Chris Gothard
CPC Scientific, Sunnyvale, USA

Abstract

Coevolution among microorganisms and higher organisms has resulted in the adaptation of mammalian cellular and systemic host defense strategies to defend against microbial pathogens. Host defense peptides (HDPs) are nature’s defense against harmful pathogens, but have not precluded the need for antibiotic drugs. Bacteria adapt quickly to conventional antibiotics because the targets of these compounds are very specific and can be avoided by simple genetic mutations. HDPs, or antimicrobial peptides (AMPs), remain important drug candidates because the peptides target relatively non-specific regions in bacteria (e.g., membranes) and have a broad range of functions that includes membrane disruption, apoptosis, and immunomodulation. This article serves as general review of the pore-forming mechanisms of various AMPs. In addition, the article sheds light on the multifunctional approach taken by many AMPs to evade the defensive strategies adopted by microbes.

INTRODUCTION

Antimicrobial Peptides (AMPs) are found in virtually every living organism—bacteria, fungi, plants, invertebrates, and vertebrates—and play a critical role in the innate and acquired immune responses to pathogenic attacks. AMPs are released by various cells and organelles, such as immune cells (granulocytes and macrophages), epithelial cells (vaginal epithelium, respiratory epithelium, and oral cavity epithelium), and the small intestine. The antimicrobial effects of peptides were first observed in 1966 by Zeya and Spitznagel (1, 4). During their studies of lysosomal cationic proteins and peptides, they noticed many of the peptides contained basic amino acids like arginine and lysine. Soon after, they experimentally demonstrated that ‘lysosomal cationic proteins (LCPs) had antibacterial activity against certain gram-positive and gram-negative bacteria.
One of the primary motivations for the development of peptide antibiotics is the emergence of multi-drug-resistant bacteria from the overuse of antibiotics. According to European Centre for Disease Prevention and Control Antimicrobial Resistance Interactive Database (EARS- ...