title: In vivo efficacy and molecular docking of designed peptide that exhibits potent antipneumococcal activity and synergises in combination with penicillin.
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.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Cheng-Foh
authors.initials: CF
authors.lastname: Le
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mohd Yasim Mohd
authors.initials: MY
authors.lastname: Yusof
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mahmood Ameen Abdulla
authors.initials: MA
authors.lastname: Hassan
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Vannajan Sanghiran
authors.initials: VS
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 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, Kuala Lumpur, Malaysia.
authors.forename: Shamala Devi
authors.initials: SD
authors.lastname: Sekaran
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D004195:Disease Models, Animal; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000737:chemistry / Q000378:metabolism; D010400:Penicillin G / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D011485:Protein Binding; D011487:Protein Conformation; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000378:metabolism; D013301:Streptolysins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D010455:Peptides; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; C051592:pneumococcal surface protein A; D009238:N-Acetylmuramoyl-L-alanine Amidase; D010400:Penicillin G