess biofilm formation and associated symptoms.
Main Results:
- Gurmarin peptide purified from a plant source inhibited Staphylococcus aureus biofilm formation in vitro without affecting bacterial viability.
- Transcriptomic analysis revealed differential gene expression in peptide-treated biofilms, including altered oxidoreductase, transferase, and hydrolase activity.
- In vivo studies demonstrated that gurmarin peptide significantly reduced bacterial load (CFU) and prevented edema and sepsis in a rat-implant model.
Conclusions:
- Gurmarin peptide is a potent inhibitor of Staphylococcus aureus biofilm formation and virulence.
- The peptide demonstrates efficacy in both in vitro and in vivo models, suggesting therapeutic potential.
- Gurmarin represents a promising candidate for developing new anti-biofilm strategies against Staphylococcus aureus infections.
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