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Pan-omics-based characterization and prediction of highly multidrugadapted strains from an outbreak fungal species complex

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The Innovation 2024年第5期5卷 101-109,100页

作者： Xin Fan Lei Chen Min Chen Na Zhang Hong Chang Mingjie He Zhenghao Shen Lanyue Zhang Hao Ding Yuyan Xie Yemei Huang Weixin Ke Meng Xiao Xuelei Zang Heping Xu Wenxia Fang Shaojie Li Cunwei Cao Yingchun Xu Shiguang Shan Wenjuan Wu Changbin Chen Xinying Xue Linqi Wang Department of Infectious Diseases and Clinical Microbiology Beijing Institute of Respiratory Medicine and Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China Beijing Research Center for Respiratory Infectious Diseases Beijing 100020China State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Department of Dermatology Shanghai Key Laboratory of Molecular Medical MycologyChangzheng HospitalShanghai 200003China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Intelligent Information Processing Institute of Computing TechnologyChinese Academy of SciencesBeijing 100190China Department of Respiratory and Critical Care Emergency and Critical Care Medical CenterBeijing Shijitan HospitalCapital Medical UniversityBeijing 100038China Department of Laboratory Medicine State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive fungal Diseases Beijing 100730China Department of Clinical Laboratory First Affiliated Hospital of Xiamen UniversityXiamen 361003China Institute of Biological Science and Technology Guangxi Academy of SciencesNanning 530007China Department of Dermatology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Guangxi Key Laboratory of Mycosis Prevention and Treatment Nanning 530021China Department of Laboratory Medicine Shanghai East HospitalTongji University School of MedicineShanghai 200120China the unit of pathogenic fungal infection&host immunity Shanghai Institute of Immunity and InfectionChinese Academy of SciencesShanghai 200031China Nanjing Advanced Academy of Life and Health Nanjing 211135China Department of Respiratory and Critical Care Shandong Second Medical UniversityWeifang 261035China

Strains from the Cryptococcus gattii species complex(CGSC)have caused the Pacific Northwest cryptococcosis outbreak,the largest cluster of lifethreatening fungal infections in otherwise healthy human hosts known to *** this study,we utilized a pan-phenome-based method to assess the fitness outcomes of CGSC strains under 31 stress conditions,providing a comprehensive overview of 2,821 phenotype-strain associations within this pathogenic *** clustering analysis revealed a strong correlation between distinct types of stress phenotypes in a subset of CGSC strains,suggesting that shared determinants coordinate their adaptations to various ***,a specific group of strains,including the outbreak isolates,exhibited a remarkable ability to adapt to all three of the most commonly used antifungal drugs for treating cryptococcosis(amphotericin B,5-fluorocytosine,and fluconazole).By integrating pan-genomic and pan-transcriptomic analyses,we identified previously unrecognized genes that play crucial roles in conferring multidrug resistance in an outbreak strain with high multidrug *** these genes,we identified biomarkers that enable the accurate prediction of highly multidrug-adapted CGSC strains,achieving maximum accuracy and area under the curve(AUC)of 0.79 and 0.86,respectively,using machine learning ***,we developed a pan-omic approach to identify cryptococcal multidrug resistance determinants and predict highly multidrug-adapted CGSC strains that may pose significant clinical concern.

关键词： multidrug adapted prediction

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Mechanisms of how a family of secreted Candida albicans virulence factors modulates host immunity

Mechanisms of how a family of secreted Candida albicans viru...

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第九届中国模式真菌研讨会

作者： Yuanyuan Wang Xiaoqing Chen Xinhua Huang Changbin Chen unit of pathogenic fungal infection & host immunity Institut Pasteur of Shanghai Chinese Academy of Sciences

Candida albicansis an important opportunistic human fungal pathogen,its survival and pathogenicity require expression of different virulence *** these,secreted virulence factors represent one of the key players that p...

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A novel pH adaptation regulator in Candida albicans

A novel pH adaptation regulator in Candida albicans

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多彩菌物美丽中国——中国菌物学会2019年学术年会

作者： Tong Jiang Changbin Chen unit of pathogenic fungal infection ＆ host immunity Institute Pasteur of Shanghai Chinese Academy of Sciences

As an important human conditional pathogenic fungus, Candida albicans’ s ability to sense and adapt to environmental changes is crucial for their survival and reproduction in the host. However, the pH value of different organs varies greatly, and the pH value of the host environment is often in a dynamic process. Therefore,the ability to sense and adapt to the extracellular pH value is the key to the success of symbiosis and pathogenesis of Candida albicans in the host. As an opportunistic pathogen, Candida albicans can perceive different pH of the host environment, especially the alkaline pH, which is an important mechanism for symbiosis to pathogenic transformation. Through preliminary laboratory work, we found a new transcription factor Ppc1 that plays an important regulatory role in the adaptation to alkaline pH. Currently, researches on alkaline pH sensing of Candida albicans mainly focus on conservative Rim101/PacC pathway. By comparing with RIM101 knockout strain, we found that the PPC1 knockout strain is more sensitive to the alkaline pH value. RNA-seq suggested that RIM101 and PPC1 are both involved in the Candida albicans neutral alkaline pH adaptation process and play a key role,but the alkaline-dependent genes regulated by PPC1 and RIM101 are not identical. Quantitatively, PPC1 regulated more alkaline-dependent genes. GO analysis revealed PPC1 and RIM101 regulate similar biological pathways which indicated that Ppc1 is a novel neutral-alkaline pH adaptation regulator in Candida albicans. An in-depth exploration of the interaction mechanism between Ppc1 and Rim101 in the process of regulating the environmental pH adaptation of Candida albicans is of great significance to deepen the understanding of the symbiosis-pathogenic transformation mechanism of Candida albicans and to discover new methods of curing fungal infection.

关键词： Candida albicans pH adaptation RNA-seq

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Assessing risk of Bombali virus spillover to humans by mutagenesis analysis of viral glycoprotein

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hLife 2024年第1期2卷 32-42页

作者： Lincan Li Tianyu Gan Ziyue Ma Yi Huang Jin Zhong unit of Viral Hepatitis CAS Key Laboratory of Molecular Virology and ImmunologyShanghai Institute of Immunity and InfectionCenter for Biosafety Mega-ScienceChinese Academy of SciencesShanghaiChina University of Chinese Academy of Sciences BeijingChina ShanghaiTech University ShanghaiChina Wuhan National Biosafety Laboratory Center for Biosafety Mega-ScienceChinese Academy of SciencesHubeiChina

Ebolaviruses,such as the highly pathogenic Ebola virus(EBOV),belong to the family Filoviridae and have caused out-breaks of severe and fatal hemorrhagic fever over the past *** virus(BOMV)is a newly discovered ebolavirus from bats with unknown potential to infect *** most ebolaviruses,the interaction between viral glycoprotein(GP)and host receptor Niemann-Pick C1(NPC1)is crucial for viral entry and determines host ***,we analyzed the BOMV GP-mediated virus entry into human cells using our recently developed EBOV transcription-and replication-competent virus-like particle(trVLP)*** demonstrated that while BOMV GP can be efﬁciently incorporated into trVLPs,it is inefﬁcient in mediating trVLP entry into human ***,BOMV GP-mediated virus entry into human cells can be signiﬁcantly enhanced by a few mutations in the NPC1-binding domain of ***,we showed that these mutations increase the binding of BOMV-GP to human *** summary,our results suggested that although wild-type BOMV does not efﬁciently infect human cells,the emergence of mutations in viral GP may boost its ability to spill over to humans,highlighting the importance of monitoring BOMV GP evolution in preventing potential BOMV spillover events.

关键词： Bombali virus glycoprotein entry Ebola virus Niemann-Pick C1

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Modulation of intracellular level of the iron-responsive regulator Sefl by a cargo protein Nmd5prevents inappropriate gene activation in the human fungal pathogen Candida albicans

Modulation of intracellular level of the iron-responsive reg...

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第十二届海峡两岸真菌学学术研讨会

作者： Huang,Xin-Hua Noble,Suzanne M. Chen,Chang-Bin unit of pathogenic fungal infection&host immunity Institute Pasteur of ShanghaiChinese Academy of Sciences Department of Microbiology&Immunology University of California-San Francisco

pathogenic fungi,like bacterial pathogens,must capture iron from host tissues and regulate iron homeostasis to avoid *** the opportunistic human fungal pathogen Candida albicans,we previously discovered that a ZnCys zinc knuckle transcriptional factor Sefl,acts to regulate iron homeostasis by integrating into a highly conserved regulatory circuit with reciprocal roles in C.

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Gut microbiota-derived metabolites as key mucosal barrier modulators in obesity

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World Journal of Gastroenterology 2021年第33期27卷 5555-5565页

作者： Yan-Xia Wei Kui-Yang Zheng Yu-Gang Wang Laboratory of infection and immunity Jiangsu Key Laboratory of Immunity and MetabolismDepartment of Pathogenic Biology and ImmunologyXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina

A significant breakthrough in the field of obesity research was the demonstration that an obese phenotype could be manipulated by modulating the gut *** important next step is to elucidate a human-relevant"map"of microbiota-host interactions that regulate the metabolic health of the *** improved understanding of this crosstalk is a prerequisite for optimizing therapeutic strategies to combat *** mucosal barrier dysfunction is an important contributor to metabolic diseases and has also been found to be involved in a variety of other chronic inflammatory conditions,including cancer,neurodegeneration,and *** mechanistic basis for intestinal barrier dysfunction accompanying metabolic disorders remains poorly *** the molecular and cellular modulators of intestinal barrier function will help devise improved strategies to counteract the detrimental systemic consequences of gut barrier *** in the composition and function of the gut microbiota,i.e.,dysbiosis,are thought to drive obesity-related pathogenesis and may be one of the most important drivers of mucosal barrier *** effects of the microbiota on the host are mediated by microbiota-derived *** this review,we focus on several relatively well-studied microbial metabolites that can influence intestinal mucosal homeostasis and discuss how they might affect metabolic *** design and use of microbes and their metabolites that are locally active in the gut without systemic side effects are promising novel and safe therapeutic modalities for metabolic diseases.

关键词： Obesity Metabolic diseases Microbiota Mucosal homeostasis Gut Microbial metabolites

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Genetic diversity and phylogenetic analysis of EG95 sequences of Echinococcus granulosus:Implications for EG95 vaccine application

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Asian Pacific Journal of Tropical Medicine 2017年第5期10卷 497-500页

作者： Wei Pan De-Sheng Chen Yun-Juan Lu Hui-Wen Xu Wen-Ting Hao Ya-Wen Zhang Su-Ping Qin Kui-Yang Zheng Ren-Xian Tang Jiangsu Key Laboratory of immunity and Metabolism Department of Pathogenic Biology and ImmunologyLaboratory of Infection and ImmunityXuzhou Medical University Department of Clinical Medicine Xuzhou Medical University

Objective:To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus(E. granulosus). Methods:We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1(DNASTAR Inc.,Madison,WI),and the phylogenetic analysis was performed by using MEGA5.1(CEMI,Tempe,AZ,USA). In addition,linear and conformational epitopes were analysed,including secondary structure,NXT/S glycosylation,fibronectin type ecoⅢ(Fnndary Ⅲ) domain and glycosylphosphatidylinositol anchor signal(GPIanchor). The s structure was predicted by PSIPRED method. Results:Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence,X90928. However,EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates,respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine,X90928,and they belonged to Subgroup 1. However,in comparison to X90928,several amino acid mutations occurred in most isolates besides oncosphere,which potentially altered the immunodominant linear epitopes,glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. Conclusions:This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates,and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.

关键词： Echinococcus granulosus Cystic echinococcosis EG95 Vaccine Genetic diversity

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Antifungal Activities and Attenuating In Vitro MAP4K3 Kinase Activities of Poria Polysaccharide Extracts

Antifungal Activities and Attenuating In Vitro MAP4K3 Kinase...

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中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者：洪涛刘微王福玲贾琦高原陈昌斌 School of Pharmacy Harbin University of Commerce The Centre for Life Sciences and Environmental Sciences Harbin University of Commerce Institute of Cell and Molecular Biology Harbin University of Commerce unit of pathogenic fungal infection and host immunity InstitutP asteur of Shanghai Chinese Academy of Science

Poria extracts used in traditional Chinese medicine have widely physiological effects includingcontributing to improving the immunity of the organism. The polysaccharide is animportant active ingredient in Poria extracts. We have previously shown that MAP4K3 is acomponent on the amino acid-sensitive signaling pathway to mTOR. Moreover, MAP4K3 kinase links signal transduction from SLP-76 to PKC-θ in the TCR signaling cascade andcould be used as new diagnostic biomarkers and therapeutic targets for autoimmunity ***, we report that Pior polysaccharide extracts have gotten by using water extractionmethod and alkaline extraction method. Further we also purify the *** results show that the acid polysaccharide extracts can inhibit the growth of CandidaAlbicans and its MIC is 12.5mg/mL, and neutral polysaccharide extracts can significantly attenuatewild type and its mutant MAP4K3 kinase activity in vitro. This study provides somebasis data and useful method for the subsequent in vivo experiments.

关键词： Antifungal Activities MAP4K3 Poria Polysaccharides Isolation and Purification

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E）NA sensor cGAS-mediated immune recognition

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Protein & Cell 2016年第11期7卷 777-791页

作者： Pengyan Xia Shuo Wang Pu Gao Guangxia Gao Zusen Fan Key Laboratory of infection and immunity of CAS CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049China

The host takes use of pattern recognition receptors （PRRs） to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. pathogenic DNAs are supposed to be detected by DNA sensors that induce the activation of NFKB or TBKI-IRF3 pathway. DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types, cGAS binds to DNA, followed by a conformational change that allows the synthesis of cyclic guanosine monophosphate-adenosine monophosphate （cGAMP） from adenosine triphosphate and guanosine triphos- phate, cGAMP is a strong activator of STING that can activate IRF3 and subsequent type I interferon produc- tion. Here we describe recent progresses in DNA sensors especially cGAS in the innate immune responses against pathogenic DNAs.

关键词： cGAS cGAMP innate immunity cytosolic DNAs DNA sensors

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Peroxisome Dynamics Determines host-derived ROS Accumulation and Infectious Growth of the Rice Blast Fungus

Peroxisome Dynamics Determines Host-derived ROS Accumulation...

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中国植物病理学会2024年学术年会

作者：张俊 LI Huimin GU Wangliu ZHANG Kexin LIU Xinyu LIU Muxing YANG Leiyun LI Gang ZHANG Zhengguang 张海峰 Department of Plant Pathology College of Plant ProtectionNanjing Agricultural Universityand Key Laboratory of Integrated Management of Crop Diseases and PestsMinistry of Education The Key Laboratory of Plant immunity Nanjing Agricultural University

During the early stages of host-pathogen interaction,the production of reactive oxygen species(ROS) in host cells is a critical strategy to halt the spread of *** have to minimize the deleterious effects of host-generated ROS for successful ***,the underlying mechanism remains largely ***,we report that a peroxisomal 3-ketoacyl-CoA thiolase of rice blast fungus ***,MoKat2,functions in host ROS homeostasis likely through regulating fungal peroxisome morphology during *** peroxisome elongates in response to ROS stress and this is attributed to the function of peroxisome localized ***2 forms homodimer in vivo while the homodimer is dissociated into monomer in response to host-derived *** MoKat2 monomer binds to peroxisome membranes through its amphipathic helices to control peroxisome elongation,resulting in host ROS depletion and subsequent *** invasion in rice *** findings shed light on the interplay between pathogenic peroxisome dynamics and host ROS accumulation,expanding the crucial role of organelle-mediated infection in plant-microbe interactions.

关键词： M. oryzae-rice interaction peroxisome dynamics host-derived ROS MoKat2 infectious growth

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