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Published on: December 30, 2016
Identification of a fungal antibacterial endopeptidase that cleaves peptidoglycan
Silke Machata1, Ute Bertsche2, Franziska Hoffmann3
1Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute, Jena, Germany.
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.
Insights
Scientists discovered a fungal enzyme, CwhA, secreted by Aspergillus fumigatus. This enzyme targets and lyses Gram-positive bacteria, potentially impacting fungal infections and immune responses.
Area of Science:
- Mycology
- Microbiology
- Immunology
Background:
- Aspergillus fumigatus is a common fungus found in soil and decaying matter.
- It can cause opportunistic infections in immunocompromised individuals.
- Fungal-bacterial interactions are crucial in various environments and infections.
Purpose of the Study:
- To identify secreted antibacterial proteins in Aspergillus fumigatus.
- To characterize the function and impact of a novel fungal endopeptidase, CwhA.
- To investigate the role of CwhA in fungal-bacterial competition and host immune response.
Main Methods:
- Identification and characterization of a secreted fungal endopeptidase (CwhA).
- Analysis of CwhA's peptidoglycan cleavage activity against Gram-positive bacteria.
- Assessment of cwhA gene expression in response to bacterial presence.
- Evaluation of CwhA abundance in infected murine lungs.
- In vitro testing of peptidoglycan cleavage products on human immune cells.
Main Results:
- Discovery of CwhA, a secreted fungal endopeptidase from A. fumigatus.
- CwhA cleaves peptidoglycan in Gram-positive bacteria, leading to cell lysis.
- cwhA expression is induced by bacterial presence.
- CwhA is abundant in murine lungs during invasive pulmonary aspergillosis.
- CwhA-generated peptidoglycan fragments stimulate cytokine production in human immune cells.
Conclusions:
- CwhA is the first identified secreted antibacterial protein in A. fumigatus.
- This enzyme plays a role in fungal-bacterial interactions by inhibiting Gram-positive bacteria.
- CwhA and its cleavage products may modulate the host immune system during infection.
