Fungal proteins with anti-bacterial properties secreted during infection.

Silke Machata1 , Roland Lehmann2 , Hortense Slevogt2 , Axel Brakhage3 , Ilse Jacobsen1,4

Author address: 

1) Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology- Hans Knöll Institute, Jena, Germany; 2) Septomics Research Center, Jena University Hospital, Jena, Germany; 3) Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology- Hans Knöll Institute, Jena, Germany; 4) Friedrich-Schiller-University, Jena, Germany.

Abstract: 

Aspergillus fumigatus is a saprophytic mold that is responsible for various severe pulmonary fungal diseases including invasive aspergillosis (IA). Various studies have focused their efforts on finding fungal secreted antigens to identify novel biomarkers and vaccine candidates using human patient serum against fungal protein extracts. However, these attempts are limited to the detection of fungal antigens that are produced in liquid growth media and are not suitable for the identification of proteins that are induced only during infection. In the present study, we took advantage of a mouse infection model for IA to analyze the secretome of A. fumigatus in vivo by mass spectrometry allowing the detection of infection-specific fungal proteins in bronchoalveolar lavage samples. Among the ten most abundant secreted fungal proteins were three proteins that have not been previously described and share motifs commonly known in bacteria. They contain NlpC/p60 domains and/or bacterial SH3 domains that are often found in bacterial murein peptidases. Recombinant His-fusion proteins were generated for two of the proteins and their lytic activity was determined against Gram positive and Gram negative bacteria. We found that both proteins are able to cleave Gram positive peptidoglycan with distinct substrate specificity. For at least one of the proteins we also demonstrate bacteriolytic activity against various Gram positive bacteria. The regulatory factors leading to protein expression and secretion still remain to be elucidated. The proteins characterized in this study are not commonly produced under in vitro conditions. However, hypoxia seems to play a role for the induction of gene expression of two of the proteins. Furthermore, the role of common transcriptional regulators in the expression of these proteins is currently investigated by analyzing various A. fumigatus mutant strains. Our current study presents a new group of proteins of A. fumigatus with anti-bacterial activity. While the production of secondary metabolites in Aspergillus acting against the host and other organisms has been investigated in great detail, there have been no descriptions on fungal proteins acting against bacteria. The detailed analysis of newly generated fungal mutants overexpressing our genes of interest will help us to further understand the biological role of these proteins for the lifestyle of A. fumigatus and its interaction with bacteria in microbial communities

2019

abstract No: 

19

Full conference title: 

30th Fungal Genetics Conference 2019
    • Fungal Genetics Conference 30th (2019)