Intracellular Targeting Mechanisms by Antimicrobial Peptides.
Antimicrobial peptides (AMPs) are expressed in various living organisms as first-line host defenses against potential harmful encounters in their surroundings. AMPs are short polycationic peptides exhibiting various antimicrobial activities. The principal antibacterial activity is attributed to the membrane-lytic mechanism which directly interferes with the integrity of the bacterial cell membrane and cell wall. In addition, a number of AMPs form a transmembrane channel in the membrane by self-aggregation or polymerization, leading to cytoplasm leakage and cell death. However, an increasing body of evidence has demonstrated that AMPs are able to exert intracellular inhibitory activities as the primary or supportive mechanisms to achieve efficient killing. In this review, we focus on the major intracellular targeting activities reported in AMPs, which include nucleic acids and protein biosynthesis and protein-folding, protease, cell division, cell wall biosynthesis, and lipopolysaccharide inhibition. These multifunctional AMPs could serve as the potential lead peptides for the future development of novel antibacterial agents with improved therapeutic profiles.
School of Pharmacy, Faculty of Science, The University of Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia chengfoh.le@nottingham.edu.my.|School of Biosciences, Faculty of Science, The University of Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia.
Cheng-Foh
CF
Le
School of Pharmacy, Faculty of Science, The University of Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia.
Chee-Mun
CM
Fang
Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Shamala Devi
SD
Sekaran
D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D014176:Protein Biosynthesis / Q000187:drug effects*; D017510:Protein Folding / Q000187:drug effects
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides
antibiotic resistance; antimicrobial peptides; intracellular targeting; membrane lysis; novel antibiotics