The Role and Therapeutic Potential of Host Defense Peptides — Introduction

The Role and Therapeutic Potential of Host Defense Peptides — Introduction

Hancock, R. E. W., & Sahl, H.-G. (2006). Cationic host defence peptides: novel antimicrobial strategies against old and new pathogens. Nature Reviews Drug Discovery, *5*(2), 123–130. https://doi.org/10.1038/nrd2201

The discovery of antibiotics in the 1930s marked one of the most revolutionary periods in medical history. The subsequent commercialization of penicillin, discovered by Alexander Fleming, along with other compounds, is estimated to have increased average human life expectancy by more than 10 years. This represents the largest single gain in life expectancy since the introduction of public health protocols in the late 19th century. However, in recent years, these impressive early gains have gradually diminished, partly due to increasing antibiotic resistance. Another sobering fact is that, aside from the introduction of linezolid in 2000, no new antibiotics have been brought to market since the 1960s. This discouraging trend has been further exacerbated by the abandonment of antibacterial drug discovery by many major pharmaceutical companies. 

Nevertheless, these companies, along with biotechnology firms, continue to develop antimicrobial treatments, including natural cationic host defense peptides—also known as cationic antimicrobial peptides. These peptides have been shown to possess both antimicrobial and immunomodulatory activities, both of which can be utilized for treating and preventing infectious diseases. In this article, we focus on the relationship between the structure and activity of these compounds and summarize recent advances in researching their potential clinical applications. 

Cationic antimicrobial peptides (CAMPs) is the classical term used to describe peptides with direct antimicrobial activity. They are typically less than 50 amino acids in length and carry a net charge ranging from +2 to >+10 due to the presence of lysine and arginine residues. These peptides often adopt amphipathic or amphiphilic structures. In most cases, cationic peptides must interact with biological membranes through their amphipathic nature to exert their activity, making this property crucial for their function. 

Current research on cationic peptides tends to focus on their potential as direct antimicrobial agents. While antimicrobial activity is an important characteristic of many studied peptides, especially natural ones, it is essential that the significant antibacterial effects observed under physiological conditions align with in vivo observations. Although it is often difficult to accurately measure concentrations at specific sites within the body—particularly in tissues—this distinction helps differentiate between the antimicrobial and immunomodulatory activities of these peptides. These activities are not mutually exclusive; a single peptide may, in principle, exhibit different functions in various tissue environments. However, recent studies have shown that these activities can be separated. 

Cationic peptides with both antimicrobial and immunomodulatory properties are widespread across nearly all species in the biological world. Although their activity depends on the host species and clinical context of infection, each function contributes diversely to host defense.