000K utf8 1100 2025$c2025-08-07 1500 eng 2050 urn:nbn:de:gbv:27-dbt-68023-6 2051 10.1038/s44319-025-00508-3 3000 Machata, Silke 3010 Bertsche, Ute 3010 Brakhage, Axel A 3010 Fattal, Zaher M 3010 Flak, Michal 3010 Hillmann, Falk 3010 Hoffmann, Franziska 3010 Iliou, Alexander N J 3010 Jacobsen, Ilse D 3010 Kage, Franziska 3010 Slevogt, Hortense 3010 von Eggeling, Ferdinand 4000 Identification of a fungal antibacterial endopeptidase that cleaves peptidoglycan [Machata, Silke] 4060 28 Seiten 4209 Abstract Aspergillus fumigatus is a saprophytic fungus dwelling in soil and on decaying plant material, but also an opportunistic pathogen in immunocompromised patients. In its environmental niche, A. fumigatus faces competition from other microorganisms including bacteria. Here, we describe the discovery of the first secreted antibacterial protein in A. fumigatus . We identify a secreted fungal endopeptidase, designated CwhA, that cleaves peptidoglycan of Gram-positive bacteria at specific residues within the peptidoglycan stem peptide. Cleavage leads to bacterial lysis and the release of peptidoglycan cleavage products. Expression of cwhA is induced by the presence of bacteria. Furthermore, CwhA is highly abundant in murine lungs during invasive pulmonary aspergillosis and peptidoglycan cleavage products generated by CwhA stimulate cytokine production of human immune cells in vitro. Although CwhA does not affect human cells directly, this novel player in fungal-bacterial interactions could affect A. fumigatus infections by inhibiting Gram-positive bacteria in its vicinity, and possibly modulate the immune system. 4209 CwhA, a secreted endopeptidase from Aspergillus fumigatus , targets bacterial peptidoglycan and lyses Gram-positive bacteria. Induced within the lung and by bacterial contact, CwhA may enable A. fumigatus to shape its microbial environment. 4209 Synopsis CwhA, a secreted endopeptidase from Aspergillus fumigatus , targets bacterial peptidoglycan and lyses Gram-positive bacteria. Induced within the lung and by bacterial contact, CwhA may enable A. fumigatus to shape its microbial environment. Aspergillus fumigatus expresses CwhA inside the host and upon contact with bacteria, but not in liquid culture. CwhA is an endopeptidase cleaving peptidoglycan of Gram-positive bacteria with L-lysine at position 3 of the stem peptide. CwhA is not toxic to amoeba, host cells and fungal cells but can lead to lysis of Gram-positive bacteria. Peptidoglycan cleavage products can be recognized by the host and lead to cytokine production of TNFα and IL-1β. 4950 https://doi.org/10.1038/s44319-025-00508-3$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:gbv:27-dbt-68023-6$xR$3Volltext$534 4961 https://www.db-thueringen.de/receive/dbt_mods_00068023 5051 570 5550 Aspergillus fumigatus 5550 Cell Wall 5550 Fungal–Bacterial Interactions 5550 Staphylococcus aureus