title: Antimicrobial Activity of Novel Synthetic Peptides Derived from Indolicidin and Ranalexin against Streptococcus pneumoniae.
abstract: 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.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Hassan Mahmood
authors.initials: HM
authors.lastname: Jindal
authors.affiliation: School of Pharmacy, Faculty of Science, University of Nottingham Malaysia Campus, Jalan Broga, 43500, Semenyih, Selangor, Malaysia.
authors.forename: Cheng Foh
authors.initials: CF
authors.lastname: Le
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Mohd Yasim
authors.initials: MY
authors.lastname: Mohd Yusof
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Rukumani Devi
authors.initials: RD
authors.lastname: Velayuthan
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Vannajan Sanghiran
authors.initials: VS
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Sharifuddin Md
authors.initials: SM
authors.lastname: Zain
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Diyana Mohd
authors.initials: DM
authors.lastname: Isa
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Shamala Devi
authors.initials: SD
authors.lastname: Sekaran
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D010456:Peptides, Cyclic; C073143:indolicidin; C086618:ranalexin