By increasing the positive charge of a natural tree shrew antimicrobial peptide, researchers created TC-LAR-18, which is up to 128 times more potent against bacteria while remaining safe and resistance-resistant.
Up to 128-fold strongerThe engineered TC-LAR-18 peptide showed 4 to 128 times better antimicrobial activity than the original tree shrew peptide, while remaining non-toxic to normal cells.
What the researchers found
Researchers engineered a novel antimicrobial peptide called TC-LAR-18 from a tree shrew cathelicidin by increasing its net positive charge from +4 to +8. The modified peptide showed 4- to 128-fold stronger antibacterial activity than the original TC-33, effectively killed both free-floating and biofilm-associated bacteria, and caused no hemolysis or cytotoxicity at concentrations up to 100 μg/mL.
Critically, TC-LAR-18 demonstrated rapid membrane-disrupting action with a low tendency to induce bacterial resistance, and provided significant protection against skin bacterial infections in a mouse model.
Why it matters
Antibiotic resistance is one of the most urgent global health threats. Antimicrobial peptides represent an alternative approach because bacteria have difficulty developing resistance to them. This study shows that rational design — specifically increasing positive charge — can dramatically improve a natural peptide's killing power while maintaining safety, potentially yielding new weapons against multidrug-resistant infections.
How the study worked
The researchers took a natural cathelicidin antimicrobial peptide (TC-33) from the Chinese tree shrew and redesigned it through peptide truncation and glutamic acid substitutions to increase its net positive charge. They then tested TC-LAR-18's antibacterial activity against multiple bacterial species (planktonic and biofilm), assessed safety via hemolysis and cytotoxicity assays, evaluated resistance induction potential, and tested therapeutic efficacy in a mouse skin infection model.
Who was studied
In vitro bacterial cultures and mice with skin bacterial infections
What this study cannot tell us
The study only tested TC-LAR-18 in a skin infection mouse model; efficacy against systemic infections is unknown. Long-term safety and pharmacokinetic profiles were not assessed. The peptide's stability in biological fluids and potential for large-scale production were not addressed in this study.
How to read the evidence
This is a preclinical study combining in vitro antibacterial testing with an in vivo mouse skin infection model. It demonstrates strong proof-of-concept but has not been tested in humans.
When this study was published
Published in 2024, this is a recent study in the active field of antimicrobial peptide engineering.
The bigger picture
With antibiotic resistance rising worldwide, researchers are looking to antimicrobial peptides as alternatives that bacteria struggle to resist. This study demonstrates that rational peptide engineering — adjusting charge properties — can transform a weak natural peptide into a potent drug candidate, offering a template for developing new antimicrobials from animal-derived peptides.
Questions still open
- Could TC-LAR-18 be effective against systemic infections, not just skin infections?
- How does TC-LAR-18's stability and half-life compare to conventional antibiotics in clinical settings?
- Can this charge-optimization approach be applied to other natural antimicrobial peptides to create a library of candidates?
Common questions
Why is increasing a peptide's positive charge important for killing bacteria?
Could bacteria develop resistance to this new peptide?
Read the original research
Novel Tree Shrew-Derived Antimicrobial Peptide with Broad-Spectrum Antibacterial Activity.
ACS omega, 9(45), 45279-45288
Citation
Luo, Lin; Cai, Ying; Su, Yunhan; Li, Chenxi; Tian, Gengzhou; Wang, Xingyu; Wu, Zhongxiang; Chen, Wenlin; Zhang, Tianyu; Zhang, Zhiye. (2024). Novel Tree Shrew-Derived Antimicrobial Peptide with Broad-Spectrum Antibacterial Activity.. ACS omega, 9(45), 45279-45288. https://doi.org/10.1021/acsomega.4c06857