This blog post examines the problem of superbugs caused by antibiotic resistance and the possibility that antimicrobial peptides can be an alternative.
Antibiotics are probably the first medicines that come to mind when we think of drugs used to kill germs. Antibiotics have played an essential role in the treatment of bacterial diseases and have become the most effective tool for preventing and treating infectious diseases. The first antibacterial drug we developed was penicillin, which is derived from blue mold, and it was a breakthrough in controlling bacterial diseases. The reason why antibiotics are still the most commonly used antibacterial agents is that they can suppress or eliminate bacteria in a short period of time due to their high efficacy. Nevertheless, the side effects of antibiotic use, especially the occurrence of resistant bacteria, have emerged as a major problem. As a result, scientists have been continuously striving to explore new antibacterial substances with less resistance.
In addition to antibiotics, there are various antibacterial substances found in our bodies and in nature, such as lysozyme and antibacterial peptides. For example, lysozyme is contained in our tears and saliva and plays a role in inhibiting bacterial invasion. In addition, there are antibacterial substances secreted by living organisms in nature to protect themselves from external bacteria. However, antibiotics are still widely used because they have an excellent ability to eliminate bacteria and can be used widely regardless of the type of bacteria. However, as bacteria are becoming resistant to antibiotics and turning into “superbacteria,” the number of patients infected with such bacteria is also increasing. Against this backdrop, interest in other antibacterial substances, especially naturally derived antibacterial substances, is growing as alternatives to antibiotics.
The antibacterial peptide that will be the focus of this article is, as the name suggests, a peptide that has the ability to kill germs. Peptides are a general term for compounds in which amino acids, the basic elements that make up proteins, are linked by peptide bonds, and usually refer to compounds with 100 or fewer amino acids. Antimicrobial peptides were first discovered in the secretion of frogs’ epidermis in 1962, and since then, they have been actively studied in various organisms, including insects, fish, and plants. These substances are attracting attention as a promising alternative to address the problem of drug-resistant bacteria thanks to their unique mechanism of action, which directly destroys the cell membrane of bacteria.
Antibiotics chemically neutralize germs by inhibiting the components of cell membranes or protein synthesis. However, if bacteria mutate and change the way they synthesize the components of cell membranes, antibiotics will no longer be effective. This is the cause of the rapid increase in antibiotic-resistant germs, and the number of resistant germ infections that are difficult to treat in hospital settings is increasing. On the other hand, antimicrobial peptides eliminate bacteria by directly acting on the cell membrane of prokaryotic organisms and physically destroying them.
Antibacterial peptides are unique in that they have both hydrophobic and hydrophilic parts, making them effective in targeting bacterial cell membranes. The hydrophilic positively charged part strongly binds to the negatively charged cell membrane of prokaryotic cells, and the hydrophobic part interacts with the hydrophobic part of the cell membrane to form a hole in the cell membrane. This action changes the permeability of the cell membrane, which eventually destroys the cell. In the case of eukaryotic cells, the net charge on the surface of the cell membrane is close to zero, so the interaction with the antimicrobial peptide is weak, and cholesterol reduces the fluidity of the phospholipids, making it difficult for the antimicrobial peptide to insert itself into the cell membrane. As a result, antimicrobial peptides are relatively safe to use because they show high activity in destroying prokaryotic cells while minimizing the destruction of human cells.
Antimicrobial peptides have the advantage of quickly killing germs and reducing the chance of developing resistant germs, but their ability to kill germs is somewhat limited compared to some antibiotics. In addition, there is a limit to how easily it can be broken down by proteolytic enzymes in the affected area when applied to the human body. To overcome this limitation, research is needed to chemically modify antibacterial peptides obtained from nature or to discover new antibacterial peptides with resistance to resistance.
In fact, HG1, an antibacterial peptide derived from sea pineapple, is attracting 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, it has been developed into a drug that alleviates skin diseases such as atopy and acne. Currently, the utility of antimicrobial peptides is being actively studied in various fields, including skin diseases, anti-aging functions, and the development of livestock with increased disease resistance. These studies are opening up the possibility that antimicrobial peptides can be used in various fields, including medicine, agriculture, and environmental protection, as new antibiotics in the future.
