Antimicrobial peptides: key components of the innate immune system

Abstract

Life-threatening infectious diseases are on their way to cause a worldwide crisis, as treating them effectively is becoming increasingly difficult due to the emergence of antibiotic resistant strains. Antimicrobial peptides (AMPs) form an ancient type of innate immunity found universally in all living organisms, providing a principal first-line of defense against the invading pathogens. The unique diverse function and architecture of AMPs has attracted considerable attention by scientists, both in terms of understanding the basic biology of the innate immune system, and as a tool in the design of molecular templates for new anti-infective drugs. AMPs are gene-encoded short (<100 amino acids), amphipathic molecules with hydrophobic and cationic amino acids arranged spatially, which exhibit broad spectrum antimicrobial activity. AMPs have been the subject of natural evolution, as have the microbes, for hundreds of millions of years. Despite this long history of co-evolution, AMPs have not lost their ability to kill or inhibit the microbes totally, nor have the microbes learnt to avoid the lethal punch of AMPs. AMPs therefore have potential to provide an important breakthrough and form the basis for a new class of antibiotics. In this review, we would like to give an overview of cationic antimicrobial peptides, origin, structure, functions, and mode of action of AMPs, which are highly expressed and found in humans, as well as a brief discussion about widely abundant, well characterized AMPs in mammals, in addition to pharmaceutical aspects and the additional functions of AMPs.

(Lipo)polysaccharide interactions of antimicrobial peptides

“…Particularly relevant to the present discussion, sepsis remains the leading cause of death in intensive care units, with 30-40% overall mortality (≈70% for elderly and chronically ill patients) (2), and no efficient and safe drugs on the market. Considering this, as well as their attenuated susceptibility to resistance development, antimicrobial peptides (AMPs; also referred to as host defense peptides) have attracted considerable interest as potential therapeutics against both infections and resulting inflammation (3)(4)(5).…”

Activity of tick antimicrobial peptide from Ixodes persulcatus (persulcatusin) against cell membranes of drug-resistant Staphylococcus aureus

“…5 Antimicrobial peptides are integral components of the innate immune system of all living organisms, including mammals, plants and insects. 6 Antimicrobial peptides result in strong natural defense in arthropod, particularly antimicrobial peptides of silk moth 7,8 and beetle, 9 which belong to the defensin family. Persulcatusin (IP), a tick antimicrobial peptide found in the midgut of Ixodes persulcatus, exhibits antimicrobial activity against Gram-positive bacteria such as S. aureus.…”

Antimicrobial Peptides

“…AMPs are key components of the innate immune system, »10-40 amino-acids long, generally net positively charged, and containing a substantial fraction of hydrophobic residues. Although AMPs induce multiple damages in bacteria, including inhibition of DNA, RNA, and protein synthesis, their main mode of action is disruption of bacterial membranes (1)(2)(3). Several mechanisms for this have been suggested, including detergency-like packing disruption and formation of barrel-stave or toroidal pores ( Figure 1) (1)(2)(3)(4)(5).…”

“…Due to increasing antibiotic resistance, there is much current interest in novel therapeutic approaches, including antimicrobial peptides (AMPs) (1)(2)(3). AMPs are key components of the innate immune system, »10-40 amino-acids long, generally net positively charged, and containing a substantial fraction of hydrophobic residues.…”