In vivo efficacy and molecular docking of designed peptide that exhibits potent antipneumococcal activity and synergises in combination with penicillin

Cheng-Foh Le; Mohd Yasim Mohd Yusof; Mahmood Ameen Abdulla Hassan; Vannajan Sanghiran Lee; Diyana Mohd Isa; Shamala Devi Sekaran

doi:10.1038/srep11886

In vivo efficacy and molecular docking of designed peptide that exhibits potent antipneumococcal activity and synergises in combination with penicillin

Sci Rep. 2015 Jul 9:5:11886. doi: 10.1038/srep11886.

Authors

Cheng-Foh Le¹, Mohd Yasim Mohd Yusof¹, Mahmood Ameen Abdulla Hassan², Vannajan Sanghiran Lee³, Diyana Mohd Isa³, Shamala Devi Sekaran¹

Affiliations

¹ Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
² Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
³ Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.

Abstract

We have previously designed a series of antimicrobial peptides (AMPs) and in the current study, the in vivo therapeutic efficacy and toxicity were investigated. Among all the peptides, DM3 conferred protection to a substantial proportion of the lethally infected mice caused by a strain of penicillin-resistant Streptococcus pneumoniae. Synergism was reported and therapeutic efficacy was significantly enhanced when DM3 was formulated in combination with penicillin (PEN). No toxicity was observed in mice receiving these treatments. The in silico molecular docking study results showed that, DM3 has a strong affinity towards three protein targets; autolysin and pneumococcal surface protein A (pspA). Thus AMPs could serve as supporting therapeutics in combination with conventional antibiotics to enhance treatment outcome.

Publication types

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

MeSH terms

Animals
Anti-Bacterial Agents / administration & dosage
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antimicrobial Cationic Peptides / administration & dosage
Antimicrobial Cationic Peptides / chemistry
Antimicrobial Cationic Peptides / pharmacology
Bacterial Proteins / chemistry
Bacterial Proteins / metabolism
Binding Sites
Disease Models, Animal
Drug Synergism
Humans
Mice
Models, Molecular
Molecular Docking Simulation
N-Acetylmuramoyl-L-alanine Amidase / chemistry
N-Acetylmuramoyl-L-alanine Amidase / metabolism
Penicillin G / pharmacology*
Peptides / chemistry
Peptides / pharmacology*
Pneumococcal Infections / drug therapy
Pneumococcal Infections / microbiology*
Pneumococcal Infections / mortality
Pneumococcal Infections / pathology
Protein Binding
Protein Conformation
Streptococcus pneumoniae / drug effects*
Streptococcus pneumoniae / metabolism
Streptolysins / chemistry
Streptolysins / metabolism

Substances

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Bacterial Proteins
Peptides
Streptolysins
plY protein, Streptococcus pneumoniae
pneumococcal surface protein A
N-Acetylmuramoyl-L-alanine Amidase
Penicillin G