Genetic mechanisms of snail/schistosome compatibility

蜗牛/血吸虫相容性的遗传机制

• 批准号: 10725889
• 负责人: Michael Scott Blouin
• 金额: $ 37.13万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-10 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10725889
• 关键词: Affect; Alleles; Binding; Biomphalaria; Candidate Disease Gene; Chronic; Chronic Disease; Clustered Regularly Interspaced Short Palindromic Repeats; Code; Country; DNA Sequence; Data; Dose; Drug resistance; Etiology; Generations; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genome Scan; Genomic Segment; Geography; Goals; Haplotypes; Helminths; Homozygote; Immune response; Immunology; Inbreeding; Individual; Infection; Interruption; Knock-out; Knowledge; Ligands; Link; Location; Maps; Methods; Modernization; Modification; Molecular; Names; Natural Resistance; Parasites; Parasitic Diseases; Pathway interactions; Persons; Pharmaceutical Preparations; Poison; Population; Predisposition; Quantitative Trait Loci; RNA Interference; Research; Resistance; Resistance to infection; Schistosoma; Schistosoma mansoni; Schistosoma mansonii infection; Schistosomatidae; Schistosomiasis; Side; Snails; Susceptibility Gene; System; Testing; Untranslated RNA; Vaccines; Variant; Work; disability; effective therapy; genetic manipulation; genome wide association study; human disease; novel strategies; public health relevance; resistance gene; resistant strain; snail protein; trait; transcriptome sequencing; transmission blocking; transmission process; waterborne

Schistosomiasis is by far the most important helminth parasitic disease of humans. Vaccines are unavailable, the only effective treatment involves repeated dosing with a single drug, and drug resistance is now a major concern. Schistosomes require aquatic snails for transmission. Mass drug administration alone has proven ineffective at eliminating schistosomiasis. It is now widely accepted that an integrated approach that includes targeting the snail stage is essential. Yet current snail control strategies are unsustainable, involving toxic chemicals or introduced predators or competitors. New approaches are needed to break transmission at the snail stage. Understanding the molecular mechanisms by which snails and schistosomes interact is key for finding new strategies to interrupt transmission. Yet knowledge about molluscan immunology is far from adequate, and decades of painstaking research on the molecular basis of snail-schistosome compatibility have yielded just a handful of candidate genes and mechanisms. BS90 is a highly resistant strain of Biomphalaria glabrata (Bg) that, until recently, was considered completely resistant to all known strains of Schistosoma mansoni (Sm). BS90 has been the subject of many functional studies of why it is so resistant to infection by Sm. So finding the genes behind that trait would be a major advance. We recently determined that two genomic regions we previously discovered using another snail population are involved, and that one or more additional loci still need to be mapped. One strain of Sm can infect some BS90 snails, but there is genetic variation within the outbred BS90 population for susceptibility. In preliminary work we found that a gene in, or linked to, a region we named PTC2 is involved in this resistance polymorphism. The susceptible haplotype appears to act dominantly, suggesting that some molecule on the parasite side must bind to something on the host side to evade the host immune response. Thus, finding the snail protein involved could lead to a key ligand used by schistosomes to defeat the Bg immune response. We will use a combination of GWAS and QTL mapping approaches to narrow down (1) the remaining genomic regions in BS90 snails that make them more resistant to Sm than other populations of snails, and (2) the region/s that control susceptibility to the one strain of Sm that can infect BS90. We will annotate and rank candidate genes within each region (based on predicted function and on sequence or expression difference between haplotypes). Then test candidate genes using RNAi and/or CRISPR knock-out lines. Identifying new resistance genes will substantially advance our knowledge of snail-schistosome immunology. We hope to eventually be able to genetically manipulate natural snail populations to make them less able to transmit schistosomes. Identifying key resistance genes and characterizing their function will be an essential first step toward that goal.

血吸虫病是迄今为止人类最重要的寄生虫病。没有疫苗，

项目成果

PTC2 region genotypes counteract Biomphalaria glabrata population differences between M-line and BS90 in resistance to infection by Schistosoma mansoni.

• DOI: 10.7717/peerj.13971
• 发表时间: 2022
• 期刊: PEERJ
• 影响因子: 2.7
• 作者: Blouin, Michael S.;Bollmann, Stephanie R.;Tennessen, Jacob A.
• 通讯作者: Tennessen, Jacob A.

Heat shock increases hydrogen peroxide release from circulating hemocytes of the snail Biomphalaria glabrata.

• DOI: 10.1016/j.fsi.2020.07.029
• 发表时间: 2020-10
• 期刊: Fish & shellfish immunology
• 影响因子: 4.7
• 作者: Allan ERO;Blouin MS
• 通讯作者: Blouin MS