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

Hassan Mahmood Jindal; Cheng Foh Le; Mohd Yasim Mohd Yusof; Rukumani Devi Velayuthan; Vannajan Sanghiran Lee; Sharifuddin Md Zain; Diyana Mohd Isa; Shamala Devi Sekaran

doi:10.1371/journal.pone.0128532

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

PLoS One. 2015 Jun 5;10(6):e0128532. doi: 10.1371/journal.pone.0128532. eCollection 2015.

Authors

Hassan Mahmood Jindal¹, Cheng Foh Le², Mohd Yasim Mohd Yusof¹, Rukumani Devi Velayuthan¹, Vannajan Sanghiran Lee³, Sharifuddin Md Zain³, Diyana Mohd Isa³, Shamala Devi Sekaran¹

Affiliations

¹ Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
² School of Pharmacy, Faculty of Science, University of Nottingham Malaysia Campus, Jalan Broga, 43500, Semenyih, Selangor, Malaysia.
³ Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Anti-Infective Agents / chemical synthesis*
Anti-Infective Agents / pharmacology
Antimicrobial Cationic Peptides / chemistry*
Binding Sites
Cell Line, Tumor
Cell Survival / drug effects
Escherichia coli / drug effects
Humans
Methicillin-Resistant Staphylococcus aureus / drug effects
Microbial Sensitivity Tests
Molecular Docking Simulation
Molecular Sequence Data
Peptides / chemistry*
Peptides / pharmacology
Peptides, Cyclic / chemistry*
Protein Structure, Tertiary
Staphylococcus aureus / drug effects
Streptococcus pneumoniae / drug effects

Substances

Anti-Infective Agents
Antimicrobial Cationic Peptides
Peptides
Peptides, Cyclic
indolicidin
ranalexin

Grants and funding

This study was supported by University of Malaya High Impact Research grant (reference number: UM.C/HIR/MOHE/MED/40, account number: H-848 20001-E000079) and University of Malaya Research Grant (UMRG Project no. RP020C-14AFR and RP001C-13ICT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.