Table 4.
Antimicrobial (MIC) and hemolytic (MHC) activities of peptide analogs against Gram-negative bacteria and human red blood cells
| MHCa (µg/mL) | MICb (µg/mL) | Therapeutic indexf | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Peptides | hRBC |
E. coli C498 (wt)c |
E. coli C500 (abs)c |
St C587 (wt)c |
St C610 (abs)c |
Pa H187 (wt)c |
Pa H188 (abs)c |
GMd | Folde | MHC/MIC | Foldg |
| V681 | 7.8 | 6.3 | 3.1 | 12.5 | 3.1 | 6.3 | 3.1 | 5.0 | 1.0 | 1.6 | 1.0 |
| d-V681 | 7.8 | 6.3 | 3.1 | 12.5 | 6.3 | 6.3 | 6.3 | 6.3 | 0.8 | 1.2 | 0.8 |
| V13AD | 31.3 | 3.1 | 1.6 | 12.5 | 3.1 | 3.1 | 1.6 | 3.1 | 1.6 | 10.1 | 6.3 |
| d-V13AL | 31.3 | 3.1 | 3.1 | 12.5 | 3.1 | 3.1 | 3.1 | 3.9 | 1.3 | 8.0 | 5.0 |
| V13KL | 250.0 | 3.1 | 3.1 | 6.3 | 3.1 | 6.3 | 3.1 | 3.9 | 1.3 | 64.1 | 40.1 |
| d-V13Kc | 250.0h | 3.1 | 3.1 | 6.3 | 3.1 | 6.3 | 3.1 | 3.9 | 1.3 | 64.1 | 40.1 (80.2)h |
Hemolytic activity (maximal peptide concentration with no hemolysis after 18 h) was determined on human red blood cells (hRBC).
Antimicrobial activity (minimal inhibitory concentration) is from three sets of determinations.
E. coli, Escherichia coli; St, Salmonella typhimurium; Pa, Pseudomonas aeruginosa; wt, wild-type laboratory strain; abs, antibiotic-sensitive strain.
GM denotes the geometric mean of MIC values from all six microbial strains in this table.
Denotes fold improvement in the geometric mean of MIC compared with parent peptide V681.
Therapeutic index = MHC (µg/mL)/geometric mean of MIC (µg/mL). Larger values indicate greater antimicrobial specificity.
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 80.2-fold.