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host pathogen interactions in Helicobacter pylori related gastric cancer

World Journal of Gastroenterology 2017年第9期23卷 1521-1540页

作者： Magdalena Chmiela Zuzanna Karwowska Weronika Gonciarz Bujana Allushi Pawel Staczek Department of Immunology and Infectious Biology Institute of MicrobiologyBiotechnology and ImmunologyFaculty of Biology and Environmental ProtectionUniversity of Lodz Department of Genetics of Bacteria Institute of MicrobiologyBiotechnology and ImmunologyFaculty of Biology and Environmental ProtectionUniversity of Lodz

Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world’s population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.

关键词： Helicobacter pylori host susceptibility Carcinogenesis Bacterial diversity

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Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq approach

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Animal Models and Experimental Medicine 2024年第1期7卷 36-47页

作者： Roa'a H.S.Yosief Iqbal M.Lone Aharon Nachshon Heinz Himmelbauer Irit Gat-Viks Fuad A.Iraqi Department of Clinical Microbiology and Immunology Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael School of Molecular Cell Biology and Biotechnology George S.Wise Faculty of Life SciencesTel Aviv UniversityTel AvivIsrael Institute of Computational Biology Department of BiotechnologyUniversity of Natural Resources and Life SciencesMuthgasse 181190 ViennaAustria

Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic *** aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene ***:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with *** tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was *** GENE-E analysis platform was used to generate a clustered heat map ***:Significant variation in body weight changes between CC lines was *** gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight ***,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome ***:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards *** a next step,eQTL analysis will be performed for our RNA-Seq *** candidate genes from our study will be further assessed with a human cohort with aspergillosis.

关键词： aspergillus fumigatus infection collaborative cross(CC)mice gene expression profile gene-network host susceptibility quantitative trait loci(QTL)mapping RNA-Seq

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The Rhinolophus affinis bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2

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Science Bulletin 2021年第12期66卷 1215-1227,M0004页

作者： Pei Li Ruixuan Guo Yan Liu Yingtao Zhang Jiaxin Hu Xiuyuan Ou Dan Mi Ting Chen Zhixia Mu Yelin Han Zihan Chen Zhewei Cui Leiliang Zhang Xinquan Wang Zhiqiang Wu Jianwei Wang Qi Jin Zhaohui Qian NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100176China School of Pharmaceutical Sciences Peking UniversityBeijing 100191China Institute of Basic Medicine Shandong First Medical University&Shandong Academy of Medical SciencesJinan 250062China The Ministry of Education Key Laboratory of Protein Science Beijing Advanced Innovation Center for Structural BiologyBeijing Frontier Research Center for Biological StructureCollaborative Innovation Center for BiotherapySchool of Life SciencesTsinghua UniversityBeijing 100084China

Bat coronavirus(CoV)RaTG13 shares the highest genome sequence identity with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)among all known coronaviruses,and also uses human angiotensin converting enzyme 2(hACE2)for virus ***,SARS-CoV-2 is thought to have originated from ***,whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains ***,we found that Rhinolophus affinis bat ACE2(Ra ACE2)is an entry receptor for both SARSCoV-2 and Ra TG13,although the binding of Ra ACE2 to the receptor-binding domain(RBD)of SARSCoV-2 is markedly weaker than that of h *** further evaluated the receptor activities of ACE2 s from additional 16 diverse animal species for Ra TG13,SARS-CoV,and SARS-CoV-2 in terms of S protein binding,membrane fusion,and pseudovirus *** found that the Ra TG13 spike(S)protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2,and seven out of sixteen different ACE2 s function as entry receptors for all three viruses,indicating that all three viruses might have broad host *** note,Ra TG13 S pseudovirions can use mouse,but not pangolin ACE2,for virus entry,whereas SARS-CoV-2 S pseudovirions can use pangolin,but not mouse,ACE2 enter cells *** analysis revealed that residues 484 and 498 in Ra TG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2 ***,two polymorphous Rhinolophous sinicus bat ACE2 s showed different susceptibilities to virus entry by Ra TG13 and SARS-CoV-2 S pseudovirions,suggesting possible *** results offer better understanding of the mechanism of coronavirus entry,host range,and virushost coevolution.

关键词： SARS-CoV-2 Bat coronavirus RaTG13 Spike protein Rhinolophus affinis bat ACE2 host susceptibility Coronavirus entry

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