LYZ is the single chicken-type (c-type) lysozyme of the common vampire bat, a secreted glycoside hydrolase of family GH22 (EC 3.2.1.17). The 148-residue precursor has a signal peptide (residues 1-18) and a cleaved 19-148 mature chain that adopts the canonical lysozyme C fold. It hydrolyses the beta-(1->4) linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine in bacterial peptidoglycan, and between N-acetylglucosamine residues in chitodextrins, degrading the cell wall and lysing the bacterium. Its physiological setting is extracellular: it is a classical innate immune effector of body fluids and secretions, and in D. rotundus it is one of the antimicrobials that dominate the accessory submaxillary salivary gland, where it was detected at both transcript and protein level, and it is also transcribed in liver. Unlike insectivorous bats, which duplicated and neofunctionalised lysozyme for chitin digestion, vampire bats retain a single lysozyme gene; that gene carries a signature of positive selection on the mature protein specific to the sanguivorous lineage, with substitutions predicted to alter function, consistent with adaptation of antimicrobial defence to a blood diet.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003796 lysozyme activity | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt records the EC 3.2.1.17 reaction for this protein, it is assigned to glycosyl hydrolase family 22, and PANTHER places it in subfamily PTHR11407:SF28 LYSOZYME C. Muramidase activity is the core molecular function. Reason: Catalytic activity statement, GH22 family assignment, and lysozyme C subfamily assignment all agree. This is the defining activity of the protein. Supporting Evidence: file:DESRO/K9IWH5/K9IWH5-uniprot.txt Hydrolysis of (1->4)-beta-linkages between N-acetylmuramic file:DESRO/K9IWH5/K9IWH5-uniprot.txt Belongs to the glycosyl hydrolase 22 family. |
| GO:0003824 catalytic activity | IEA GO_REF:0000043 | MODIFY | Summary: Root-level catalytic activity derived from the Hydrolase keyword. The specific reaction is known and already annotated. Reason: Replace with the specific GO:0003796 lysozyme activity. Proposed replacements: lysozyme activity Supporting Evidence: file:DESRO/K9IWH5/K9IWH5-uniprot.txt Hydrolysis of (1->4)-beta-linkages between N-acetylmuramic |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | MODIFY | Summary: Keyword-derived parent term. The exact hydrolytic reaction is specified in the UniProt catalytic activity block. Reason: Replace with the specific GO:0003796 lysozyme activity. Proposed replacements: lysozyme activity Supporting Evidence: file:DESRO/K9IWH5/K9IWH5-uniprot.txt Hydrolysis of (1->4)-beta-linkages between N-acetylmuramic |
| GO:0016798 hydrolase activity, acting on glycosyl bonds | IEA GO_REF:0000043 | MODIFY | Summary: Keyword-derived intermediate parent. Correct but two levels more general than the annotated EC 3.2.1.17 reaction. Reason: Replace with the specific GO:0003796 lysozyme activity. Proposed replacements: lysozyme activity Supporting Evidence: file:DESRO/K9IWH5/K9IWH5-uniprot.txt Hydrolysis of (1->4)-beta-linkages between N-acetylmuramic file:DESRO/K9IWH5/K9IWH5-uniprot.txt Belongs to the glycosyl hydrolase 22 family. |
| GO:0050830 defense response to Gram-positive bacterium | IEA GO_REF:0000118 | ACCEPT | Summary: Gram-positive bacteria are the canonical target of c-type lysozymes, because their thick peptidoglycan is directly accessible to the enzyme. The human orthologue LYZ carries this annotation from direct assay (IDA), and the TreeGrafter propagation to the bat protein is appropriate. An earlier version of this review proposed replacing this term with the broader GO:0042742; that would discard information, since the general term is separately annotated and retained. Reason: This is the well-supported, mechanistically explained specificity of c-type lysozyme, and the broad parent is annotated separately. Keep the specific term. Supporting Evidence: file:DESRO/K9IWH5/K9IWH5-uniprot.txt Lysozymes have primarily a bacteriolytic function file:DESRO/K9IWH5/K9IWH5-deep-research-falcon.md GH22 lysozymes prefer Gram-positive bacteria due to accessibility of peptidoglycan, but they can exhibit activity against Gram-negative bacteria when the outer membrane barrier is compromised |
| GO:0050829 defense response to Gram-negative bacterium | IEA GO_REF:0000118 | ACCEPT | Summary: Activity against Gram-negative bacteria is the secondary, well-described behaviour of mammalian c-type lysozymes: the outer membrane shields the peptidoglycan, so killing requires permeabilisation, but the activity is real and the human orthologue carries the same annotation by phylogenetic inference. As with the Gram-positive term, an earlier version of this review proposed generalising this to GO:0042742, which would lose the distinction between the primary and secondary spectrum. Reason: Consistent with the characterised spectrum of mammalian c-type lysozyme and with the same TreeGrafter propagation applied to the human orthologue. Retained at the specific level. Supporting Evidence: file:DESRO/K9IWH5/K9IWH5-deep-research-falcon.md GH22 lysozymes prefer Gram-positive bacteria due to accessibility of peptidoglycan, but they can exhibit activity against Gram-negative bacteria when the outer membrane barrier is compromised file:DESRO/K9IWH5/K9IWH5-uniprot.txt Lysozymes have primarily a bacteriolytic function |
| GO:0042742 defense response to bacterium | IEA GO_REF:0000043 | ACCEPT | Summary: The general antibacterial defence term, correct as the umbrella over the two spectrum-specific terms above. Supported by the UniProt Antimicrobial and Bacteriolytic enzyme keywords and by the description of c-type lysozyme as an innate immune effector that kills bacteria by degrading their cell wall peptidoglycan. Reason: Correct and directly supported. Retained as the general parent alongside the specific Gram-positive and Gram-negative terms. Supporting Evidence: file:DESRO/K9IWH5/K9IWH5-uniprot.txt Lysozymes have primarily a bacteriolytic function PMID:31506780 killing bacteria by degrading peptidoglycan in their cell walls |
| GO:0031640 killing of cells of another organism | IEA GO_REF:0000043 | ACCEPT | Summary: This is precisely what a muramidase does: hydrolysing peptidoglycan weakens the cell wall and lyses the bacterium. The human orthologue LYZ carries this term from direct assay (IDA, PMID:9727055). An earlier version of this review marked it as over-annotated on the grounds that it is broad, but breadth is not the issue here - the term states the outcome of the enzyme's own catalytic action. Reason: Bacteriolysis is the direct, demonstrated consequence of lysozyme activity, not an inflated inference. The keyword source (Bacteriolytic enzyme) is exactly on point. Supporting Evidence: PMID:31506780 killing bacteria by degrading peptidoglycan in their cell walls file:DESRO/K9IWH5/K9IWH5-deep-research-falcon.md thereby weakening the cell wall and causing osmotic lysis |
| GO:0005576 extracellular region | ISS file:DESRO/K9IWH5/K9IWH5-uniprot.txt | NEW | Summary: Proposed new annotation. The GOA record for K9IWH5 carries no cellular component term at all, which is a genuine gap: the precursor has a SignalP-predicted signal peptide (1-18) with a cleaved 19-148 mature chain, lysozyme is a classical secreted protein of body fluids, the human orthologue is annotated to GO:0005576 from direct assay, and lysozyme was recovered from the D. rotundus accessory submaxillary gland by both transcriptome and proteome analysis. Reason: Fills a missing aspect. The ISS evidence code rests on the sequence and orthology basis recorded in the UniProt entry - the cleaved signal peptide and the secreted human orthologue - which is why the reference is the UniProt record rather than a publication. The Vampirome study is retained as corroborating support, but its proteome was taken from dissected gland tissue rather than secreted saliva, so it is not by itself direct evidence of extracellular localisation. Supporting Evidence: file:DESRO/K9IWH5/K9IWH5-uniprot.txt SIGNAL 1..18 PMID:23411029 families were expressed at higher levels in the AC gland, as indicated by both transcriptome and proteome analysis (Figure 2B). file:DESRO/K9IWH5/K9IWH5-deep-research-falcon.md These features support extracellular localization (secreted protein) as primary functional context. |
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Download this section (compressed HTML)Q: Do the positively selected substitutions in vampire bat mature lysozyme change its catalytic properties or antibacterial spectrum relative to lysozymes of insectivorous and frugivorous phyllostomid bats?
Suggested experts: David M. Irwin, Yang Liu
Q: Is salivary lysozyme delivered to the host bite wound in amounts that matter for wound microbiology, or does it act principally to protect the bat's own oral cavity and ingested blood meal?
Suggested experts: Ivo M. B. Francischetti, José M. C. Ribeiro
Q: Why is lysozyme concentrated in the accessory rather than the principal submaxillary gland, and does that compartmentalisation separate antimicrobial from anti-hemostatic salivary functions?
Experiment: Express recombinant D. rotundus LYZ alongside lysozyme from a frugivorous phyllostomid and human LYZ; compare turbidimetric muramidase rates on Micrococcus lysodeikticus cell walls across pH and NaCl gradients, and determine minimum inhibitory concentrations against Gram-positive and Gram-negative bacteria with and without an outer-membrane permeabiliser. Test individual sanguivore-clade substitutions by site-directed mutagenesis in the frugivorous background.
Hypothesis: Sanguivore-specific substitutions in vampire bat lysozyme alter its antibacterial spectrum or its activity under the ionic conditions of blood.
Type: Recombinant enzymology with site-directed mutagenesis
Experiment: Quantify lysozyme in saliva expectorated by feeding bats by targeted parallel reaction monitoring mass spectrometry, and localise the protein within accessory versus principal submaxillary gland sections by immunohistochemistry.
Hypothesis: Vampire bat lysozyme is secreted into saliva and reaches the host bite site.
Type: Targeted proteomics and immunohistochemistry
Experiment: Measure lysozyme transcript abundance and muramidase activity in stomach and intestinal tissue and contents versus salivary gland, and assay the recombinant enzyme for stability and activity at gastric pH and against pepsin.
Hypothesis: In the absence of a duplicated paralogue, the single vampire bat lysozyme also acts on the ingested blood meal in the digestive tract.
Type: Tissue expression profiling with activity assay
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