mLife Pub Date : 2023-06-01 DOI: 10.1002/mlf2.12063

Kun Meng, Jin Yang, Juan Xue, Jun Lv, Ping Zhu, Liuliu Shi, Shan Li

{"title":"A host E3 ubiquitin ligase regulates Salmonella virulence by targeting an SPI‐2 effector involved in SIF biogenesis","authors":"Kun Meng, Jin Yang, Juan Xue, Jun Lv, Ping Zhu, Liuliu Shi, Shan Li","doi":"10.1002/mlf2.12063","DOIUrl":"https://doi.org/10.1002/mlf2.12063","url":null,"abstract":"Abstract Salmonella Typhimurium creates an intracellular niche for its replication by utilizing a large cohort of effectors, including several that function to interfere with host ubiquitin signaling. Although the mechanism of action of many such effectors has been elucidated, how the interplay between the host ubiquitin network and bacterial virulence factors dictates the outcome of infection largely remains undefined. In this study, we found that the SPI‐2 effector SseK3 inhibits SNARE pairing to promote the formation of a Salmonella ‐induced filament by Arg‐GlcNAcylation of SNARE proteins, including SNAP25, VAMP8, and Syntaxin. Further study reveals that host cells counteract the activity of SseK3 by inducing the expression of the E3 ubiquitin ligase TRIM32, which catalyzes K48‐linked ubiquitination on SseK3 and targets its membrane‐associated portion for degradation. Hence, TRIM32 antagonizes SNAP25 Arg‐GlcNAcylation induced by SseK3 to restrict Salmonella ‐induced filament biogenesis and Salmonella replication. Our study reveals a mechanism by which host cells inhibit bacterial replication by eliminating specific virulence factors.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136108096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The archaeal KEOPS complex possesses a functional Gon7 homolog and has an essential function independent of the cellular t⁶A modification level 古细菌KEOPS复合物具有功能性的Gon7同源物，并且具有独立于细胞t6A修饰水平的基本功能

mLife Pub Date : 2023-01-08 DOI: 10.1002/mlf2.12051

Pengju Wu, Qi Gan, Xuemei Zhang, Yunfeng Yang, Yuanxi Xiao, Qunxin She, Jinfeng Ni, Qihong Huang, Yulong Shen

{"title":"The archaeal KEOPS complex possesses a functional Gon7 homolog and has an essential function independent of the cellular t6A modification level","authors":"Pengju Wu, Qi Gan, Xuemei Zhang, Yunfeng Yang, Yuanxi Xiao, Qunxin She, Jinfeng Ni, Qihong Huang, Yulong Shen","doi":"10.1002/mlf2.12051","DOIUrl":"https://doi.org/10.1002/mlf2.12051","url":null,"abstract":"Abstract Kinase, putative Endopeptidase, and Other Proteins of Small size (KEOPS) is a multisubunit protein complex conserved in eukaryotes and archaea. It is composed of Pcc1, Kae1, Bud32, Cgi121, and Gon7 in eukaryotes and is primarily involved in N 6 ‐threonylcarbamoyl adenosine (t 6 A) modification of transfer RNAs (tRNAs). Recently, it was reported that KEOPS participates in homologous recombination (HR) repair in yeast. To characterize the KEOPS in archaea (aKEOPS), we conducted genetic and biochemical analyses of its encoding genes in the hyperthermophilic archaeon Saccharolobus islandicus . We show that aKEOPS also possesses five subunits, Pcc1, Kae1, Bud32, Cgi121, and Pcc1‐like (or Gon7‐like), just like eukaryotic KEOPS. Pcc1‐like has physical interactions with Kae1 and Pcc1 and can mediate the monomerization of the dimeric subcomplex (Kae1‐Pcc1‐Pcc1‐Kae1), suggesting that Pcc1‐like is a functional homolog of the eukaryotic Gon7 subunit. Strikingly, none of the genes encoding aKEOPS subunits, including Pcc1 and Pcc1‐like, can be deleted in the wild type and in a t 6 A modification complementary strain named TsaKI, implying that the aKEOPS complex is essential for an additional cellular process in this archaeon. Knock‐down of the Cgi121 subunit leads to severe growth retardance in the wild type that is partially rescued in TsaKI. These results suggest that aKEOPS plays an essential role independent of the cellular t 6 A modification level. In addition, archaeal Cgi121 possesses dsDNA‐binding activity that relies on its tRNA 3ʹ CCA tail binding module. Our study clarifies the subunit organization of archaeal KEOPS and suggests an origin of eukaryotic Gon7. The study also reveals a possible link between the function in t 6 A modification and the additional function, presumably HR.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135107313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Inspiration and encounters: Carl Woese and my 30‐year research journey 灵感与邂逅:卡尔·沃斯和我30年的研究之旅

mLife Pub Date : 2022-12-18 DOI: 10.1002/mlf2.12050

Y. Ishino

引用次数: 0

Massive-scale genomic analysis reveals SARS-CoV-2 mutation characteristics and evolutionary trends. 大规模基因组分析揭示了严重急性呼吸系统综合征冠状病毒2型的突变特征和进化趋势。

mLife Pub Date : 2022-09-01 Epub Date: 2022-09-26 DOI: 10.1002/mlf2.12040

Yamin Sun, Min Wang, Wenchao Lin, Wei Dong, Jianguo Xu

{"title":"Massive-scale genomic analysis reveals SARS-CoV-2 mutation characteristics and evolutionary trends.","authors":"Yamin Sun, Min Wang, Wenchao Lin, Wei Dong, Jianguo Xu","doi":"10.1002/mlf2.12040","DOIUrl":"10.1002/mlf2.12040","url":null,"abstract":"The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in significant societal costs. Hence, an in-depth understanding of SARS-CoV-2 virus mutation and its evolution will help determine the direction of the COVID-19 pandemic. In this study, we identified 296,728 de novo mutations in more than 2,800,000 high-quality SARS-CoV-2 genomes. All possible factors affecting the mutation frequency of SARS-CoV-2 in human hosts were analyzed, including zinc finger antiviral proteins, sequence context, amino acid change, and translation efficiency. As a result, we proposed that when adenine (A) and tyrosine (T) bases are in the context of AM (M stands for adenine or cytosine) or TA motif, A or T base has lower mutation frequency. Furthermore, we hypothesized that translation efficiency can affect the mutation frequency of the third position of the codon by the selection, which explains why SARS-CoV-2 prefers AT3 codons usage. In addition, we found a host-specific asymmetric dinucleotide mutation frequency in the SARS-CoV-2 genome, which provides a new basis for determining the origin of the SARS-CoV-2. Finally, we summarize all possible factors affecting mutation frequency and provide insights into the mutation characteristics and evolutionary trends of SARS-CoV-2.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"1 3","pages":"311-322"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9538474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41176069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct gut microbiota and health outcomes in asymptomatic infection, viral nucleic acid test re-positive, and convalescent COVID-19 cases. 无症状感染者、病毒核酸检测重阳性和恢复期新冠肺炎病例的不同肠道微生物群和健康结果。

mLife Pub Date : 2022-06-01 Epub Date: 2022-06-15 DOI: 10.1002/mlf2.12022

Ruqin Lin, Mingzhong Xiao, Shanshan Cao, Yu Sun, Linhua Zhao, Xiaoxiao Mao, Peng Chen, Xiaolin Tong, Zheyuan Ou, Hui Zhu, Dong Men, Xiaodong Li, Yiqun Deng, Xian-En Zhang, Jikai Wen

{"title":"Distinct gut microbiota and health outcomes in asymptomatic infection, viral nucleic acid test re-positive, and convalescent COVID-19 cases.","authors":"Ruqin Lin, Mingzhong Xiao, Shanshan Cao, Yu Sun, Linhua Zhao, Xiaoxiao Mao, Peng Chen, Xiaolin Tong, Zheyuan Ou, Hui Zhu, Dong Men, Xiaodong Li, Yiqun Deng, Xian-En Zhang, Jikai Wen","doi":"10.1002/mlf2.12022","DOIUrl":"10.1002/mlf2.12022","url":null,"abstract":"Gut microbiota composition is suggested to associate with coronavirus disease 2019 (COVID-19) severity, but the impact of gut microbiota on health outcomes is largely unclear. We recruited 81 individuals from Wuhan, China, including 13 asymptomatic infection cases (Group A), 24 COVID-19 convalescents with adverse outcomes (Group C), 31 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) re-positive cases (Group D), and 13 non-COVID-19 healthy controls (Group H). The microbial features of Groups A and D were similar and exhibited higher gut microbial diversity and more abundant short-chain fatty acid (SCFA)-producing species than Group C. Group C was enriched with opportunistic pathogens and virulence factors related to adhesion and toxin production. The abundance of SCFA-producing species was negatively correlated, while Escherichia coli was positively correlated with adverse outcomes. All three groups (A, C, and D) were enriched with the mucus-degrading species Akkermansia muciniphila, but decreased with Bacteroides-encoded carbohydrate-active enzymes. The pathways of vitamin B6 metabolic and folate biosynthesis were decreased, while selenocompound metabolism was increased in the three groups. Specifically, the secondary bile acid (BA) metabolic pathway was enriched in Group A. Antibiotic resistance genes were common among the three groups. Conclusively, the gut microbiota was related to the health outcomes of COVID-19. Dietary supplementations (SCFAs, BA, selenium, folate, vitamin B6) may be beneficial to COVID-19 patients.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"1 2","pages":"183-197"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

gcCov: Linked open data for global coronavirus studies. gcCov：全球冠状病毒研究的关联开放数据。

mLife Pub Date : 2022-03-01 Epub Date: 2022-03-16 DOI: 10.1002/mlf2.12008

Wenyu Shi, Guomei Fan, Zhihong Shen, Chuan Hu, Juncai Ma, Yuanchun Zhou, Zhen Meng, Songnian Hu, Yuhai Bi, Liang Wang, Haiying Yu, Siru Lin, Xiuqiang Sun, Xinjiao Zhang, Dongmei Liu, Qinlan Sun, Linhuan Wu

引用次数: 0

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