Antibacterial Activity of DesCys¹¹/Lys¹²/Lys¹³-(p-BthTX-I)₂K Sequence Conjugated to Cell-Penetrating Peptides

The resistance of microorganisms to antibiotics is occurring worldwide. An alternative against resistant bacteria has been antimicrobial peptides. Cell penetrating peptides are a family of peptides that are able to cross the biological membrane. In the present study, the peptide desCys¹¹/Lys¹²/Lys¹³(p-BthTX-I)₂K was coupled to the cell penetrating peptides PFVYLI, HIV-TAT (47-57) and AIP-6 to improve its antimicrobial action. The peptides were synthesized by SPPS. Circular dichroism spectroscopy was used to evaluated structure of conjugates. The biological activity was determined by broth microdilution tests and the minimum inhibitory concentration and the minimum bactericidal concentration were obtained. The hemolytic activity was performed to measure the toxicity against erythrocytes. The results obtained demonstrate that the peptides do not have a defined structure, which is consistent with the structure of desCys¹¹/Lys¹²/Lys¹³(p-BthTX-I)₂K. Conjugates showed activity against Gram-negative E. coli similar to the wild type peptide. However, the MIC decreased from 128 µM to values ​​between 16 µM and 8 µM in Gram-positive S. aureus. Except to PFVYLI conjugate, hemolytic activity was not found. These results showed that the addition of the fusion peptides to the original peptide, improves the activity of the peptide against Gram-positive bacteria, without decrease its activity in Gram-negative bacteria.