MYCOLab Ai Logo - gold and army green

Identification of a fungal antibacterial endopeptidase that cleaves peptidoglycan

Summary

Scientists discovered a new antibacterial protein called CwhA produced by the fungus Aspergillus fumigatus that acts like molecular scissors, cutting apart the cell walls of harmful bacteria like Staphylococcus aureus. This protein is produced by the fungus when it encounters bacteria in the lungs during infection and helps the fungus fight off bacterial competitors. When CwhA cuts up bacterial cell walls, it creates fragments that alert the immune system, potentially boosting the body’s defense response against infection.

Background

Aspergillus fumigatus is a saprophytic fungus that inhabits soil and decaying plant material alongside bacteria, requiring competitive mechanisms for survival. Previous proteomic analysis of infected mouse lungs identified highly abundant fungal proteins with potential cell wall hydrolase activity. The discovery of antimicrobial proteins in fungi may elucidate fungal-bacterial interactions in both environmental and pathogenic contexts.

Objective

To characterize the previously unidentified fungal protein B0YAY0 and determine its role in bacterial peptidoglycan degradation. The study aimed to understand the conditions inducing CwhA expression and its functional activity against various bacterial species.

Results

CwhA is a secreted endopeptidase containing NlpC/p60 and SH3 domains that cleaves peptidoglycan between amino acids 2 and 3 of the stem peptide in Gram-positive bacteria containing L-lysine. Expression of cwhA is induced by contact with living Gram-positive bacteria and during lung infection. CwhA treatment reduces Staphylococcus aureus viability by 30-50% and leads to bacterial lysis, with resulting peptidoglycan cleavage products stimulating TNF-α and IL-1β production in human immune cells.

Conclusion

CwhA represents the first characterized secreted antibacterial protein in A. fumigatus, functioning as a peptidoglycan-degrading endopeptidase that enables the fungus to suppress Gram-positive bacterial competitors in its environment. The protein’s abundant production in infected lungs and immune stimulatory properties suggest it may modulate both bacterial-fungal interactions and host immune responses during aspergillosis.
  • Published in:EMBO Reports,
  • Study Type:Basic Research,
  • Source: PMID: 40615579, DOI: 10.1038/s44319-025-00508-3
Scroll to Top