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Forward Genetics in Apicomplexa Biology: The Host Side of the Story.

ABSTRACT: Forward genetic approaches have been widely used in parasitology and have proven their power to reveal the complexities of host-parasite interactions in an unbiased fashion. Many aspects of the parasite's biology, including the identification of virulence factors, replication determinants, antibiotic resistance genes, and other factors required for parasitic life, have been discovered using such strategies. Forward genetic approaches have also been employed to understand host resistance mechanisms to parasitic infection. Here, we will introduce and review all forward genetic approaches that have been used to identify host factors involved with Apicomplexa infections, which include classical genetic screens and QTL mapping, GWAS, ENU mutagenesis, overexpression, RNAi and CRISPR-Cas9 library screens. Collectively, these screens have improved our understanding of host resistance mechanisms, immune regulation, vaccine and drug designs for Apicomplexa parasites. We will also discuss how recent advances in molecular genetics give present opportunities to further explore host-parasite relationships.

SUBMITTER: Sanchez-Arcila JC

PROVIDER: S-EPMC9133346 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Forward Genetics in Apicomplexa Biology: The Host Side of the Story.

Sánchez-Arcila Juan C JC Jensen Kirk D C KDC

Frontiers in cellular and infection microbiology 20220512

Forward genetic approaches have been widely used in parasitology and have proven their power to reveal the complexities of host-parasite interactions in an unbiased fashion. Many aspects of the parasite's biology, including the identification of virulence factors, replication determinants, antibiotic resistance genes, and other factors required for parasitic life, have been discovered using such strategies. Forward genetic approaches have also been employed to understand host resistance mechanis ...[more]

PMID: 35646724

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Project description:The fungal wheat pathogen Zymoseptoria tritici possesses a large complement of accessory chromosomes showing presence/absence polymorphism among isolates. These chromosomes encode hundreds of genes; however, their functional role and why the chromosomes have been maintained over long evolutionary times are so far not known. In this study, we addressed the functional relevance of eight accessory chromosomes in reference isolate IPO323. We induced chromosome losses by inhibiting the β-tubulin assembly during mitosis using carbendazim and generated several independent isogenic strains, each lacking one of the accessory chromosomes. We confirmed chromosome losses by electrophoretic karyotyping and whole-genome sequencing. To assess the importance of the individual chromosomes during host infection, we performed in planta assays comparing disease development results in wild-type and chromosome mutant strains. Loss of the accessory chromosomes 14, 16, 18, 19, and 21 resulted in increased virulence on wheat cultivar Runal but not on cultivars Obelisk, Titlis, and Riband. Moreover, some accessory chromosomes affected the switch from biotrophy to necrotrophy as strains lacking accessory chromosomes 14, 18, 19, and 21 showed a significantly earlier onset of necrosis than the wild type on the Runal cultivar. In general, we observed that the timing of the lifestyle switch affects the fitness of Z. tritici Taking the results together, this study was the first to use a forward-genetics approach to demonstrate a cultivar-dependent functional relevance of the accessory chromosomes of Z. tritici during host infection.IMPORTANCEZymoseptoria tritici is a prominent fungal pathogen of wheat of worldwide distribution. This fungus shows a remarkable genome organization, with a large number of chromosomes that are present in only some isolates and therefore considered to be "accessory" chromosomes. To date, the function of these accessory chromosomes in Z. tritici has been unknown, although their maintenance in the species over evolutionary times suggests a functional relevance. Here we deleted whole accessory chromosomes to test the effect of these chromosomes on host specificity and virulence of the fungus. We show for the first time that some accessory chromosomes of Z. tritici affect the fitness of the fungus during host infection in a cultivar-dependent manner. These results show that the accessory chromosomes encode host-specific virulence determinants having a negative effect on fitness. Understanding the population dynamic of the accessory chromosomes and the molecular interaction of pathogen and plant traits is crucial to improve wheat-breeding strategies.

Dataset Information

Forward Genetics in Apicomplexa Biology: The Host Side of the Story.

Publications

Forward Genetics in Apicomplexa Biology: The Host Side of the Story.

Similar Datasets

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