Lysozyme Functionality in Innate Immune Systems

Lysozymes are ubiquitous antimicrobial enzymes that serve as a first line of defence across the animal kingdom. By hydrolysing the β-1,4 linkages between N-acetylmuramic acid and N-acetylglucosamine in bacterial peptidoglycan, they compromise cell‐wall integrity and trigger rapid lysis of susceptible microbes. Three principal families have been identified: chicken-type (c-type), goose-type (g-type) and invertebrate-type (i-type), each differing in sequence, structure and spectrum of activity. Beyond direct bacteriolysis, lysozymes modulate inflammatory responses, influence microbiota composition at mucosal surfaces and contribute to antiviral and antitumour activities in vertebrates. Evolutionary gene duplications and positive selection have driven diversification of lysozyme paralogues, allowing specialised functions—from digestive processes in ruminants to mucosal immunity in fish and invertebrates. Research has also revealed bacterial countermeasures, such as specific protein inhibitors, underscoring an ongoing arms race. In agriculture and aquaculture, lysozyme activity is explored as a biomarker of health and as a prospective alternative to antibiotics. Advances in recombinant production and inhibitor profiling promise novel diagnostic and therapeutic applications, offering broad potential for enhancing disease resistance in both wild and farmed species.

Research from Nature Portfolio

Recent studies have revealed an unprecedented absence of c-type lysozyme genes in Atlantic cod, a feature unique among vertebrates. In contrast, multiple g-type lysozyme paralogues were identified, each differentially expressed across tissues and responsive to bacterial infection and cytokine signalling. Serial gene duplications have yielded both enzymatically active and inactive variants, the latter possibly functioning in non-catalytic immune roles. Differential regulation of these paralogues during challenge with intracellular pathogens suggests specialised compensatory mechanisms that maintain antibacterial defence despite loss of a canonical lysozyme family member.

Research from all publishers

A novel inhibitor-based affinity chromatography approach has enabled rapid typing and profiling of c-, g- and i-type lysozymes in complex biological fluids. Application to the blue mussel revealed active g-type lysozyme in haemolymph and characterised its specific role in controlling Aeromonas and E. coli strains, while demonstrating the absence of detectable c-type activity. In penaeid shrimp, in vivo silencing of the c-type lysozyme via RNA interference led to dramatic loss of circulating haemocytes, unchecked bacterial proliferation and 100% mortality in the absence of challenge. Rescue by antibiotic treatment confirmed that mortality stemmed from bacterial overgrowth, firmly establishing the essential regulatory role of lysozyme in crustacean innate immunity.

Lysozyme Functionality in Innate Immune Systems publication trend

The graph below shows the total number of articles in lysozyme functionality in innate immune systems across all publications each year (not limited to Nature Index journals).

Technical terms

Lysozyme: An enzyme that cleaves the β-1,4 glycosidic bonds in bacterial peptidoglycan, leading to cell lysis.

Peptidoglycan: A polymer of sugars and amino acids forming a mesh-like layer outside bacterial plasma membranes.

Haemolymph: The circulatory fluid in invertebrates analogous to blood, containing immune cells and soluble factors.

Isozyme: One of several enzyme variants that catalyse the same reaction but differ in sequence or regulation.

Gene duplication: An evolutionary event in which a genomic region is copied, allowing paralogues to acquire new or specialised functions.

References

1. Lysozyme Inhibitors as Tools for Lysozyme Profiling: Identification and Antibacterial Function of Lysozymes in the Hemolymph of the Blue Mussel. Molecules (2023).
2. Functional Analysis of C-type Lysozyme in Penaeid Shrimp*. Journal of Biological Chemistry (2011).
3. Multiple specialised goose-type lysozymes potentially compensate for an exceptional lack of chicken-type lysozymes in Atlantic cod. Scientific Reports (2016).