Antibiotics are the mainstay of germ-killing drugs, but they are becoming less and less effective due to the problem of resistant bacteria. Recently, antimicrobial peptides found in a variety of organisms have emerged as a new class of antimicrobials, which eliminate bacteria by physically disrupting cell membranes. Antimicrobial peptides destroy bacteria by forming holes in cell membranes and are less likely to develop resistance, making them a promising alternative to tackling superbugs. However, in human applications, they must overcome the limitation of being degraded by proteolytic enzymes.
When it comes to medicines used to kill bacteria, the first thing that comes to mind is antibiotics. Antibiotics have played an essential role in treating bacterial diseases and have become the most efficient tool for preventing and treating infectious diseases. One of the first antibacterials we developed was penicillin, which was derived from a blue mold and was a major breakthrough in controlling bacterial diseases. Antibiotics are still the most commonly used antimicrobials today because of their high potency and ability to inhibit or eliminate bacteria in a short period of time. Nevertheless, the side effects of antibiotic use have become a major concern, especially the development of resistant bacteria. As a result, scientists have been searching for new antimicrobials that are less resistant.
In addition to antibiotics, there are a variety of other antimicrobials found in our bodies and in nature, such as lysozymes and antimicrobial peptides. Lysozyme, for example, is found in our tears and saliva, where it acts as a barrier to bacterial invasion, and there are other antimicrobial substances in nature that organisms secrete to protect themselves from foreign germs. However, antibiotics are still widely used because of their ability to kill germs and their broad spectrum of use, regardless of the type of bacteria. However, as more and more bacteria become resistant to antibiotics and turn into “superbugs,” the number of patients who become infected with them is increasing. Against this backdrop, there has been a growing interest in other antimicrobial substances as alternatives to antibiotics, especially naturally occurring antimicrobials.
Antimicrobial peptides, as the name suggests, are peptides that have the ability to kill bacteria. A peptide is a general term for a compound made up of amino acids, the building blocks of proteins, linked together by peptide bonds, usually no more than 100 amino acids. Antimicrobial peptides were first discovered in 1962 in the epidermal secretions of frogs, and have since been discovered and studied in a wide variety of organisms, including insects, fish, and plants. Their unique mechanism of action, which directly disrupts the cell membrane of bacteria, has made them a promising alternative to the problem of resistant bacteria.
Antibiotics chemically neutralize bacteria by interfering with cell membrane components or protein synthesis. However, when bacteria mutate to change the way they synthesize cell membrane components, antibiotics are no longer effective. This contributes to the rapid rise of antibiotic-resistant bacteria, and hospital settings are seeing an increase in the number of resistant infections that are difficult to treat. Antimicrobial peptides, on the other hand, eliminate bacteria by acting directly on the cell membranes of prokaryotic organisms and physically disrupting them.
Antimicrobial peptides uniquely have both hydrophobic and hydrophilic parts, which makes them effective at targeting bacterial cell membranes. The hydrophilic, positively charged portion binds strongly to the negatively charged membrane of the prokaryotic cell, while the hydrophobic portion interacts with the hydrophobic portion of the cell membrane to form a hole in the membrane. This action changes the permeability of the cell membrane and eventually destroys the cell. In eukaryotes, the alpha charge on the surface of the cell membrane is close to zero, so the interaction with antimicrobial peptides is weak, and cholesterol reduces the fluidity of phospholipids, making it difficult for antimicrobial peptides to insert into the cell membrane. As a result, antimicrobial peptides are relatively safe to use because they are highly active in destroying prokaryotic cells with minimal cellular destruction in humans.
While antimicrobial peptides have the advantage of killing bacteria quickly and reducing the chance of resistant bacteria developing, their ability to kill bacteria is limited by their somewhat lower activity compared to some antibiotics. In addition, when applied to the human body, they are easily degraded by proteolytic enzymes in the affected area. To overcome these limitations, research is needed to chemically modify naturally occurring antimicrobial peptides or to find new antimicrobial peptides that are resistant to resistance.
In fact, HG1, an antimicrobial peptide obtained from the silken mud crab, has been recognized as an example of overcoming some of these limitations. HG1 has been shown to be effective in treating skin diseases and has been developed as a drug to alleviate skin diseases such as atopy and acne. Currently, the utility of antimicrobial peptides is being actively studied not only in skin diseases, but also in various fields such as anti-aging functions and the development of disease-resistant livestock. These studies open up the possibility that antimicrobial peptides, as new antibiotics, could be useful in many fields, including medicine, agriculture, and environmental protection.
