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Updated: Feb 1, 2026
Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
The novel cationic cell-penetrating peptide PEP-NJSM is highly active against Staphylococcus epidermidis biofilm
Sami Mnif1, Marwa Jardak1, Imen Graiet2
1Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, University of Sfax, Road Sidi Mansour km 6, PO BOX 1177, 3018 Sfax, Tunisia.
Abstract:
A cationic cell-penetrating peptide PEP-NJSM was identified in human virus proteomes by a screening of charge clusters in protein sequences generating Cell-Penetrating Peptides (CPP). PEP-NJSM was selectively active against Gram-positive Staphylococcus epidermidis as antibacterial agent with MIC value of 128 μM compared to the Gram-negative Pseudomonas aeruginosa strain with MIC value exceeded 512 μM. The selected peptide exhibited an important anti-biofilm activity even at sub-MIC levels. PEP-NJSM could prevent biofilm formation and increase the mortality of cells inside mature S. epidermidis biofilm. The results demonstrated that PEP-NJSM presented an important anti-adherent activity. It showed a S. epidermidis inhibition of biofilm formation >84% at a concentration of 256 μM (2 X MIC) and remained active even at a concentration of 4 μM with 32% of inhibition. The eradication of the established biofilm was observed at a concentration of 256 μM with 55.7% of biofilm eradication. The peptide was active against mature biofilm even at low concentration of 0.5 μM with approximately 22.9% of eradication. PEP-NJSM exhibited low hemolytic activity and cytotoxicity against mammalian cells. Our results demonstrate that PEP-NJSM could have a potential role in the treatment of diseases related to Staphylococcus epidermidis infection.
Insights
A novel cationic cell-penetrating peptide, PEP-NJSM, shows potent antibacterial and anti-biofilm activity against Staphylococcus epidermidis. This peptide offers potential for treating infections caused by this common pathogen.
Area of Science:
- Microbiology
- Biochemistry
- Drug Discovery
Background:
- Staphylococcus epidermidis is a leading cause of device-related infections.
- Developing novel antimicrobial agents is crucial to combat antibiotic resistance.
- Cell-penetrating peptides (CPPs) are emerging as potential therapeutic candidates.
Purpose of the Study:
- To identify and characterize a novel cationic cell-penetrating peptide (PEP-NJSM) with antimicrobial properties.
- To evaluate the antibacterial and anti-biofilm efficacy of PEP-NJSM against Staphylococcus epidermidis.
- To assess the safety profile of PEP-NJSM regarding hemolytic and cytotoxic effects.
Main Methods:
- Screening of human virus proteomes for cationic charge clusters to identify potential CPPs.
- Determination of Minimum Inhibitory Concentration (MIC) against Gram-positive (S. epidermidis) and Gram-negative (P. aeruginosa) bacteria.
- Assessment of anti-adherent, biofilm inhibition, and biofilm eradication activities of PEP-NJSM.
- Evaluation of hemolytic activity and cytotoxicity against mammalian cells.
Main Results:
- PEP-NJSM demonstrated selective activity against S. epidermidis (MIC 128 μM) compared to P. aeruginosa (MIC >512 μM).
- Significant inhibition of S. epidermidis biofilm formation (>84% at 256 μM) and eradication of established biofilms (55.7% at 256 μM) were observed.
- PEP-NJSM exhibited anti-biofilm activity even at sub-MIC levels and low concentrations (e.g., 32% inhibition at 4 μM, 22.9% eradication at 0.5 μM).
- The peptide showed low hemolytic activity and cytotoxicity against mammalian cells.
Conclusions:
- PEP-NJSM is a promising cationic cell-penetrating peptide with potent antibacterial and anti-biofilm activities against Staphylococcus epidermidis.
- Its ability to inhibit biofilm formation and eradicate established biofilms, coupled with a favorable safety profile, suggests therapeutic potential.
- PEP-NJSM could serve as a novel agent for treating S. epidermidis-related infections, particularly those involving biofilms.
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