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Pseudomonas aeruginosa core metabolism exerts a widespread growth-independent control on virulence

ABSTRACT: Gene expression analysis of highly vs. lowly pathogenic P. aeruginosa strains identifies many virulence factors and only a few metabolism genes related to virulence. Functional transcriptomics re-analysis of core metabolism at the pathway level, reveals amino-acid, succinate, citramalate, and chorismate biosynthesis and beta-oxidation as important for full virulence and expression of these pathways indicative of virulence in various strains.

ORGANISM(S): Pseudomonas aeruginosa

PROVIDER: GSE142464 | GEO | 2020/01/02

REPOSITORIES: GEO

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Project description:Background: Studying genomic variation in rapidly evolving pathogens potentially enables definition of genes supporting their “core biology” present, functional and expressed by all strains or “flexible biology”, varying between strains. Genes supporting flexible biology may be considered to be “accessory”, whilst the “core” gene set is likely to be important for common features of a pathogen species biology, including virulence on all host genotypes. The wheat-pathogenic fungus Zymoseptoria tritici represents one of the most rapidly evolving threats to global food security and was the focus of this study. Results:We constructed a pangenome of 18 European field isolates, with 12 also subjected to RNAseq transcription profiling during infection. Combining this data, we predicted a “core” gene set comprising 9807 sequences which were; (1) present in all isolates; (2) lacking inactivating polymorphisms ; and (3) expressed by all isolates. A large accessory genome, consisting of 45% of the total genes was also defined. We classified genetic and genomic polymorphism at both chromosomal and individual gene scales. Proteins required for essential functions including virulence, had lower-than average sequence variability amongst core genes. Both core and accessory genomes encoded many small, secreted candidate effector proteins that likely interact with plant immunity. Viral vector-mediated transient in planta overexpression of 88 candidates failed to identify any which induced leaf necrosis characteristic of disease. However, functional complementation of a non-pathogenic deletion mutant lacking five core genes, demonstrated that full virulence was restored by re-introduction of the single gene exhibiting least sequence polymorphism and highest expression. Conclusions:These data support the combined use of pangenomics and transcriptomics for defining genes which represent core, and potentially exploitable, weaknesses in rapidly evolving pathogens.

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Pseudomonas aeruginosa core metabolism exerts a widespread growth-independent control on virulence

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