Antimicrobial Activity of Novel Synthetic Peptides Derived from Indolicidin and Ranalexin against Streptococcus pneumoniae

• Published in: PloS one 2015-06, Vol.10 (6), p.e0128532-e0128532
• Main Authors: Jindal, Hassan Mahmood, Le, Cheng Foh, Mohd Yusof, Mohd Yasim, Velayuthan, Rukumani Devi, Lee, Vannajan Sanghiran, Zain, Sharifuddin Md, Isa, Diyana Mohd, Sekaran, Shamala Devi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - pharmacology; Antibacterial activity; Antibiotics; Antimicrobial activity; Antimicrobial agents; Antimicrobial Cationic Peptides - chemistry; Antimicrobial peptides; Bacteria; Binding Sites; Ceftriaxone; Cell Line, Tumor; Cell Survival - drug effects; Chemical properties; Chemistry; Clinical isolates; Cytotoxicity; Design; Drug development; E coli; Erythrocytes; Erythromycin; Escherichia coli - drug effects; Hepatocytes; Humans; Indolicidin; Internet; Liver; Lungs; Medicine; Meningitis; Methicillin; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Minimum inhibitory concentration; Molecular chains; Molecular docking; Molecular Docking Simulation; Molecular Sequence Data; Multidrug resistance; Pathogens; Peptides; Peptides - chemistry; Peptides - pharmacology; Peptides, Cyclic - chemistry; Pneumolysin; Pneumonia; Protein A; Protein Structure, Tertiary; Proteins; PspA protein; Staphylococcus aureus; Staphylococcus aureus - drug effects; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Surface protein A; Synthetic peptides
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0128532

Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics in order to defeat multidrug-resistant bacteria such as Streptococcus pneumoniae. In this study, thirteen antimicrobial peptides were designed based on two natural peptides indolicidin and ranalexin. Our results revealed that four hybrid peptides RN7-IN10, RN7-IN9, RN7-IN8, and RN7-IN6 possess potent antibacterial activity against 30 pneumococcal clinical isolates (MIC 7.81-15.62µg/ml). These four hybrid peptides also showed broad spectrum antibacterial activity (7.81µg/ml) against S. aureus, methicillin resistant S. aureus (MRSA), and E. coli. Furthermore, the time killing assay results showed that the hybrid peptides were able to eliminate S. pneumoniae within less than one hour which is faster than the standard drugs erythromycin and ceftriaxone. The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line. The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values. The in silico molecular docking study was carried out to investigate the binding properties of peptides with three pneumococcal virulent targets by Autodock Vina. RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA) based on rigid docking studies. Our results suggest that the hybrid peptides could be suitable candidates for antibacterial drug development.