Abstract: Antimicrobial peptides in insects are important components of the host immune defense system, with small molecular mass, good thermal stability, and wide antibacterial spectrum. Because antimicrobial peptides have their own unique chemical structure, their mechanism of action is different from antibiotics and chemical drugs, which can effectively inhibit fungi, viruses and parasites, while pathogens do not produce resistance, and can selectively kill tumor cells, but there are no toxic side effects for humans and animals. Therefore, antimicrobial peptides have good development prospects in biological agriculture and medicine.
Insect food rich in antimicrobial peptides
1. Comparison of insect antimicrobial peptides and antibiotics
The discovery of antibiotics is a milestone in the history of medicine. The discovery of antibiotics has made a revolutionary leap in the treatment of pathogenic infectious diseases and has become a powerful weapon for people to fight pathogenic infections. However, with the large use of antibiotics, the continuous increase of drug-resistant strains and multi-drug-resistant strains in recent years has also greatly improved the resistance of pathogenic bacteria, and anti-infection treatment has fallen into the crisis of drug-resistant bacteria. Taking penicillin as an example, the amount of penicillin used is now tens of times greater than when it was first discovered. More seriously, the antibiotic-resistant flora that is now emerging is resistant, and almost all antibiotics have no effect on them. Moreover, in recent decades, no new antibiotics have been able to solve the problem of their resistance. In response to drug-resistant bacteria infections, humans are constantly researching and developing new antimicrobial drugs. The antimicrobial peptides that have emerged in recent years are a new class of antibacterial drugs with great potential for development.
Antimicrobial peptides are a class of peptide bioactive substances produced by the biological immune system that resist the infection of external pathogens, and are widely present in insects, plants, animals and humans. Insects are the most abundant and abundant inferior animals on Earth, and the houseflies in particular have the highest reproductive rate. Like other higher animals, insects also have a complete cellular and humoral immune response system, which has various functions of defending against pathogen infection, maintaining self-stability and immune supervision, but its immune system is far less specialized, perfect and developed than that of higher animals. Insects have neither specialized and efficient immune organs and tissues (T, B lymphatic systems), nor the presence of immunoglobulins and complement in body fluids, and insects can occupy a great advantage in nature, indicating that their defense system must have its own uniqueness. The study of insect immunity is currently a rapidly developing new collar
Take the housefly as an example, for thousands of years, flies have been haunted in dirty places, a fly usually carries more than 60 kinds of germs, but also carries a lot of viruses and parasite eggs, its body carries more germs, more than 800 times outside the body, flies can spread typhoid fever, dysentery, cholera and other more than 30 kinds of diseases. However, the fly itself is not infected, not invaded, the antibacterial peptide extracted from the fly maggot, is a special antibacterial, antiviral active substance, after scientists have explored and found that the fly has a special insect immune component, that is, antibacterial active protein or called antibacterial peptide, according to the measurement, this antibacterial peptide only needs one ten-thousandth of the concentration to kill a variety of germs.
Antimicrobial peptides in nature
2. The mechanism of action of antimicrobial peptides and antibiotics has found that antimicrobial peptides have no adverse effects on normal mammalian cells and insect cells in vitro culture for 48~72 h, but have selective killing effects on tumor cells. This selective lethal effect may be related to differences in cytoskeleton structure. Antimicrobial peptides have a killing effect on human myeloid leukemia cells (K552), Ascitesoma, rectal cancer (HR8340) and liver cancer cells (BEL-7402). Experiments have shown that the amazing efficacy of maggots in treating traumatic infections is through the secretion of antibacterial active substances. However, with the discovery of antibiotics and their good antibacterial effects, maggot treatment has gradually become forgotten. In recent years, due to the emergence of a large number of resistant strains and the adverse reactions caused by chemical antibacterial drugs, clinicians and researchers have refocused their attention and begun to study the anti-infection treatment of fly maggots. Because of the patient's difficulty in the treatment of live fly maggots, it is particularly important to extract the antibacterial peptides secreted by fly maggots, identify their molecular structure, or produce highly efficient antibacterial peptides through artificial synthesis and molecular cloning for anti-infective therapy.
In addition to non-specific antibacterial, fungal, viral and other pathogens, antimicrobial peptides also have the effect of anti-tumor cells, so they are also called peptide antibiotics. Due to its broad-spectrum antibacterial properties, it has a killing effect on multi-drug-resistant bacteria and tumor cells, and does not destroy the normal cells of the body. It is expected to become a good drug for anti-tumor and anti-infection, so that humans and animals can get rid of the "drug-resistant bacteria crisis" and find a new way to treat tumors, and will bring revolutionary progress to the field of clinical medicine and clinical pharmacology, with broad development and application prospects, and is a hot spot in the current development and research of anti-pathogenic microbial drugs.
At present, people have successfully cloned the cDNA of some antimicrobial peptides and attached them to baculovirus or other vectors for expression in eukaryotic systems such as insects and yeasts and in the prokaryotic system of E. coli. By using the broad-spectrum antibacterial characteristics of antimicrobial peptides, the cloned antimicrobial peptide genes are introduced into animals and plants, and the transgenic animals and plants obtained have obvious disease resistance, which shows that the research on insect antimicrobial peptides not only has important theoretical significance, but also has broad application prospects. When insects are stimulated by external antigens, such as the invasion of pathogenic microorganisms, they are rapidly induced to synthesize antimicrobial peptides. Antimicrobial peptides also have the characteristics of thermal stability, good water solubility, no immunogenicity, and a wide antibacterial spectrum. Antimicrobial peptides are now considered to be a class of defensive polypeptides that are prevalent in the body of bacteria to insects and even higher mammals, called the "second defense system".
Antimicrobial peptides differ from conventional antibiotics, which are the products synthesized by a series of enzymes, while antimicrobial peptides are the products of a specific code. In the sterilization mechanism, antibiotics are generally by inhibiting the synthesis of bacterial cell walls, proteins or DNA to achieve the purpose of sterilization, so the antibacterial of antibiotics is generally with special receptors, bacteria are easy to produce resistance to antibiotics through mutation, and antimicrobial peptides are generally not special antibodies when antibacterial, antimicrobial peptides are generally through the physical action of causing perforation of cell membranes and achieve broad-spectrum antibacterial effects, so the use of antimicrobial peptides is not easy to produce antibacterial and cross-resistance.
These antibacterial substances induced by insects not only have a broad spectrum of antibacterial and antiviral viability, but also have antifungal, antimalarial and anti-trypanosomiasis activities, insect antibacterial peptides have a specific killing effect on tumor cells and cancer cells, and are harmless to normal cells, and what is more interesting is that some insect antibacterial substances have obvious inhibitory effects on some DNA and RNA viruses. At present, a lot of progress has been made in the induction mechanism of antibacterial proteins and antibacterial peptides, the primary and tertiary structures of antibacterial proteins and antibacterial peptides, and the mechanism of action of antibacterial substances on pathogens such as bacteria and fungi.
3. Classification of antibacterial peptides
According to their structure and function, antimicrobial peptides are divided into: bactericidal peptides, defensins, magainin - proline-containing antibacterial peptides (Praline-rich peptides), bee toxins (Melittin) - glycine-rich antimicrobial peptides (Glysine-rich peptides). Insect antimicrobial peptides include cecropins, insect defensins, proline-rich antimicrobial peptides ( Proline-richpeptides ) and glycine-rich antimicrobial peptides (Glysine-rich pep-tides).
Antimicrobial peptides can generally be divided into the following categories according to their sources: (1) Mammalian antimicrobial peptides, mammalian antimicrobial peptides are mainly present in neutrophils and epithelial cells of the skin and mucous membranes, of which the most studied are defensin antibacterial peptides, which are also the largest class in the antimicrobial peptide family; (2) Amphibian antibacterial peptides, amphibian skin is exposed for a long time, in the long-term natural selection process to resist the invasion of harmful environmental factors gradually formed a series of protective mechanisms - their skin secretions contain a large number of bactericidal and defense against natural enemies of biological amines and antimicrobial peptides, the content of which is unmatched by mammals, so it is called a large reservoir of biological amines and antibacterial peptides; (3) Insect antimicrobial peptides, insects in the animal kingdom the largest number, the most widely distributed, and has a high degree of adaptability and defense mechanism, insect immune defense system without antibodies, complement participation, mainly by a series of antimicrobial peptides play a role, since 1981 Boma et al. first induced antibacterial peptides from the pupa of the Xigubi silkworm - silkworm, more than 170 kinds of insect antimicrobial peptides have been found; (4) Plant antimicrobial peptides, like insects, although plants have no specific immune system, have a certain killing effect on animal cells, and compared with animal and bacterial antibacterial peptides, the activity of plant defenses against fungi is very high; (5) Bacterial antibacterial peptides, although antibacterial peptides can be inhibited, but bacteria can also produce antibacterial peptides to protect themselves, of which, bacteriocin is the most common class of antibacterial peptides, it can specifically kill competing bacteria, and harmless to the host itself.
4. Application prospects of insect antibacterial peptides
In the long process of natural evolution, various animals have established a balanced microbial flora symbiotic ecosystem in their bodies, and established a set of mechanisms to maintain the homeostasis of their in vivo flora. Antimicrobial peptides are one of the main factors in this mechanism and are widely present in all vertebrate and invertebrate bodies. The intestinal microbial flora of higher animals is developed, and the intestinal endogenous antibacterial peptides of different animals can inhibit their corresponding exogenous pathogenic bacteria, while there is no killing effect on microorganisms and animal cells in the co-existing ecosystem of animal intestines, that is, the intestinal antibacterial peptides of higher animals have "species" specificity. Although the higher animal intestinal antimicrobial peptides have this advantage, their expression and secretion in animals is limited, coupled with the increasing intensification of modern livestock and poultry breeding industry, pathogen transmission and invasion and various stress effects are increasingly strengthened, making it more difficult for livestock and poultry to express limited antibacterial peptides in the animals themselves to play a great role in the health care of animals. If antimicrobial peptides can be used as feed additives, the health and growth of raised animals can be specifically maintained when they are invaded or stressed by exogenous pathogens. The search for endogenous antibacterial substances of various reared animals, with modern biotechnological methods, the industrial production of these series of products with animal "species" specificity or specificity in anti-pathogenic bacteria, will undoubtedly be
A way out of the "post-antibiotic era".
Piglet diarrhea, dairy mastitis and various viral diseases such as swine fever and chicken newcastle disease have always been tricky diseases, which seriously affect the development of animal husbandry and breeding. Drawing on the successful insect antimicrobial peptide transgenic project, such as transgenic mosquitoes, transgenic potatoes, transgenic rice, etc., the specific antimicrobial peptide gene is transferred to the specific cells of livestock and poultry to be expressed, so as to produce new varieties of disease resistance, which is a new idea for the development of animal husbandry production, and the prospect is far-reaching. Antimicrobial peptide gene expression regulation and antimicrobial peptide additive studies have shown that the use of antibiotic additives seriously disrupts the microbial balance of the animal intestine, and is easy to remain in the animal body, which seriously affects the quality of livestock products and human health, and the application of environmentally friendly antimicrobial peptide additives will undoubtedly be a new way out. The test of antimicrobial peptides in livestock industry of houseflies showed that the tests on broilers showed that antimicrobial peptides could improve the feed conversion rate of broilers by 3.64% and the survival rate by 10%. The test of suckling pig shows that the antimicrobial peptide of domestic fly can effectively reduce the incidence of yellow diarrhea and white diarrhea in piglets, and significantly improve the survival rate of piglets.
Flies, black water flies, this amazing species created by nature, will bring us a ray of light against nature. As a newly discovered substance, the application direction of antimicrobial peptides is still under continuous exploration. After many studies, antimicrobial peptides have shown attractive application prospects—— — that is, antibiotic alternative drugs.