Zhendong Du , Danni Tong , Xueqiu Chen , Fei Wu , Shengjun Jiang , Jingju Zhang , Yi Yang , Rui Wang , Sambuu Gantuya , Tserennyam Davaajargal , Sukhbaatar Lkhagvatseren , Zayat Batsukh , Aifang Du , Guangxu Ma
{"title":"对理发杆蠕虫 nhr 基因家族进行全基因组 RNA 干扰,发现了对幼虫体外存活至关重要的成员。","authors":"Zhendong Du , Danni Tong , Xueqiu Chen , Fei Wu , Shengjun Jiang , Jingju Zhang , Yi Yang , Rui Wang , Sambuu Gantuya , Tserennyam Davaajargal , Sukhbaatar Lkhagvatseren , Zayat Batsukh , Aifang Du , Guangxu Ma","doi":"10.1016/j.meegid.2024.105609","DOIUrl":null,"url":null,"abstract":"<div><p>Nuclear hormone receptors (NHRs) are emerging target candidates against nematode infection and resistance. However, there is a lack of comprehensive information on NHR-coding genes in parasitic nematodes. In this study, we curated the <em>nhr</em> gene family for 60 major parasitic nematodes from humans and animals. Compared with the free-living model organism <em>Caenorhabditis elegans</em>, a remarkable contraction of the <em>nhr</em> family was revealed in parasitic species, with genetic diversification and conservation unveiled among nematode Clades I (10–13), III (16–42), IV (33–35) and V (25–64). Using an <em>in vitro</em> biosystem, we demonstrated that 40 <em>nhr</em> genes in a blood-feeding nematode <em>Haemonchus contortus</em> (clade V; barber's pole worm) were responsive to host serum and one <em>nhr</em> gene (<em>i.e.</em>, <em>nhr-64</em>) was consistently stimulated by anthelmintics (<em>i.e.</em>, ivermectin, thiabendazole and levamisole); Using a high-throughput RNA interference platform, we knocked down 43 <em>nhr</em> genes of <em>H. contortus</em> and identified at least two genes that are required for the viability (<em>i.e.</em>, <em>nhr-105</em>) and development (<em>i.e.</em>, <em>nhr-17</em>) of the infective larvae of this parasitic nematode <em>in vitro</em>. Harnessing this preliminary functional atlas of <em>nhr</em> genes for <em>H. contortus</em> will prime the biological studies of this gene family in nematode genetics, infection, and anthelmintic metabolism within host animals, as well as the promising discovery of novel intervention targets.</p></div>","PeriodicalId":54986,"journal":{"name":"Infection Genetics and Evolution","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567134824000601/pdfft?md5=be2180ce9b1468c271d64c55af3ff979&pid=1-s2.0-S1567134824000601-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Genome-wide RNA interference of the nhr gene family in barber's pole worm identified members crucial for larval viability in vitro\",\"authors\":\"Zhendong Du , Danni Tong , Xueqiu Chen , Fei Wu , Shengjun Jiang , Jingju Zhang , Yi Yang , Rui Wang , Sambuu Gantuya , Tserennyam Davaajargal , Sukhbaatar Lkhagvatseren , Zayat Batsukh , Aifang Du , Guangxu Ma\",\"doi\":\"10.1016/j.meegid.2024.105609\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Nuclear hormone receptors (NHRs) are emerging target candidates against nematode infection and resistance. However, there is a lack of comprehensive information on NHR-coding genes in parasitic nematodes. In this study, we curated the <em>nhr</em> gene family for 60 major parasitic nematodes from humans and animals. Compared with the free-living model organism <em>Caenorhabditis elegans</em>, a remarkable contraction of the <em>nhr</em> family was revealed in parasitic species, with genetic diversification and conservation unveiled among nematode Clades I (10–13), III (16–42), IV (33–35) and V (25–64). Using an <em>in vitro</em> biosystem, we demonstrated that 40 <em>nhr</em> genes in a blood-feeding nematode <em>Haemonchus contortus</em> (clade V; barber's pole worm) were responsive to host serum and one <em>nhr</em> gene (<em>i.e.</em>, <em>nhr-64</em>) was consistently stimulated by anthelmintics (<em>i.e.</em>, ivermectin, thiabendazole and levamisole); Using a high-throughput RNA interference platform, we knocked down 43 <em>nhr</em> genes of <em>H. contortus</em> and identified at least two genes that are required for the viability (<em>i.e.</em>, <em>nhr-105</em>) and development (<em>i.e.</em>, <em>nhr-17</em>) of the infective larvae of this parasitic nematode <em>in vitro</em>. 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Genome-wide RNA interference of the nhr gene family in barber's pole worm identified members crucial for larval viability in vitro
Nuclear hormone receptors (NHRs) are emerging target candidates against nematode infection and resistance. However, there is a lack of comprehensive information on NHR-coding genes in parasitic nematodes. In this study, we curated the nhr gene family for 60 major parasitic nematodes from humans and animals. Compared with the free-living model organism Caenorhabditis elegans, a remarkable contraction of the nhr family was revealed in parasitic species, with genetic diversification and conservation unveiled among nematode Clades I (10–13), III (16–42), IV (33–35) and V (25–64). Using an in vitro biosystem, we demonstrated that 40 nhr genes in a blood-feeding nematode Haemonchus contortus (clade V; barber's pole worm) were responsive to host serum and one nhr gene (i.e., nhr-64) was consistently stimulated by anthelmintics (i.e., ivermectin, thiabendazole and levamisole); Using a high-throughput RNA interference platform, we knocked down 43 nhr genes of H. contortus and identified at least two genes that are required for the viability (i.e., nhr-105) and development (i.e., nhr-17) of the infective larvae of this parasitic nematode in vitro. Harnessing this preliminary functional atlas of nhr genes for H. contortus will prime the biological studies of this gene family in nematode genetics, infection, and anthelmintic metabolism within host animals, as well as the promising discovery of novel intervention targets.
期刊介绍:
(aka Journal of Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases -- MEEGID)
Infectious diseases constitute one of the main challenges to medical science in the coming century. The impressive development of molecular megatechnologies and of bioinformatics have greatly increased our knowledge of the evolution, transmission and pathogenicity of infectious diseases. Research has shown that host susceptibility to many infectious diseases has a genetic basis. Furthermore, much is now known on the molecular epidemiology, evolution and virulence of pathogenic agents, as well as their resistance to drugs, vaccines, and antibiotics. Equally, research on the genetics of disease vectors has greatly improved our understanding of their systematics, has increased our capacity to identify target populations for control or intervention, and has provided detailed information on the mechanisms of insecticide resistance.
However, the genetics and evolutionary biology of hosts, pathogens and vectors have tended to develop as three separate fields of research. This artificial compartmentalisation is of concern due to our growing appreciation of the strong co-evolutionary interactions among hosts, pathogens and vectors.
Infection, Genetics and Evolution and its companion congress [MEEGID](http://www.meegidconference.com/) (for Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases) are the main forum acting for the cross-fertilization between evolutionary science and biomedical research on infectious diseases.
Infection, Genetics and Evolution is the only journal that welcomes articles dealing with the genetics and evolutionary biology of hosts, pathogens and vectors, and coevolution processes among them in relation to infection and disease manifestation. All infectious models enter the scope of the journal, including pathogens of humans, animals and plants, either parasites, fungi, bacteria, viruses or prions. The journal welcomes articles dealing with genetics, population genetics, genomics, postgenomics, gene expression, evolutionary biology, population dynamics, mathematical modeling and bioinformatics. We also provide many author benefits, such as free PDFs, a liberal copyright policy, special discounts on Elsevier publications and much more. Please click here for more information on our author services .