LL-37-derived membrane-active FK-13 analogs possessing cell selectivity, anti-biofilm activity and synergy with chloramphenicol and anti-inflammatory activity.
Rajasekaran. Ganesan G; Kim. Eun Young EY; Shin. Song Yub SY
Key Findings
- FK-13-a1 and FK-13-a7 are 6.3‑ and 2.3‑times more selective for bacterial cells over human cells than the original LL-37.
- Both analogs are more potent against drug‑resistant bacteria (MRSA, MDRPA, VREF) and work synergistically with chloramphenicol.
- They retain anti‑inflammatory activity, remain effective in salty conditions and human serum, and disrupt bacterial membranes quickly.
Practical Outcomes
- For biohackers interested in antimicrobial peptides, these findings suggest that short, engineered LL-37 fragments could be a more viable option for topical or experimental use, especially against resistant infections. However, they are not yet approved or widely available, so any self‑experimentation would require custom synthesis and careful safety testing.
Summary
Scientists made two shorter versions of the human peptide LL-37 (called FK-13-a1 and FK-13-a7) that kill bacteria better, are less harmful to human cells, work well with the antibiotic chloramphenicol, and still calm inflammation. These new peptides could be cheaper and more effective than the original LL-37, but they are still in early research stages.
Abstract
Although the human-derived antimicrobial peptide (AMP) LL-37 has potent antimicrobial and anti-inflammatory activities, its therapeutic application is limited by its low cell selectivity and high production cost due to its large size. To overcome these problems, we tried to develop novel LL-37-derived short α-helical AMPs with improved cell selectivity and without a significant loss of anti-inflammatory activity relative to that of parental LL-37. Using amino acid substitution, we designed and synthesized a series of FK13 analogs based on the sequence of the 13-meric short FK13 peptide (residues 17-29 of LL-37) that has been identified as the region responsible for the antimicrobial activity of LL-37. Among the designed FK13 analogs, FK-13-a1 and FK-13-a7 showed high cell selectivity and retained the anti-inflammatory activity. The therapeutic index (a measure of cell selectivity) of FK-13-a1 and FK-13-a7 was 6.3- and 2.3-fold that of parental LL-37, respectively. Furthermore, FK-13-a1 and FK-13-a7 displayed more potent antimicrobial activity against antibiotic-resistant bacteria including MRSA, MDRPA, and VREF, than did LL-37. In addition, FK-13-a1 and FK-13-a7 exhibited greater synergistic effects with chloramphenicol against MRSA and MDRPA and were more effective anti-biofilm agents against MDRPA than LL-37 was. Moreover, FK-13-a1 and FK-13-a7 maintained their activities in the presence of physiological salts and human serum. SYTOX green uptake, membrane depolarization and killing kinetics revealed that FK13-a1 and FK13-a7 kills microbial cells by permeabilizing the cell membrane and damaging membrane integrity. Taken together, our results suggest that FK13-a1 and FK13-a7 can be developed as novel antimicrobial/anti-inflammatory agents.
Study Information
pubmed
2017
2017-02-01T00:00:00.000Z
10.1016/j.bbamem.2017.01.037
86
64