title: In vitro properties of designed antimicrobial peptides that exhibit potent antipneumococcal activity and produces synergism in combination with penicillin.
abstract: Antimicrobial peptides (AMPs) represent a promising class of novel antimicrobial agents owing to their potent antimicrobial activity. In this study, two lead peptides from unrelated classes of AMPs were systematically hybridized into a series of five hybrid peptides (DM1-DM5) with conserved N- and C-termini. This approach allows sequence bridging of two highly dissimilar AMPs and enables sequence-activity relationship be detailed down to single amino acid level. Presence of specific amino acids and physicochemical properties were used to describe the antipneumococcal activity of these hybrids. Results obtained suggested that cell wall and/or membrane targeting could be the principal mechanism exerted by the hybrids leading to microbial cell killing. Moreover, the pneumocidal rate was greater than penicillin (PEN). Combination treatment with both DMs and PEN produced synergism. The hybrids were also broad spectrum against multiple common clinical bacteria. Sequence analysis showed that presence of specific residues has a major role in affecting the antimicrobial and cell toxicity of the hybrids than physicochemical properties. Future studies should continue to investigate the mechanisms of actions, in vivo therapeutic potential, and improve rational peptide design based on the current strategy.
authors.affiliation: 1] Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia [2] School of Pharmacy, Faculty of Science, University of Nottingham Malaysia Campus, 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, Kuala Lumpur, Malaysia.
authors.forename: Mohd Yasim Mohd
authors.initials: MY
authors.lastname: Yusof
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hamimah
authors.initials: H
authors.lastname: Hassan
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