Antimicrobial Peptides: Mechanism of Action

*Tanu Singh, Princy Choudhary and Sangeeta Singh*

## **Abstract**

Antimicrobial peptides (AMPs) are a diverse class of small peptides that are found in most life forms ranging from microorganisms to humans. They can provoke innate immunity response and show activity against a wide range of microbial cells which includes bacteria, fungi, viruses, parasites, and even cancer cells. In recent years AMPs have gained considerable attention as a therapeutic agent since bacterial resistance towards conventional antibiotics is accelerating rapidly. Thus, it is essential to analyze the mechanism of action (MOA) of AMPs to enhance their use as therapeutics. The MOA of AMPs is classified into two broad categories: direct killing and immunological regulation. The direct killing action mechanism is categorized into membrane targeting and non-membrane targeting mechanisms. There are several models and biophysical techniques which determine the action mechanism of antimicrobial peptides.

**Keywords:** Antimicrobial peptides, mechanism of action, microbes, membrane disruption, antibiotics

### **1. Introduction**

Antimicrobial peptides (AMPs) are a broad class of small peptide molecules that are found in most life forms ranging from microorganisms to humans. They can provoke an innate immune response in various species, thus they represent the first line of defense against foreign microbes [1]. They show antimicrobial activity against a wide range of microbial cells including bacteria, viruses, fungus, parasites, and even cancer cells. Although, Gram-negative bacteria and Gram-positive bacteria are the most studied targets of AMPs [2]. In recent years AMPs have gained significant attention as potential therapeutic agents since bacterial resistance towards conventional antibiotics is accelerating rapidly [3].

Antimicrobial peptides (AMPs) are considered as attractive alternative antimicrobial agents, as these small biological molecules have mechanism-of-action (MOA) different from the conventional antibiotics, thus they can be applied to combat against various microorganisms even drug-resistant ones [4]. Several properties of these peptides like net charge, hydrophobicity, secondary structure, etc. lead them to have therapeutic action. AMPs are positively charged amphipathic molecules that kill bacteria by using two major MOAs. In the first MOA, AMPs cause membrane disruption, leading to cell lysis and finally cell death. In the second mechanism, AMPs traverse through the cell membrane without disrupting it and inhibit critical intracellular functions by binding to DNA, RNA, or intracellular proteins [5–7]. There are several models which have been used to explain the

membrane binding activity of AMPs. Based on the ability to form pores the models are divided into two groups: pore-forming models and non-pore forming models [6]. A large number of biophysical techniques are available that describe their action mechanism whether these peptides disrupt microbial membrane or they target intracellular activities [7].
