In this blog post, we’ll explore the problem of superbugs caused by antibiotic resistance and the potential for antimicrobial peptides to serve as an alternative.
When thinking of medications used to kill bacteria, antibiotics are likely the first thing that comes to mind. Antibiotics have played an essential role in treating bacterial diseases and have established themselves as the most effective tools for preventing and treating infectious diseases. The very first antimicrobial drug we developed was penicillin, derived from Penicillium mold, which marked a groundbreaking breakthrough in controlling bacterial diseases. The reason antibiotics remain the most commonly used antimicrobial agents today is their high efficacy, which allows them to suppress or eliminate bacteria in a short period of time. Nevertheless, the side effects caused by antibiotic use, particularly the emergence of drug-resistant bacteria, have become a major concern. Consequently, scientists have been continuously striving to discover new antimicrobial substances with lower resistance rates.
In addition to antibiotics, there are various antimicrobial substances found in the human body or in nature, such as lysozyme and antimicrobial peptides. For example, lysozyme is present in our tears and saliva and plays a role in inhibiting bacterial invasion. Furthermore, there are antimicrobial substances secreted by organisms in nature to protect themselves from external bacteria. However, antibiotics are still widely used because of their exceptional ability to eliminate bacteria and their broad applicability regardless of the bacterial species. Yet, as cases of bacteria developing resistance to antibiotics and transforming into “superbugs” have gradually increased, the number of patients infected by them has also risen. Against this backdrop, interest in other antimicrobial substances—particularly those derived from nature—is growing as alternatives to antibiotics.
The antimicrobial peptides that will be the focus of this article are, as the name suggests, peptides with the ability to kill bacteria. Peptides are a general term for compounds formed by amino acids—the basic building blocks of proteins—linked by peptide bonds, typically referring to chains of 100 or fewer amino acids. Antimicrobial peptides were first discovered in 1962 in the secretions of frog skin and have since been obtained from various organisms, including insects, fish, and plants, and are currently the subject of active research. Thanks to their unique mechanism of action—which directly destroys the bacterial cell membrane—these substances are attracting attention as a promising alternative for addressing the problem of antibiotic-resistant bacteria.
Antibiotics chemically neutralize bacteria by inhibiting the synthesis of cell membrane components or proteins. However, if bacteria mutate and alter the synthesis of cell membrane components, antibiotics become ineffective. This is the cause of the rapid increase in antibiotic-resistant bacteria, and cases of difficult-to-treat resistant bacterial infections are on the rise in hospital settings. In contrast, antimicrobial peptides eliminate bacteria by acting directly on the cell membranes of prokaryotes and physically disrupting them.
Antimicrobial peptides are unique in that they possess both hydrophobic and hydrophilic regions, making them effective at targeting bacterial cell membranes. The hydrophilic, positively charged regions bind strongly to the negatively charged cell membranes of prokaryotic cells, while the hydrophobic regions interact with the hydrophobic parts of the cell membrane to form pores. This action alters the permeability of the cell membrane, ultimately destroying the cell. In eukaryotic cells, the net charge on the cell membrane surface is close to zero, resulting in weak interaction with antimicrobial peptides. Additionally, cholesterol reduces the fluidity of phospholipids, preventing antimicrobial peptides from easily inserting into the cell membrane. Consequently, antimicrobial peptides exhibit high activity against prokaryotic cells while minimizing damage to human cells, making them relatively safe for use.
While antimicrobial peptides have the advantage of rapidly killing bacteria and reducing the likelihood of resistance development, their bactericidal activity is somewhat lower than that of some antibiotics. Additionally, when applied to the human body, they are easily degraded by proteolytic enzymes present at the site of application. To overcome these limitations, research is needed to chemically modify naturally derived antimicrobial peptides or to identify new antimicrobial peptides that are resistant to resistance.
In fact, HG1, an antimicrobial peptide derived from the sea squirt, is gaining attention as an example that has partially overcome these limitations. HG1 has been shown to be effective in treating skin diseases and, based on this, has been developed into a medication to alleviate skin conditions such as atopic dermatitis and acne. Currently, the utility of antimicrobial peptides is being actively researched in various fields, including not only skin diseases but also anti-aging functions and the development of livestock with enhanced disease resistance. These studies open up the possibility that antimicrobial peptides could be usefully applied as new antimicrobial agents in various fields such as pharmaceuticals, agriculture, and environmental protection.
