Lysozyme

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Lysozyme C ( Gallus gallus )
Lysozyme C (Gallus gallus)
Structure of lysozyme according to PDB  132L

Existing structural data: see UniProt

Mass / length primary structure 14.3 kDa / 129 amino acids
Secondary to quaternary structure (β) αα (β) βββαα, lysozyme-like
Identifier
Gene name (s) LYZ
External IDs
Drug information
ATC code D06 BB07 J05 AX02
Enzyme classification
EC, category 3.2.1.17 ,  glycosidase
Response type Hydrolysis of β-1,4-glycosidic bonds between NAM and NAG
Substrate Peptidoglycan
Products Fission products
Occurrence
Homology family Lactalbumin / lysozyme
Parent taxon Slime molds , sponges , bilateria , fungi, bacteria, phages
Orthologue
human House mouse
Entrez 4069 17105
Ensemble ENSG00000090382 ENSMUSG00000069516
UniProt P61626 P08905
Refseq (mRNA) NM_000239 NM_017372
Refseq (protein) NP_000230 NP_059068
Gene locus Chr 12: 69.35 - 69.35 Mb Chr 10: 117.28 - 117.28 Mb
PubMed search 4069 17105

Lysozyme (also muramidase ) is an enzyme , the β-1,4- glycosidic linkages between N-acetylmuramic acid - (NAM) and N-acetylglucosamine (NAG) in peptidoglycans , composed of sugar derivatives and peptides macromolecules hydrolyzed . Lysozymes occur as part of the innate immune system in animals and can also be found in plants, fungi, bacteria and bacteriophages . In humans cause mutations in LYZ - gene to a rare hereditary form of amyloidosis .

history

There are several thousand scientific publications on lysozymes. Some of the first publications and those that are important beyond the research area of ​​lysozymes are briefly discussed here.

Protein crystal of a lysozyme.

The antibacterial property of chicken egg whites, which can be traced back to lysozyme, was first described by Lashchenko in 1909. The term “lysozyme” was only introduced in 1922 by Alexander Fleming (1881–1955), who gave the enzyme its name. He observed the antibacterial effect of lysozyme in the nasal mucus on the bacterium Micrococcus lysodeikticus and was also able to determine this effect on other human secretions and tissues .

The egg white lysozyme was the first fully sequenced enzyme to contain all of the canonical amino acid residues . The three-dimensional structure of lysozyme from chicken egg white (HEWL) determined by X-ray structure analysis was first described in 1965 by David Chilton Phillips (1924-1999). It was the second structure of a protein, as well as the first of an enzyme, that could be determined by X-ray scattering. Lysozyme was also the first enzyme based on the structure of which a detailed and specific catalytic mechanism for the enzyme was proposed. This work provided an explanation of how the structure of enzymes increases the speed of a chemical reaction. The mechanism proposed by Phillips has long been supported by experimental evidence and was not revised until 2001 based on new findings.

Classification

The assignment of the lysozymes to the different types is based on their amino acid sequence and their biochemical and enzymatic properties. In the Henrissat classification, lysozymes belong to the glycosidase families 22 to 25 and lytic transglycosidases belong to the glycosidase families 23, 102, 103 and 104.

In addition to lysozymes and lytic transglycosidases, there are other peptidoglycan-degrading enzymes such as N-acetyl-β- D -glucosaminidases, N-acetylmuramyl- L -alanine amidases and various endopeptidases.

In animals, three main types of lysozymes that differ from one another have been identified, which are usually referred to as c-type ( chicken or conventional-type ), g-type ( goose-type ) and i-type ( invertebrate-type ). There are also lysozymes that cannot be assigned to any of the aforementioned types, such as those from Dictyostelium discoideum ( UniProt Q8T1G4 ) or the sponge Suberites domuncula ( UniProt Q50JA0 ). Viral lysozymes are divided into v-type, λ-type, g-type and CH-type. Some viral enzymes are still called lysozymes for historical reasons, even though they are not β-1,4-N-acetylmuramidases. The lysozymes discovered in plants all have chitinase activity, but not all chitinases can hydrolyze peptidoglycans. They are divided into h-type and g-type chitinases / lysozymes. The lysozyme activity of many plant chitinases has not yet been investigated and some cannot be assigned due to a lack of sequence information. Lysozymes in bacteria are functionally differentiated into β-1,4-N-acetylmuramidases and β-1,4-N, 6-O-diacetylmuramidases.

Occurrence

Lysozymes in animals

c-type lysozymes

Humans ( UniProt P61626 , PDB  1LZS ), mammals , birds (e.g. chicken : UniProt P00698 , PDB  1LZC ), reptiles , amphibians and fish produce lysozymes of the c-type or at least have corresponding genes in their genome . So far, however, hardly any information is available on reptiles and amphibians. Among the invertebrates that were completely sequenced up to 2009 , genes coding for c-type lysozyme could only be identified in one lancet fish ( Branchiostoma belcheri tsingtauense ) and in arthropods . In butterflies , Diptera , termites and Schnabelkerfen from the class of insects as well as spiders and crustaceans c-type lysozymes were found and complete in all previously sequenced insect genomes was at least one gene are found, the homologous to c-type lysozyme is. A subgroup are the calcium-ion-binding lysozymes, to which for example the lysozyme from mare's milk ( UniProt P11376 , PDB  2EQL ) belongs. This subgroup is of particular interest in the discussion about the evolutionary formation of α-lactalbumin . A search for c-type lyszyme-like genes in the human genome reveals nine genes, one of which codes for lysozyme C and one for α-lactalbumin. Four others are predominantly expressed in the testes and appear to play a role in reproduction. This could be shown in mice for two of these genes. The other four genes have not yet been characterized. Several c-type lyszyme-like genes can also be found in other mammals. Possible orthologous genes for the different human genes could be found in most of the mammalian genomes.

g-type lysozymes

Lysozymes of the g-type owe their name to the first discovery in the egg white of the Emden goose . Since then it has been characterized for several bird species such as the chicken, black swan , African ostrich , rhea and cassowary . (Structure of a g-type lysozyme of a gray goose : UniProt P00718 , PDB  154L ). In chicken birds , the c-type lysozyme dominates in the egg white. In goose birds , depending on the species, c-type, g-type or both types of lysozyme may be present in the albumen. It was not until 2001 that it was shown that g-type lysozymes occur outside the class of birds. A database search found homologous proteins in humans, mammals, fish (e.g. cod : UniProt B9TU22 , PDB  3gxr ) and amphibians. Functional proteins have also been found in invertebrates such as scallops , oysters and some tunicates . There are no g-type lysozymes in the genomes of Anopheles gambiae , Apis mellifera , Drosophila melanogaster , Drosophila pseudoobscura , Caenorhabditis briggsae and Caenorhabditis elegans . One of the two human proteins homologous to g-type lysozyme is expressed in the kidney. The other is expressed in the lacrimal gland and to a lesser extent in the testes and is active.

i-type lysozymes

So far, i-type lysozyme were in the tribes mollusks (eg with a. Clam : UniProt Q8IU26 , PDB  2DQA ), annelids , echinoderms , nematodes are found and arthropods. They are absent from all available vertebrate genomes.

Viral lysozymes

v-type lysozymes

By 1996, 13 bacteriophages with v-type lysozymes had been described. Seven of the bacteriophages infected gram-negative bacteria and the other six gram-positive bacteria. In the T4 phage three lysozymes are for example encoding of which the product of the gene e, the examined best phage lysozyme is ( UniProt P00720 , PDB  148L ). The approximately 18 k Da lysozyme destroys the cell wall of Escherichia coli at the end of the infection cycle after the inner membrane has been modified by another phage protein. The lysozyme hydrolyzes the glycosidic bond behind N-acetylmuramic acid residues, which are modified with a peptide side chain. The N-acetamido group is also required for the activity of the lysozyme. A structure of T4 lysozyme with substrate was published by R. Kuroki. An overview of the studies with T4 lysozyme is given in the review by WA Baase et al. a. given. The numerous studies on T4 lysozyme provide insights into the folding and stability of proteins in general and T4 lysozyme in particular.

λ-type lysozymes

The λ-type lysozymes are named after the lysozyme of the λ phage ( UniProt P03706 , PDB  3D3D ). The lysozyme of the λ phage is not a hydrolase , but a lytic transglycosidase .

g-type lysozymes

Viral g-type lysozymes, such as that of Enterobacteria phage PRD1 ( UniProt P13559 ), are in part similar in their sequence to animal g-type lysozymes.

Lysozymes in plants

h-type chitinases / lysozymes

The name of this type goes back to two enzymes called Hevamine ( UniProt P23472 , PDB  1HVQ ), which occur in special vacuoles of the rubber tree Hevea brasiliensis and in natural rubber and were isolated as early as 1976. Lysozyme activity in 1983 and chitinase activity in 1990 were detected for these enzymes. Homologous chitinases have now been found in z. B. in field cress Arabidopsis thaliana , cucumber , tobacco , as well as in the yeast fungus Saccharomyces cerevisiae and other fungi detected in the genome. However, no lysozyme activity could be determined for the chitinase from the cucumber. The h-type chitinases are differentiated into class III and class V chitinases based on the sequence. In the Henrissat classification, h-type chitinases belong to the glycosidase family 18 (GH18), which is widespread in archaea , prokaryotes and eukaryotes.

b-type chitinases / lysozymes

In terms of their amino acid sequence, these chitinases have no similarities to h-type chitinases. They can be divided into three classes based on their amino acid sequence (I, II and IV). The name goes back to a class I chitinase from barley (English barley ) back ( UniProt P23951 , PDB  2BAA ). Lysozyme activity has been demonstrated for these and some other class I chitinases. However, the specific lysozyme activity is significantly lower than that of active h-type chitinases or HEWL. In other class I and class II chitinases, the specific lysozyme activity was about four orders of magnitude lower than in HEWL or could not be determined. No data has yet been published on the lysozyme activity of class IV chitinases. The "lysozyme" from papaya ( PDB  3CQL ) has a specific lysozyme activity of 35% compared to HEWL. In the classification by Henrissat b-type chitinases belong to the family of glycosidases 19 (GH19), in addition to plants only Actinobacteria , green non-sulfur bacteria , purple bacteria is some arthropods and nematodes to find.

Further chitinases / lysozymes from plants

For the lysozyme of the amate fig tree Ficus glabrata (specific lysozyme activity 85% compared to HEWL) there is a detailed description of the enzymatic properties, but an assignment is not yet possible due to the missing amino acid sequence.

CH-type lysozymes

The lysozyme of the fungus Chalaropsis sp. ( UniProt P00721 ) is a β-1,4-N, 6-O-diacetylmuramidase, which can also hydrolyze O-acetylated peptidoglycan. Related lysozymes were in some Streptomyces TYPES ( UniProt P25310 , PDB  1JFX ), in Lactobacillus acidophilus and Clostridium acetobutylicum ( UniProt P34020 z) and a plurality of bacteriophage (eg. Lactobacillus phage MV1 : UniProt P33486 and Streptococcus phage Cp-1 : UniProt P15057 ) found.

Biological importance

Function of lysozymes in animals and humans

In mammals and humans, lysozyme occurs in many secretions such as tear fluid , saliva , the secretions of the respiratory tract , in blood serum , in the cerebrospinal fluid , in the amniotic fluid , in the cervical mucus and in the milk . It is produced in the tissues of the respiratory tract , in the kidneys and in the intestinal mucosa as well as by neutrophils and macrophages . Under physiological conditions, about 80% of the lysozyme in blood plasma is due to the breakdown of neutrophils. Monocytes and macrophages can actively secrete lysozyme . Lysozyme is part of the innate immune system and serves to defend against bacteria. The peptidoglycan cell wall of gram-positive bacteria can be attacked directly by lysozyme. In gram-negative bacteria, the outer membrane can be made permeable by other components of the innate immune system, such as lactoferrin , defensins and cathelicidins , so that these can also be attacked by lysozyme. In addition to the direct antibacterial effect, the release of peptidoglycan fragments leads to a modulation of the immune system via peptidoglycan-recognizing receptors. So far, no experimental studies are available on the function of g-type lysozymes in mammals. Lysozymes in birds are mostly found in eggs. The expression of various lysozymes in intestinal epithelial cells has been demonstrated for chickens, so that a protective effect against pathogenic bacteria in the intestine can be assumed. A direct proof of this function is not yet available. In fish, lysozyme activity has been demonstrated in the head kidney, the key organ of the fish immune system, the spleen , the gills , in the blood, the skin, the digestive tract and in fish eggs. For several c- and g-type lysozymes an antibacterial effect against gram-positive and gram-negative bacteria could be shown. Above all, the high expression of g-type lysozymes in the skin, the gills and the intestinal epithelium suggest a defense function. Lysozyme could be isolated from the albumen of reptile eggs. Beyond that, however, no information is available on occurrence and function. Insects have effective inducible immune defenses. When exposed to bacteria, they produce a number of antibacterial peptides and proteins in the hemolymph , including lysozymes.

Some animals use lysozymes as digestive enzymes to use bacteria as a source of food. Some of these types of lysozyme show an increased resistance to proteases and an optimum pH in the acidic range.

The structure and properties of the lysozyme produced in the cow's stomach was described by Nonaka et al. a. examined.

Function of the lysozymes in plants

Since so far all plant lysozymes also have a chitinase activity, this has a broader pH optimum and the lysozyme activity is in some cases significantly lower or completely absent, these proteins are possibly intended for defense against fungi.

Function of lysozymes in bacteriophages

A variety of methods have been developed for infecting bacteria from bacteriophages. In some cases, lysozymes are also involved, which enable infection through a locally limited breakdown of the peptidoglycan. With a large excess of phage particles, "external lysis" could also be observed in these cases. Two strategies are known for the release of phage particles at the end of an infection cycle. One without lysozymes, in which a porin forms holes in the membrane through which the phage particles can escape. This is the case, for example, with E. coli phages MS2 and фX174 . In the second strategy for larger phage, such as T4 - , T7 - or λ phage is used, in addition to the Porin still Lysozyme and / or amidases are produced which hydrolyze either the polysaccharides or cross-linking the peptides in the peptidoglycan. The endolysins can be present in dissolved form in the cytoplasm, as in the case of T4 or λ phages . There are also phages, such as the Enterobacteria phage P1 , in which the endolysin ( UniProt Q37875 ) is transported into the periplasm via the host's Sec system and is present in an inactivated form ( PDB 1XJU ) bound to the membrane. Depolarization of the membrane by a holin leads to activation of the endolysin ( PDB 1XJT ) and cell lysis .   

Function of lysozymes in bacteria

For the growth and division of bacterial cells, not only are enzymes required that build up the peptidoglycan, but also those that can break it down again locally. These must be easily controllable and their activity regulated. Because of their potential danger to bacterial cells, they are known as autolysins . This includes some bacterial lysozymes, such as Streptomyces lysozyme. Work on the lytic transglycosylase "Slt35" ( UniProt P41052 , PDB  1d0k ) from E. coli and the N-acetylglucosaminidases from Enterococcus hirae ( UniProt P39046 ) and Listeria monocytogenes ( UniProt Q8Y842 , PDB  3fi7 ), which are structurally similar to Lysozymes the regulation and function of bacterial peptidoglycan hydrolases. The review by S. Layec gives an overview. Lytic transglycosylases appear to be an important group of bacterial autolysins. They occur ubiquitously in eubacteria , with the exception of mycoplasma . On the basis of sequence and consensus motifs, four families are distinguished that are required for different functions. As far as is known, bacterial lytic transglycosylases have exo activity, i. i.e. they cleave disaccharide anhydromuropeptides from reducing or non-reducing ends of the peptidoglycan. They are involved in cell growth and division. They enable the incorporation of protein complexes such as flagella and pili , which are integrated into the peptidoglycan cell wall.

Function of lysozymes in fungi

Since the lysozyme of the fungus Chalaropsis sp. is produced as an extracellular bacteriolytic enzyme, it is likely to act as a bacteriocin .

Activity determination

The natural substrate of lysozymes is an insoluble peptidoglycan polymer with a high molar mass , which usually strengthens the cell wall of bacteria so that they can withstand the high internal cell pressure. This large biopolymer is often used to measure lysozyme activity. For this purpose, for example, dried and UV- inactivated cells from Micrococcus luteus are used. Due to the insolubility and complexity of the substrate, the reaction kinetics cannot be described as Michaelis-Menten kinetics .

For specific measurements of the lysozyme activity either special substrates have to be used or the products have to be examined. To avoid problems with the insolubility and heterogeneity of the substrate in cells or cell wall preparations, soluble oligosaccharides and muropeptides are also used.

Usually one of the following three non-specific methods is used.

Turbidity measurement (light scattering)

The decrease in the optical density of a cloudy cell suspension is monitored photometrically at 650, 520 or 450 nm.

Viscosity measurement

The increase in viscosity due to the depolymerization of the insoluble peptidoglycans into soluble glycopeptides is monitored.

Lysoplate assay

Killed bacterial cells are added to a one percent agar solution and this is plated out in Petri dishes . After the agar solution has solidified, wells are pressed into the agar and the enzyme samples are added to them. As a result of the enzyme action, transparent zones form around the depression in the previously cloudy agar. The diameter of these zones is determined.

Other methods

Analogous to the turbidity measurements, there are measurements with radioactive or color-marked substrates. These are also unspecific.

Resistance Mechanisms

N-deacetylation and O-acetylation are common modifications of peptidoglycan in pathogenic bacteria that contribute to lysozyme resistance, at least in Listeria monocytogenes and Staphylococcus aureus . Another strategy is the production of lysozyme inhibitors, as in the periplasm of E. coli ( UniProt P0AD59 , PDB  1GPQ ) or bound to the outer membrane as in Pseudomonas aeruginosa ( UniProt Q9I574 , PDB  3F6Z ).

Inhibitors

Imidazole , Indole , NAG , (NAG) 2 , (NAG) 3

properties

Animal lysozymes are globular proteins that are divided into two domains by a large substrate-binding cleft , a larger α-helical domain containing the amino and carboxy terminus of the protein, and a smaller β-sheet domain. This type of mixed α + β fold is called a lysozyme-like fold . There are eight conserved cysteine ​​residues in c-type lysozymes that form four disulfide bridges . G-type lysozymes in mammals and birds have four to seven cysteine ​​residues, but some fish have only one or no cysteine ​​residues, and invertebrates six to thirteen cysteine ​​residues, none of which are the same as those in mammals and birds. Nothing is known about the presence and location of disulfide bridges in g-type lysozymes from invertebrates. A high proportion of cysteine ​​residues appears to be typical in i-type lysozymes. In the lysozyme of the clam Venerupis philippinarum , for example, all 14 cysteine ​​residues form disulfide bridges. The animal c- and i-type lysozymes are about 11 to 15 kDa, and g-type lysozymes are about 20 to 22 kDa. The isoelectric points of the c- and g-type lysozymes calculated from the sequence are in the basic range , those of the i-type lysozymes are more variable. C- and i-type lysozymes involved in digestion usually have a pI in the neutral or acidic range .

CH-type lysozymes and h-type chitinases have structures of an α / β hydrolase folding type that can be assigned to the TIM barrel fold . They are about 22 to 40 kDa in size, with the larger, in addition to the lysozyme domain, also having several independently folding domains which have a substrate-binding function, such as in the case of the Streptococcus phage Cp-1 . Modular proteins can also be found in bacteria.

The v-, λ- and g-type viral lysozymes are often around 17 to 19 kDa in size. There are also larger lysozymes bound to virus particles that are involved in the infection.

Reaction mechanisms

Muramidase activity using the example of HEWL

HEWL is an endoglycosidase that hydrolyzes β-1,4-glycosidic bonds between NAM and NAG residues in peptidoglycan, whereby the anomeric configuration at C1 of the NAM residue is retained. Peptidoglycan is bound in the bond gap between the α-helical and β-sheet domains, which is six saccharide units long. The binding sites of the individual sugar residues are designated A (-4), B (-3), C (-2), D (-1), E (+1) and F (+2). For steric reasons, no N-acetylmuramic acid residue fits into the binding site C (-2), so that the NAM residues are in positions B (-3), D (-1) and F (+2) when binding to peptidoglycan have to. The binding creates a kink in the polysaccharide chain, which probably forces the conformation of the NAM residue in position D (-1) into a half-chair conformation. The enzyme hydrolyzes the β-1,4-glycosidic bond between position D (-1) and E (+1). In the first step, the oxygen of the glycosidic bond is protonated by the glutamic acid residue Glu35 of the HEWL and the part of the substrate bound in positions E (+1) and F (+2) could loosen and diffuse away.

According to the mechanism postulated by David C. Phillips, a glycosyloxocarbenium ion would arise as an intermediate from the NAM residue, the α side of which is shielded and stabilized by the aspartate residue Asp52 of the HEWL. In a second step, a proton would be withdrawn from a water molecule through the glutamate residue Glu35 that is now present, and the resulting hydroxide ion would nucleophilically attack the C1 atom of the NAM residue from the β side. The second hydrolysis product would result, with the configuration of the anomeric center at C1 of the NAM residue being retained.

More recent work has shown that the oxocarbenium ion is not an intermediate, but the transition state to an intermediate covalently bound via the aspartate residue Asp52. Analogous to the originally formulated reaction mechanism, this covalently bound intermediate is nucleophilically attacked by a hydroxide ion from the β side on the C1 atom. The original configuration of the anomeric center at C1 of the NAM residue is restored by the formation of the second hydrolysis product.

Muramidase activity in g-type lysozymes and T4 lysozyme

In contrast to the hydrolysis reaction by HEWL, the hydrolysis of g-type lysozymes from goose (GEWL) and cod (gLYS) is accompanied by an inversion of the anomeric center on the C1 atom of the N-acetylmuramic acid residue. Analogous to Glu35 (HEWL), the glutamic acid residue Glu73 (GEWL & gLYS) is essential for hydrolysis, a second acidic amino acid residue such as Asp52 (HEWL) near the C1 atom of the NAM residue in position D (-1) is missing in both of them g-type lysozymes. Instead, two aspartate residues (Asp86 / 97 in GEWL; Asp90 / 101 in gLYS) are likely to position a water molecule near the C1 atom, which takes on the function of Asp52 (HEWL). In T4L, Glu11 is the essential glutamic acid residue, the aspartate residue Asp20 and the threonine residue Thr26 bind a water molecule near the C1 atom that can attack it.

Transglycosylation activity

In HEWL, the covalently bound intermediate can react with saccharides instead of water, so that transglycosylation takes place instead of hydrolysis. By exchanging the threonine residue Thr26 for a histidine residue in the T4 lysozyme, this is converted by an inverting muramidase into a transglycosidase.

Lytic transglycosylase

Lytic transglycosylases cleave the same bond as N-acetylmuramidases, producing 1,6-anhydro-N-acetylmuramic acid as a product. Structures that provide insight into the reaction mechanism are available for gp144 and Slt35, for example.

Chitinase activity from HEWL

Like a number of other lysozymes, HEWL can hydrolyze the β-1,4-glycosidic bonds in chitin and in the water-soluble oligosaccharides (chitodextrins) made from chitin.

More functions

In addition to the lysozyme activity, isopeptidase activity was found in some i-type lysozymes. They hydrolyze the isopeptide bonds that were formed between the γ-carboxamide group of a glutamine residue and the ε-amino group of a lysine residue. These are formed, for example, between fibrin molecules by the fibrin stabilizing factor . This activity has been demonstrated in the leech , for example, and prevents the blood from coagulating. It is still unclear whether this function is also important in other invertebrates or whether the isopeptide bonds of some peptidoglycans are split.

Extraction

Crystallizing lysozyme in a drop.

HEWL is obtained from the egg white of chicken eggs and is freeze-dried. More than 100 tons are produced annually. The lysozyme from Streptomyces coelicolor is also obtained in larger quantities by submerged fermentation and marketed ( Cellosyl ® ). Human lysozyme is obtained from neutrophilic granulocytes, from milk and recombinantly , for example from genetically modified rice . It is now also possible to extract human lysozyme C from the milk of cows.

use

In the food industry, lysozyme is used for preservation or, for example, in winemaking to control the malolactic fermentation . As a preservative, it is approved in the EU as a food additive with the number E 1105 for aged cheese and for preserving beer that has neither been pasteurized nor sterile-filtered. In cheese, the formation of cracks in the cheese crumb (so-called late bloating) is prevented by Clostridium tyrobutyricum or Clostridium botulinum .

Lactic acid bacteria should be prevented from developing in beer. Most breweries apply sterile filtration or pasteurization to their beer to prevent bacterial spoilage during storage prior to consumption. With some beer specialties, such as top-fermented, post-fermentation beers, z. B. draft or bottled beer, these processes cannot be used because the viable microorganisms present in these beers are part of the manufacturing process.

One area of ​​application currently being developed is the use of HEWL in so-called “active” food packaging to extend the shelf life of certain foods. There are transgenic goats, pigs and cattle that produce human lysozyme in their milk and that are expected to improve animal health, increased food safety and shelf life.

Lysozyme is used to break down bacterial cells. To break down gram-negative bacteria with HEWL, EDTA can be added to permeabilize the outer membrane .

In addition, the heterologous expression of human lysozyme in plants can lead to increased resistance to bacteria and fungi.

Clinical significance

A connection between reduced lysozyme activity and bronchopulmonary dysplasia in newborns is suspected. Small children who lack lysozyme in their diet are more likely to develop diarrhea. Defensins and lysozyme protect the conjunctiva of the eye from bacteria, so that deficits can lead to conjunctivitis . Mutations in the LYZ gene can lead to the very rare familial amyloidosis .

Increased lysozyme concentrations in the blood serum occur in chronic bacterial infections such as tuberculosis , sarcoidosis , Crohn's disease , AIDS , rheumatoid arthritis and monocytic and monomyelocytic leukemia . In the case of urinary tract infections, certain kidney damage and excessive endogenous lysozyme production that exceeds the reabsorption capacity of the proximal tubule, increased lysozyme levels in the urine can be detected. In bacterial meningitis and in tumors of the central nervous system, increased values ​​can be detected in the cerebrospinal fluid. In bacterial meningitis, for example, values ​​that are 5 to 400 times higher can be determined. In inflammatory diseases of the gastrointestinal tract, such as Crohn's disease, in gastroenteritis due to bacterial or rotavirus infections and in colon cancer , increased amounts of lysozyme have been detected in the feces . The lysozyme concentration can also be increased in saliva. In these cases, the lysozyme concentration or amount can serve as a marker to follow the course of the disease, to assess the success of the therapy and to determine relapses.

In the publications by Brouwer et al. a. (1984) and Porstmann et al. a. (1989) the following reference ranges were given for lysozyme.

serum

  • Newborns 800–4600 µg / l
  • Adults (18–40 years) 450–2950 µg / l
  • Adults (41–70 years) 1100–2900 µg / l
  • Adults (18–60 years) 950–2450 µg / l

urine

  • Women 0.45–20.1 µg / l
  • Men 0.33–6.4 µg / l
  • 1.7-123 µg / l

Cerebrospinal fluid

  • 17.6-118 µg / l

Feces

  • 0.04-1.5 µg / g

The therapeutic effectiveness of lysozyme (HEWL) is based on the one hand on its enzymatic activity, which allows the growth of sensitive bacteria to be controlled. In addition, lysozyme modulates the immune response to infections, stimulates the immune system and has anti-inflammatory effects. As a result, it works against viral infections, increases the effectiveness of antibiotics and can be used in the treatment of cancer and a weakened immune system. Lysozyme is usually given orally. Lysozyme is found in some sore throat tablets. However, there is no real proof of effectiveness here. Lysozyme from chicken eggs can trigger a reaction if you are allergic to egg white .

literature

Web links

Individual evidence

  1. ↑ a b Pierre Jolles, Jacqueline Jolles: What's new in lysozyme research? Always a model system, today as yesterday . In: Molecular and Cellular Biochemistry . tape 63 , no. 2 , September 1984, pp. 165-189 , doi : 10.1007 / BF00285225 , PMID 6387440 .
  2. ↑ P. Lashchenko: About the germicidal and development- inhibiting effects of chicken protein . In: Journal of Hygiene and Infectious Diseases . tape 64 , no. 1 , December 1909, p. 419-427 , doi : 10.1007 / BF02216170 .
  3. ↑ a b A. Fleming: On a Remarkable Bacteriolytic Element Found in Tissues and Secretions . In: Proceedings of the Royal Society B: Biological Sciences . tape 93 , no. 653 , May 1, 1922, p. 306-317 , doi : 10.1098 / rspb.1922.0023 .
  4. ↑ Robert E. Canfield: The Amino Acid Sequence of Egg White Lysozyme . In: The Journal of biological chemistry . tape 238 , no. 8 , August 1963, p. 2698-2707 , PMID 14063294 ( jbc.org ).
  5. ↑ CCF Blake, DF Koenig, GA Mair, ACT North, DC Phillips, VR Sarma: Structure of Hen Egg-White Lysozyme: A Three-dimensional Fourier Synthesis at 2 Å Resolution . In: Nature . tape 206 , no. 4986 , May 22, 1965, p. 757-761 , doi : 10.1038 / 206757a0 , PMID 5891407 .
  6. ^ Louise N. Johnson, David C. Phillips: Structure of Some Crystalline Lysozyme-Inhibitor Complexes Determined by X-Ray Analysis At 6 Å Resolution . In: Nature . tape 206 , no. 4986 , May 22, 1965, p. 761-763 , doi : 10.1038 / 206761a0 , PMID 5840126 .
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