Abstract
Increasing resistance of pathogenic bacteria to antibiotics is a serious problem in health care system and has intensified the search for potent novel drugs. Cationic antibacterial peptides are the most abundant antibiotics in nature and have been frequently proposed as new anti-infective agents. In this study, a set of diastereomeric peptides is researched about their antibiotic activity against multiple drug resistant clinical isolates and their modes of action against gram-positive cocci. MIC was suggested by the NCCLS against ten clinically isolated antibiotic-resistant strains. Mode of action studies included killing kinetics and a series of experiments designed to characterize the impact of the diastereomeric peptides on bacterial membranes. The tested diastereomers displayed high antimicrobial and broad spectrum activity with D-P5-18mer. The antimicrobial activity of diastereomeric-P5-18mer was two times stronger against gram-negative bacteria than either CA-MA-20mer or P5-18mer. When tested against ten clinically isolated antibiotic-resistant strains in the presence of 0, 150, or 300 mM NaCl, diastereomeric-P5-18mer retained strong activity against all bacteria, yet showed little or no cytotoxicity against the HaCaT human keratinocyte cell line. Finally, D-P5-18mer showed resistance against trypsin digestion unlike other analogues.
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