Table 5.
Antimicrobial (MIC) and hemolytic (MHC) activities of peptide analogs against Gram-positive bacteria, fungus and human red blood cells
| MHCa (µg/mL) | MICb (µg/mL) | Therapeutic indexe | MIC b (µg/mL) | Therapeutic indexf | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Peptides | hRBC |
S. aureus 622 (wt)c |
S. aureus 623 (methR)c |
S. epidermidis C621 (wt)c |
B. subtilis C971 (wt)c |
E. faecalis C625 (wt)c |
C. xerosis C875 (wt)c |
GMd | Foldd | MHC/MIC | Foldg | C. albicans | MHC/MIC | Foldg |
| V681 | 7.8 | 3.1 | 6.3 | 6.3 | 3.1 | 6.3 | 3.1 | 4.4 | 1.0 | 1.8 | 1.0 | 12.5 | 0.6 | 1.0 |
| d-V681 | 7.8 | 6.3 | 6.3 | 1.6 | 1.6 | 6.3 | 3.1 | 3.5 | 1.3 | 2.2 | 1.2 | 6.3 | 1.2 | 2.0 |
| V13AD | 31.3 | 1.6 | 3.1 | 1.6 | 3.1 | 12.5 | 1.6 | 2.8 | 1.6 | 11.2 | 6.2 | 12.5 | 2.5 | 4.2 |
| d-V13AL | 31.3 | 3.1 | 3.1 | 1.6 | 1.6 | 12.5 | 1.6 | 2.8 | 1.6 | 11.2 | 6.2 | 12.5 | 2.5 | 4.2 |
| V13KL | 250.0 | 12.5 | 12.5 | 6.3 | 3.1 | 50.0 | 1.6 | 7.9 | 0.6 | 31.6 | 17.6 | 50.0 | 5.0 | 8.3 |
| d-V13KD | 250.0h | 6.3 | 6.3 | 3.1 | 1.6 | 12.5 | 1.6 | 4.0 | 1.1 | 62.5 | 34.7 (69.4)h | 25.0 | 10.0 | 16.7 (33.4)h |
Hemolytic activity (maximal peptide concentration with no hemolysis after 18 h) was determined on human red blood cells (hRBC).
Antimicrobial and antifungal activities (minimal inhibitory concentration) are from three sets of determinations.
S. aureus, Staphylococcus aureus; S. epidermidis, Staphylococcus epidermidis; B. subtilis, Bacillus subtilis; E. faecalis, Enterococcus faecalis; C. xerosis, Corynebacterium xerosis; C. albicans, Candida albicans; wt, wild-type strain; methR, methicillin-resistant clinical strain.
GM denotes the geometric mean of MIC values from all six gram-positive microbial strains in this table. Fold denotes fold improvement in the geometric mean MIC compared with parent peptide V681.
Therapeutic index = MHC (µg/mL)/geometric mean MIC (µg/mL). Larger values indicate greater antimicrobial specificity.
Denotes the therapeutic index of the peptides against a fungus C. albicans.
Denotes fold improvement in the therapeutic index compared with parent peptide V681.
In the hemolysis time study, d-V13KD showed no hemolysis at 500 µg/mL for 8 h which would increase the fold improvement in the therapeutic index to 69.4- and 33.4-fold for gram-positive bacteria and C. albicans, respectively.