In vivo competitive fitness profiling reveals protein kinases required for adaptation of Aspergillus fumigatus to the murine host environment

Author:

Can Zhao, Najes Alfuraiji, Hajer Alshraim, Elaine Bignell, Michael Bromley

Author address:

Manchester Fungal Infection Group, University of Manchester, Manchester, UK

Full conference title:

15th European Conference on Fungal Genetics 2020

Date: 20 June 2020

Abstract:

Our understandings of the factors that drive pathogenicity in Aspergillus fumigatus are limited. In this study we provide a functional genomic analysis to describe the role of protein kinases in the pathobiology of A. fumigatus.

As part of the A. fumigatus genome-wide knockout program, we have generated a library of 90 genetically barcoded protein kinase null mutants. Using a competitive fitness profiling approach, we assessed the relative fitness of each mutant under 10 in vitro growth conditions, and in two host models (Galleria mellonella larvae and neutropenic mouse). By comparing the null mutants using their fitness scores, clusters of kinases from known signalling pathways were identified alongside other clusters of kinases that may represent functional partners. Although several mutants had fitness defects in in vitro this did not always correlate with loss of virulence and vice versa, indicating that some kinases are specifically required for adaptation to the host environment.

Link to conference website:

Link Conference abstract: 

ECFG 15

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