Antibiofilm Activities of Tritrpticin Analogs Against Pathogenic <i>Pseudomonas aeruginosa</i> PA01 Strains
In our previous work, we showed that short antimicrobial hexapeptides (AMPs) containing three Trp and three Arg residues had a potent antibiofilm activity against a pathogenic Gram-positive <i>Staphylococcus aureus</i> MRSA strain. However, the activity of these hexapeptides against a Gr...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/4/826 |
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| Summary: | In our previous work, we showed that short antimicrobial hexapeptides (AMPs) containing three Trp and three Arg residues had a potent antibiofilm activity against a pathogenic Gram-positive <i>Staphylococcus aureus</i> MRSA strain. However, the activity of these hexapeptides against a Gram-negative <i>Pseudomonas aeruginosa</i> PA01 strain was relatively poor. Herein, we tested the longer 13-residue synthetic AMP tritrpticin-NH<sub>2</sub> (Tritrp) and several of its analogs as potential antibiofilm agents that can prevent biofilm formation (MBIC) and/or cause biofilm dissolution (MBEC) for two <i>P. aeruginosa</i> PA01 strains, one of which expressed the GFP protein. Tritrp, a porcine cathelicidin, is currently the only known naturally occurring cationic AMP that has three Trp in sequence (WWW), a feature that was found to be important in our previous study. Our results show that several Tritrp analogs were effective. In particular, analogs with Pro substitutions that had altered peptide backbone structures compared to the naturally occurring amphipathic two-turn structure showed more potent MBIC and MBEC antibiofilm activities. Selectivity of the peptides towards <i>P. aeruginosa</i> could be improved by introducing the non-proteinogenic amino acid 2,3-diaminopropionic acid, rather than Arg or Lys, as the positively charged residues. Using <sup>1</sup>H NMR spectroscopy, we also reinvestigated the role of the two Pro residues in cis–trans isomerism of the peptide in aqueous solution. Overall, our results show that the WWW motif embedded in longer cationic AMPs has considerable potential to combat biofilm formation in pathogenic Gram-negative strains. |
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| ISSN: | 1420-3049 |