Lysozyme is a small antimicrobial protein that your body produces as a frontline defense against bacteria. Found in tears, saliva, nasal mucus, and breast milk, it works by breaking apart bacterial cell walls, effectively popping bacteria like overfilled balloons. Beyond its role in human immunity, lysozyme has found its way into food preservation, winemaking, wound care research, and even the fight against antibiotic-resistant superbugs. It also holds a special place in the history of science as the first enzyme whose three-dimensional structure was ever solved.
How Lysozyme Destroys Bacteria
Bacterial cell walls are held together by a mesh-like molecule called peptidoglycan, which gives bacteria their structural rigidity. Lysozyme acts like molecular scissors, cutting the bonds that hold this mesh together. Specifically, it slices the connection between two sugar building blocks in peptidoglycan, weakening the wall until the bacterium bursts open from its own internal pressure.1PubMed Central. Lysozyme and Its Application as Antibacterial Agent in Food Industry This enzymatic chopping is effective against many types of bacteria, particularly those classified as Gram-positive, whose thick peptidoglycan layer is directly exposed to the enzyme.2PubMed. The disruptive effect of lysozyme on the bacterial cell wall explored by an in-silico structural outlook
What makes lysozyme more versatile than a one-trick enzyme, though, is that it can also kill microbes without any enzymatic activity at all. Researchers have shown that even when lysozyme is heat-denatured (meaning its enzyme function is completely destroyed), it still retains antimicrobial power. Certain stretches of the protein form structures that can punch through bacterial and fungal cell membranes directly, acting more like a detergent than a pair of scissors. Small synthetic peptides matching these membrane-disrupting regions of lysozyme can kill bacteria on their own, yet they do not damage red blood cells, suggesting a degree of selectivity.3PubMed. The non-enzymatic microbicidal activity of lysozymes This dual mechanism means lysozyme can tackle a broader range of threats than its enzymatic action alone would allow.
Where Your Body Keeps Lysozyme
Lysozyme is a roughly 14-kilodalton protein present across a wide range of body fluids and tissues. It shows up in tears, saliva, nasal secretions, and the mucus lining the respiratory and gastrointestinal tracts, and it plays an active role in innate immunity against bacteria, viruses, and fungi.4PubMed Central. Applications of Lysozyme, an Innate Immune Defense Factor, as an Alternative Antibiotic It is also produced by certain white blood cells and by liver cells.5PubMed. Hereditary lysozyme amyloidosis — phenotypic heterogeneity and the role of solid organ transplantation Its presence in tears is one reason your eyes can fend off infection despite constant exposure to airborne bacteria.
Lysozyme does not work in isolation. In body fluids, it teams up with another antimicrobial protein called lactoferrin. Neither protein is particularly lethal to Gram-negative bacteria on its own, because those bacteria have an outer membrane that shields their peptidoglycan from lysozyme’s reach. But lactoferrin strips away that protective membrane by binding iron the bacteria need, and once the shield is down, lysozyme can get to work. Together, the two proteins become genuinely bactericidal against pathogens like Vibrio cholerae, Salmonella, and E. coli, when individually they would only slow growth.6The Journal of Clinical Investigation. Killing of gram-negative bacteria by lactoferrin and lysozyme Saturating lactoferrin with iron reverses this synergy, confirming that it depends on lactoferrin starving bacteria of iron.7PubMed. Synergic antistaphylococcal properties of lactoferrin and lysozyme
Chicken Eggs and Other Natural Sources
If you have ever wondered where commercial lysozyme comes from, the answer is almost always chicken eggs. About 3.5% of chicken egg white is lysozyme, making it one of the richest natural sources of the enzyme.8European Food Research and Technology. Lysozyme separation from chicken egg white: a review Hen egg white lysozyme (often abbreviated HEWL in research papers) has been the workhorse of lysozyme research and industrial application for decades. It is relatively easy to extract and purify, and it is the version used in most food-preservation and winemaking applications.
Human breast milk is another significant source. The lysozyme concentration in breast milk is far higher than in cow’s milk, which is one reason lysozyme has been studied as a supplement for infant formula. Adding lysozyme to formula makes it more closely resemble human milk in its antimicrobial profile.9PubMed. The chemistry of lysozyme and its use as a food preservative and a pharmaceutical The enzyme is also found in the tissues and secretions of many other animals, in plants, and even in some bacteriophages (viruses that infect bacteria).
How Bacteria Fight Back
Given that lysozyme has been part of animal immune defenses for hundreds of millions of years, bacteria have had plenty of time to evolve countermeasures. One of the most common strategies is chemical modification of peptidoglycan so that lysozyme can no longer grip its target. Research on Clostridioides difficile, a major cause of hospital-acquired diarrheal illness, identified two enzymes that remove specific chemical groups from the bacterium’s cell wall. Knocking out either one modestly reduces lysozyme resistance, but eliminating both causes a dramatic thousand-fold drop in resistance. The finding confirms that chemical modification of peptidoglycan is the primary defense C. difficile uses against lysozyme.10PubMed Central. Lysozyme Resistance in Clostridioides difficile Is Dependent on Two Peptidoglycan Deacetylases
Other bacteria use different tricks: some coat their cell walls with extra layers of teichoic acids, some produce proteins that directly inhibit lysozyme, and Gram-negative bacteria rely on their outer membrane as a physical barrier. These resistance mechanisms are an important reason why lysozyme alone is not a cure-all antibiotic, and why researchers have focused on combining it with other agents.
Lysozyme in Food and Winemaking
The food industry has used lysozyme for decades, particularly in cheese and wine production. In cheesemaking, lysozyme is added to prevent an unwanted fermentation called “late blowing,” caused by Clostridium bacteria that produce gas and off-flavors in aged cheeses. Because the enzyme is a natural protein rather than a synthetic chemical, it appeals to producers looking for cleaner labels.
In winemaking, lysozyme controls lactic acid bacteria that can trigger undesirable fermentation. This is especially relevant in biological aging of sherry wines, where lactic acid bacteria can produce volatile acidity that ruins the wine’s character. Adding lysozyme at a specific dose successfully suppresses these bacteria, and when used alongside the traditional flor yeast, it reduces volatile acidity as well.11Food Control. Use of lysozyme for the prevention and treatment of heterolactic fermentation in the biological aging of sherry wines That said, wine’s own chemistry can work against the enzyme. Phenolic compounds naturally present in red wine inhibit lysozyme’s activity, which means the enzyme works better in white wine production where phenolic levels are lower.12PubMed. The inhibitory effects of wine phenolics on lysozyme activity against lactic acid bacteria
There is a safety wrinkle worth knowing about. Lysozyme used in food comes from egg whites, and it is a recognized egg allergen. People with egg allergies can react to lysozyme in wine or cheese, sometimes without realizing the source. Regulatory agencies in many countries require lysozyme to be declared on labels when it exceeds trace levels.13PubMed. Immunological behavior of in vitro digested egg-white lysozyme
Wound Healing and Drug Delivery
Lysozyme’s antimicrobial properties have made it an attractive candidate for wound care, though getting it to work well at a wound site is more complicated than simply smearing it on. The enzyme degrades quickly when exposed to wound fluid, and keeping it active over the hours or days needed for wound healing requires specialized delivery systems. Researchers have explored four main approaches: hydrogels, thin nanofilms, electrospun fiber membranes, and chemically modified lysozyme composites. These carrier systems stabilize the protein and release it gradually at the wound, overcoming the limitations of direct application.14PubMed Central. Exploring the therapeutic potential of recombinant human lysozyme: a review on wound management system with antibacterial
Animal studies have shown promise. A lysozyme-loaded cream tested on scald wounds prevented infection by Staphylococcus aureus and promoted healing, with no toxicity detected in organ tissue.15PubMed. Antibacterial activity of lysozyme-loaded cream against MRSA and promotion of scalded wound healing Electrospun patches designed to stick to the lining of the mouth have delivered lysozyme that remained biologically active and inhibited oral bacteria, pointing toward applications for treating mouth infections or post-surgical care.16Materials Science and Engineering: C. Incorporation of lysozyme into a mucoadhesive electrospun patch for rapid protein delivery to the oral mucosa The technology has even extended beyond infection control: lysozyme nanofibrils combined with gelatin have been electrospun into cardiac patches designed for heart tissue regeneration, taking advantage of the nanofibrils’ mechanical strength and antioxidant properties.17Advanced Functional Materials. Gelatin‐Lysozyme Nanofibrils Electrospun Patches with Improved Mechanical, Antioxidant, and Bioresorbability Properties for Myocardial Regeneration Applications
Despite all this promising work, lysozyme is not yet a standard wound-care drug. Clinical trials in humans remain limited, and most of the evidence comes from laboratory or animal models. The challenge of scaling up production, ensuring shelf stability, and navigating regulatory approval keeps lysozyme-based wound products in the research pipeline rather than on pharmacy shelves for now.
Lysozyme and the Antibiotic Resistance Crisis
One of the most active areas of lysozyme research involves combining it with conventional antibiotics to fight drug-resistant bacteria. The logic is straightforward: if lysozyme weakens the bacterial cell wall from one angle while an antibiotic attacks from another, bacteria that have evolved resistance to either one alone might still be killed by the combination.
Recent work has explored this idea from several directions. A 2025 study found that when lysozyme is paired with the antibiotic tigecycline, the two form a stable complex that delivers the drug more effectively against E. coli. Interestingly, a different antibiotic (doxycycline) binds lysozyme more weakly and is released prematurely, reducing the benefit, even though doxycycline is the stronger antibiotic on its own. The takeaway is that binding strength matters for these partnerships to work.18PubMed. Formation Mechanism and Antibacterial Activity of Natural Antimicrobial Lysozyme with Antibiotics Doxycycline and Tigecycline
Another study took the approach from the antibiotic’s side: the common antibiotic cefdinir was shown to reprogram the cell walls of Gram-positive superbugs, making them more negatively charged and therefore more vulnerable to lysozyme. The combination not only killed multi-drug-resistant bacteria but also suppressed biofilm formation and reduced the likelihood of new resistance mutations emerging. In rat skin infection models, the combination therapy performed well, demonstrating translational potential.19PubMed Central. Cefdinir reprograms Gram-positive bacteria to synergize with lysozyme against superbugs
The principle extends beyond human medicine. A lysozyme derived from a crab species showed synergistic or additive effects when combined with tetracycline and fluoroquinolone antibiotics against multi-drug-resistant marine bacteria, and it appeared to suppress the expression of antibiotic resistance genes.20PubMed. Antibacterial activity and mechanism of a crab-derived i-type lysozyme against multidrug-resistant Vibrio alginolyticus If lysozyme-antibiotic combinations can be shown to reliably overcome resistance while minimizing new resistance, the approach could become a meaningful tool in a post-antibiotic world.
Making Lysozyme Without Chickens
Extracting lysozyme from millions of chicken eggs works, but it is not ideal if you need human lysozyme (which differs from the hen version) or if you need it in quantities that the egg supply chain cannot easily provide. Scientists have developed transgenic plants, animals, and microorganisms that can produce human lysozyme, and microbial systems have emerged as the most practical route for commercial-scale production.21PubMed. Recent advances for the production and recovery methods of lysozyme
Yeast has been the workhorse organism. One team engineered the yeast Pichia pastoris to carry six copies of an optimized human lysozyme gene, then boosted production further by co-expressing molecular chaperone proteins that help the lysozyme fold correctly. The result was about a 2.4-fold improvement in protein yield and a 2.3-fold boost in antibacterial activity compared to their starting strain. Scaled up in a fermenter, the system reached substantial production levels.22PubMed Central. A Combinational Strategy for Effective Heterologous Production of Functional Human Lysozyme in Pichia pastoris More recently, researchers discovered that deliberately disrupting genes involved in cell division in a related yeast species caused cells to grow larger and secrete dramatically more lysozyme, achieving the highest reported yeast-based production of human lysozyme to date.23PubMed Central. Cytokinetic engineering enhances the secretory production of recombinant human lysozyme in Komagataella phaffii
Recombinant production is not just an academic exercise. If lysozyme-based wound products or antibiotic combinations eventually reach clinical use, they will likely rely on human lysozyme rather than the hen egg version, both for efficacy and to avoid egg-allergen concerns. Having scalable microbial production in place will be essential.
When Lysozyme Goes Wrong
Like many proteins, lysozyme can misfold. In a rare inherited condition called hereditary lysozyme amyloidosis, mutations in the lysozyme gene cause the protein to adopt abnormal shapes that aggregate into insoluble fibers called amyloid fibrils. These fibrils accumulate in organs, particularly the kidneys, liver, and gastrointestinal tract, and gradually impair their function. The disease follows an autosomal dominant inheritance pattern, meaning a single mutated copy of the gene is enough to cause problems.5PubMed. Hereditary lysozyme amyloidosis — phenotypic heterogeneity and the role of solid organ transplantation
Structural studies have shed light on what goes wrong at the molecular level. One cryo-electron microscopy study resolved the structure of a lysozyme amyloid fibril at near-atomic detail, isolated from a patient carrying a specific mutation. The fibril core included all 130 amino acids of the protein, and four of the protein’s disulfide bonds connected the same residue pairs as in the normal folded protein, but the overall shape was fundamentally different from healthy lysozyme. This suggests that the protein has to unfold significantly before it can refold into the pathological fibril shape.24Nature Communications. Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis Different mutations lead to different clinical presentations, and organ transplantation has been explored as a treatment for severely affected patients, though the disease remains rare enough that large clinical trials do not exist.
A Stomach Full of Lysozyme
One of the more surprising chapters in lysozyme biology comes from ruminants like cows, sheep, and deer. These animals have repurposed lysozyme as a digestive enzyme. In their multi-chambered stomachs, bacteria ferment plant material and are then passed to downstream chambers where they are digested. Lysozyme breaks open the bacterial cells, releasing the nutrients inside. It is an elegant recycling system: bacteria do the hard work of breaking down cellulose, and the cow harvests the bacteria.
To make this work, ruminant genomes expanded their lysozyme gene family through duplication. Cow and sheep genomes carry roughly ten lysozyme genes, about four of which are expressed specifically in the stomach.25PubMed. Mosaic evolution of ruminant stomach lysozyme genes These duplications happened around 40 to 50 million years ago, and the coding regions of the stomach lysozyme genes have since evolved in a coordinated fashion within each species, keeping the stomach versions similar to one another even as the non-coding regions drifted apart freely.26Journal of Biological Chemistry. Concerted evolution of ruminant stomach lysozymes. Characterization of lysozyme cDNA clones from sheep and deer This coordinated evolution may have helped early ruminants rapidly adapt lysozyme to function in the acidic, enzyme-rich stomach environment.27PubMed Central. Genomic organization and evolution of ruminant lysozyme c genes
Lysozyme’s Place in the History of Science
Alexander Fleming discovered lysozyme in 1922, several years before his more famous discovery of penicillin. Fleming noticed that his own nasal mucus could dissolve bacteria on a culture plate, and he traced the effect to a substance he named lysozyme (from “lysis,” meaning breaking apart, and “enzyme”).28PubMed Central. Observations on a Bacteriolytic Substance (“Lysozyme”) Found in Secretions and Tissues Fleming considered lysozyme more interesting than penicillin for much of his career, though history obviously remembered the antibiotic more fondly.
Lysozyme earned another landmark in the 1960s when it became the first enzyme whose three-dimensional structure was determined by X-ray crystallography.29PubMed. X-ray crystallography of the binding of the bacterial cell wall trisaccharide NAM-NAG-NAM to lysozyme30PubMed Central. 100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology David Phillips and colleagues solved the structure of hen egg white lysozyme in 1965, providing the first atomic-level picture of how an enzyme’s shape relates to its function. That work laid the groundwork for modern structural biology and drug design. Even today, lysozyme remains one of the most commonly used model proteins in biochemistry courses and crystallography experiments, in part because it crystallizes easily and behaves predictably. It is, in a sense, the fruit fly of protein science.