Related Experiment Video
Updated: Aug 24, 2026
Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
Therapeutic Potential of Antimicrobial Peptide PN5 against Multidrug-Resistant E. coli and Anti-Inflammatory Activity
Da Dam Kang1, Jonggwan Park2, Yoonkyung Park1,3
1Department of Biomedical Science, Chosun Universitygrid.254187.d, Gwangju, South Korea.
Abstract:
Antibiotic-resistant bacteria have become a public health problem. Thus, antimicrobial peptides (AMPs) have been evaluated as substitutes for antibiotics. Herein, we investigated PN5 derived from Pinus densiflora (pine needle). PN5 exhibited antimicrobial activity without causing cytotoxic effects. Based on these results, we examined the mode of action of PN5 against Gram-negative and -positive bacteria. PN5 exhibited membrane permeabilization ability, had antimicrobial stability in the presence of elastase, a proteolytic enzyme, and did not induce resistance in bacteria. Bacterial lipopolysaccharide (LPS) induces an inflammatory response in RAW 264.7 macrophages. PN5 suppressed proinflammatory cytokines mediated by NF-κB and mitogen-activated protein kinase signaling. In C57BL/6J mice treated with LPS and d-galactosamine, PN5 exhibited anti-inflammatory activity in inflamed mouse livers. Our results indicate that PN5 has antimicrobial and anti-inflammatory activities and thus may be useful as an antimicrobial agent to treat septic shock caused by multidrug-resistant (MDR) Escherichia coli without causing further resistance. IMPORTANCE Antibiotic-resistant bacteria are a global health concern. There is no effective treatment for antibiotic-resistant bacteria, and new alternatives are being suggested. The present study found antibacterial and anti-inflammatory activities of PN5 derived from Pinus densiflora (pine needle), and further investigated the therapeutic effect in a mouse septic model. As a mechanism of antibacterial activity, PN5 exhibited the membrane permeabilization ability of the toroidal model, and treated strains did not develop drug resistance during serial passages. PN5 showed immunomodulatory properties of neutralizing LPS in a mouse septic model. These results indicate that PN5 could be a new and promising therapeutic agent for bacterial infectious disease caused by antibiotic-resistant strains.
Insights
A novel antimicrobial peptide, PN5 from pine needles, shows potent antibacterial and anti-inflammatory effects against drug-resistant bacteria. It effectively treats septic shock in mice without inducing further resistance, offering a promising alternative to conventional antibiotics.
Area of Science:
- Biochemistry
- Microbiology
- Immunology
Background:
- Antibiotic-resistant bacteria pose a significant global health threat.
- Antimicrobial peptides (AMPs) are being explored as alternatives to conventional antibiotics.
- There is a critical need for novel therapeutic agents to combat multidrug-resistant infections.
Purpose of the Study:
- To investigate the antimicrobial and anti-inflammatory properties of PN5, a peptide derived from Pinus densiflora (pine needle).
- To elucidate the mechanism of action of PN5 against Gram-negative and Gram-positive bacteria.
- To evaluate the therapeutic potential of PN5 in a mouse model of septic shock.
Main Methods:
- PN5 was isolated and its antimicrobial activity was assessed against various bacterial strains.
- Cytotoxicity assays were performed to determine the safety profile of PN5.
- Mechanisms of action, including membrane permeabilization and resistance induction, were investigated.
- Anti-inflammatory effects were evaluated in vitro using macrophages and in vivo using a mouse septic shock model.
Main Results:
- PN5 demonstrated significant antimicrobial activity against multidrug-resistant bacteria without exhibiting cytotoxic effects.
- PN5 acts by permeabilizing bacterial membranes and does not induce bacterial resistance.
- PN5 suppressed pro-inflammatory cytokine production and demonstrated therapeutic efficacy in a mouse model of LPS-induced septic shock.
- PN5 showed stability against proteolytic degradation by elastase.
Conclusions:
- PN5 possesses potent antimicrobial and anti-inflammatory activities.
- PN5 is a promising candidate for the development of new therapeutic agents against infections caused by antibiotic-resistant bacteria.
- PN5 may serve as a valuable treatment for conditions like septic shock, offering a novel approach to combatting antimicrobial resistance.
