mLife最新文献

{"title":"A hot origin of dissimilatory sulfite reduction catalyzed by DsrAB in the Paleoarchean Era.","authors":"Lingyun Tang, Zhenhao Luo, Shaoming Gao, Zhiliang Lin, Mengqi Sun, Runsheng Li, Shu-Hong Gao, Geng Wu, Yiliang Li, Linan Huang, Lu Fan","doi":"10.1002/mlf2.70066","DOIUrl":"10.1002/mlf2.70066","url":null,"abstract":"<p><p>Dissimilatory sulfite reduction (DSR) has been essential to microbial energy metabolism in the biogeochemical sulfur cycle since the Paleoarchean Era. However, due to the lack of an integrated assessment of geological record and genomic data, the evolutionary origin of DSR remains elusive in terms of time, habitat, and genetic basis. In this study, we reconstructed the evolutionary pathways and the ancestral sequences of Dsr proteins by mining metagenomes ranging from mesothermal to hyperthermal environments. A phylogenetic analysis of the key catalytic enzyme, DsrAB, and other Dsr proteins indicates that the earliest and most basic functional cascade, DsrABCNM, emerged prior to the latest common ancestor of several basal branching DsrAB clusters encoded by bacteria and archaea. Using a molecular dating strategy that calibrates the protein tree with a species tree, we predicted that the DSR originated 3.508 billion years ago (Ga). This finding strongly confirms the earliest geological evidence of DSR ( ~ 3.47 Ga). Further predictions from ancestral sequence reconstruction indicate that the optimal catalytic temperature of DsrA at the time of DSR origin was approximately 73°C, which is consistent with the petrographic and geochemical evidence in early Archean hydrothermal deposits. After its hot origin, DsrA diversified into subclades that adapted to various temperature levels following the Great Oxidation Event. This is exemplified by the evolution of the reductive archaeal-type DsrA. Our results synchronize the molecular ages with the geological record, which advances our understanding of the earliest DSR systems and highlights the enzymatic adaptations of microbial life in the Archean biosphere.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 1","pages":"108-121"},"PeriodicalIF":6.7,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329025","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}

{"title":"Embracing the \"Microbiology+\" era.","authors":"Wei Qian, Jizhong Zhou","doi":"10.1002/mlf2.70074","DOIUrl":"10.1002/mlf2.70074","url":null,"abstract":"","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 1","pages":"1-2"},"PeriodicalIF":6.7,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328727","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}

{"title":"Prokaryotic defense systems: Diversity and evolutionary adaptation.","authors":"Changjialian Yang, Luyao Gong, Jing Guo, Hua Xiang","doi":"10.1002/mlf2.70068","DOIUrl":"10.1002/mlf2.70068","url":null,"abstract":"<p><p>Bacteriophages and archaeal viruses are the most abundant biological entities on Earth. Through a long-standing co-evolutionary arms race, they have driven the emergence of a diverse repertoire of prokaryotic defense systems. This review summarizes these systems, highlighting their diverse antiviral mechanisms across distinct stages of viral infection, from surface barriers and inducible innate responses to specific adaptive defenses, and the intricate interplay between these defense strategies. By examining host-virus counter defense dynamics, the trade-off between survival benefit and adaptive cost, the co-evolution of RNA and protein components, and the comparison with eukaryotic immune systems, we underscore the intrinsic complexity and evolutionary plasticity of prokaryotic antiviral immunity. A deeper understanding of these processes and mechanisms will not only shed light on the origins and evolution of the immune system but also provide valuable opportunities for the development of biotechnological tools.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 1","pages":"3-16"},"PeriodicalIF":6.7,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328755","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}

{"title":"Pressure-dependent adaptation strategies implied by the dissimilatory iron reducer <i>Orenia metallireducens</i> Z6.","authors":"Shuyi Li, Jiahao Pei, Jiasong Fang, Rulong Liu, Yuli Wei, Xianyu Huang, Guang Yang, Min Liu, Qin Lin, Robert R Sanford, Hongbo Shao, Yongguang Jiang, Yidan Hu, Zhou Jiang, Qi Feng, Yu He, Chenxi Zhang, Yizhou Fan, Yiran Dong, Liang Shi","doi":"10.1002/mlf2.70070","DOIUrl":"10.1002/mlf2.70070","url":null,"abstract":"<p><p>Tolerance of high hydrostatic pressure (HHP) is the hallmark of deep subsurface microorganisms, while its mechanisms remain under-investigated. This study explores HHP adaptation in the piezotolerant bacterium <i>Orenia metallireducens</i> across its near-full pressure range (0.1-40 MPa). At inhibitory pressure (40 MPa), the organism redirected carbon flux toward more favorable energy generation and biosynthesis using ferric mineral as the \"electron sink.\" Furthermore, both universal and pressure-dependent strategies enabled the organism to withstand varying pressures. These findings highlight the role of iron minerals in microbial HHP adaptation and reveal novel survival strategies, advancing our understanding of deep-life evolution and biogeochemical impacts.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 1","pages":"122-125"},"PeriodicalIF":6.7,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328735","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}

{"title":"Profiling the host defense responses against <i>Candida auris</i> in a reliable <i>Drosophila melanogaster</i> infection model.","authors":"Jie Li, Guangsheng Chen, Xiangkang Zeng, Jiaxin Lin, Xiaoqing Chen, Wenqiang Wang, Yueru Tian, Xinhua Huang, Yun Zou, Ming Guan, Zhiyi He, Hailei Wang, Changbin Chen, Lei Pan","doi":"10.1002/mlf2.70038","DOIUrl":"10.1002/mlf2.70038","url":null,"abstract":"<p><p>The \"superbug\" <i>Candida auris</i> has been ranked as a priority fungal pathogen and is becoming a serious threat to public health. However, the underlying mechanisms of real-world pathogen-host interactions remain elusive, in part due to the lack of powerful immunocompetent animal models. Here, we report that selected wild-type strains of <i>Drosophila melanogaster</i> can be developed as a promising infection model to recapitulate <i>C. auris</i> systemic infection. The systemic and organ-specific responses to <i>C. auris</i> infection <i>in vivo</i> were evaluated, as well as the corresponding transcriptional profiling. Our findings confirmed that Toll and JAK-STAT signaling pathways mediate antifungal responses in the <i>Drosophila</i> model following <i>C. auris</i> infection. Moreover, we identified certain conserved novel factors required for host-<i>C. auris</i> interactions, highlighting the fly model's potential to reveal subtle immune mechanisms not readily observed in mammalian systems. Taken together, our work demonstrates that wild-type <i>Drosophila</i> offers a robust immunocompetent animal model for further in-depth investigation of dynamic <i>C. auris</i>-host interactions <i>in vivo</i>.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 1","pages":"51-67"},"PeriodicalIF":6.7,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328762","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}

{"title":"Berberrubine inhibits <i>Helicobacter pylori</i> by inducing oxidative stress and impairing membrane integrity.","authors":"Minzhi Jiang, Changyu Wang, Kai Wang, Xinchi Feng, Gen Li, Yu Jiang, Xue Wang, Shijie Cao, Liqin Ding, Shuangyu Bi, Feng Qiu, Shuang-Jiang Liu, Chang Liu","doi":"10.1002/mlf2.70061","DOIUrl":"10.1002/mlf2.70061","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> is a major gastric pathogen with increasing antibiotic resistance, creating an urgent need for new therapeutic strategies. We screened 37 pure compounds and 9 herbal extracts for anti-<i>H. pylori</i> activity and identified berberrubine as the most potent agent, with a minimum inhibitory concentration of 11 μg/ml. Berberrubine exhibited bacteriostatic effects by inducing oxidative stress and disrupting membrane integrity, as demonstrated by transcriptomic analysis, reactive oxygen species (ROS) accumulation, and structural damage, all of which were alleviated by the antioxidant N-acetylcysteine. Similar inhibitory effects were observed in <i>Escherichia coli</i>, indicating broader antimicrobial potential. This study provides the mechanistic evidence of berberrubine's activity against <i>H. pylori</i>, highlighting its promise as a candidate for development into alternative therapies to address antibiotic resistance.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 1","pages":"126-130"},"PeriodicalIF":6.7,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328549","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}

{"title":"Antibiotic resistance mediated by site-specific mutations in the multidrug efflux transporter CmeB of zoonotic pathogen <i>Campylobacter</i>.","authors":"Xiaolong Lin, Mengyu Zhao, Jianhong Gan, Haozheng Li, Min He, Fang Yang, Renqiao Wen, Tiejun Zhang, Quan Zhou, Ke Wu, Jinpeng Li, Chengyao Hou, Yang Cao, Hongning Wang, Yizhi Tang","doi":"10.1002/mlf2.70051","DOIUrl":"10.1002/mlf2.70051","url":null,"abstract":"<p><p>The resistance‒nodulation‒division (RND) family of multidrug efflux transporters is widely distributed in Gram-negative bacteria. Although their roles in mediating antibiotic resistance have been well known, our understanding of how they are altered to augment bacterial adaptation to antibiotic selection remains at an infancy stage. Here, we report the identification of a mutation-based mechanism that empowers the function of the CmeB efflux protein, an RND-type transporter in the zoonotic pathogen <i>Campylobacte</i>r. During our surveillance study, we identified <i>Campylobacter</i> isolates that were phenotypically resistant to florfenicol but lacked known florfenicol resistance mechanisms. Using natural transformation and whole genome sequencing, we first linked the phenotype to sequence polymorphisms in the <i>cmeB</i> and subsequently demonstrated that both the T136A and M292I mutations in CmeB are required for the resistance phenotype. The mutations elevated <i>Campylobacter</i> resistance to florfenicol, ciprofloxacin, and other classes of antimicrobial agents. Structural modeling and molecular dynamics simulations revealed that the two residues were localized in the drug-binding pocket of CmeB, and the T136A and M292I substitutions enhanced hydrophobic interactions, stabilized CmeB-antibiotic binding, and lessened steric hindrance in the drug-binding pocket, thereby facilitating antibiotic extrusion by CmeB. Analysis of the <i>Campylobacter</i> genomic sequences deposited in the NCBI database revealed that T136A- and M292I-harboring isolates were found in 35 different countries and associated with various host species, indicating the widespread distribution and clinical relevance of the two mutations. Together, these results identified a new mechanism underlying CmeB-mediated multidrug resistance and provide a potential target for clinical surveillance of antibiotic-resistant <i>Campylobacter</i>.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 1","pages":"83-98"},"PeriodicalIF":6.7,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328407","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}

{"title":"Structures and mechanism of E2-CBASS anti-phage system.","authors":"Jun Xiao, Yan Yan, Jing Li, Greater Kayode Oyejobi, Dongyang Lan, Bin Zhu, Zhiming Wang, Longfei Wang","doi":"10.1002/mlf2.70052","DOIUrl":"10.1002/mlf2.70052","url":null,"abstract":"<p><p>Bacteria deploy diverse innate immune systems to combat bacteriophage infections. The cyclic-oligonucleotide-based anti-phage signaling system (CBASS) is a type of innate prokaryotic immune system. CBASS synthesizes cyclic-oligonucleotide through cGAS/DncV-like nucleotidyltransferases (CD-NTases) to activate downstream effectors, which kill bacteriophage-infected bacteria, thereby stopping phage spread. One major class of CBASS contains a homolog of eukaryotic ubiquitin-conjugating enzymes, either as an E1-E2 fusion or a single E2 enzyme. Both enzymes function by regulating CD-NTase activity. Currently, many structures of CD-NTases have been reported, but there are only a few reports of structures where CD-NTases form complexes with the associated E2. In this study, we analyzed the length and classification of the CD-NTase in two types of type II CBASS-E1E2/JAB-CBASS and E2-CBASS. We found that the CD-NTase in E2-CBASS is longer and predominantly belongs to clade G. We also present the structure of the <i>Sm</i>CdnG-<i>Sm</i>E2 complex with the bound GTP substrate, which indicates the conservation of the donor binding pattern. Interestingly, we discovered that <i>Sm</i>CdnG contains a conserved C-terminal α-helix and β-sheet structure, which is uniquely involved in forming a complex with <i>Sm</i>E2. We also found that the structure of the E2 protein in the E2-CBASS system is highly conserved. Altogether, we provide mechanistic insights into the E2-CBASS system.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 1","pages":"99-107"},"PeriodicalIF":6.7,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328694","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}

{"title":"CRISPR-based genome editing reveals the roles of efflux pumps in <i>Mycobacterium abscessus</i>.","authors":"Sishang Li, Aofei Duan, Lanyue Zhang, Chunliang Wang, Meiyi Yan, Gai-Xian Ren, Li-Ping Pan, Yi-Cheng Sun","doi":"10.1002/mlf2.70048","DOIUrl":"10.1002/mlf2.70048","url":null,"abstract":"<p><p><i>Mycobacterium abscessus</i>, one of the most antimicrobial-resistant bacteria, is increasingly recognized as the cause of infections that are difficult to treat. Novel genetic manipulation tools are required to elucidate the biology, pathogenesis, and antibiotic resistance mechanisms of <i>M. abscessus</i>. In this study, we modified the method used to prepare <i>M. abscessus</i> electrocompetent cells to achieve efficient transformation, and then optimized the CRISPR-Cas9-assisted genome-editing tools to allow efficient genetic manipulation. Using these tools, we constructed 66 efflux pump mutants of <i>M. abscessus</i> and investigated their roles in drug resistance and virulence. We found that different efflux pumps play distinct roles in drug resistance and survival in <i>Galleria mellonella</i> larvae. Finally, we confirmed that MAB_2806-2807, involved in transportation of triacylglycerides, is vital for the drug resistance and virulence of <i>M. abscessus</i>. The molecular biology tools developed in this study will facilitate molecular research on <i>M. abscessus</i>. In addition, the study on efflux pumps might provide new targets for the development of new drugs and treatment regimens for <i>M. abscessus</i> infection.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 1","pages":"68-82"},"PeriodicalIF":6.7,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328775","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}

{"title":"Oral pretreatment with <i>Escherichia coli</i> Nissle 1917 enhances the host's defense against influenza A virus infection.","authors":"Di Wang, Longhai Yu, Qi Lu, Meiqing Han, Baikui Wang, Xianqi Peng, Min Yue, Yan Li","doi":"10.1002/mlf2.70050","DOIUrl":"10.1002/mlf2.70050","url":null,"abstract":"<p><p>Influenza A viruses (IAVs) pose a significant threat to global health, causing annual epidemics and occasional pandemics with substantial morbidity and mortality. Despite the availability of vaccines and antiviral therapies, the development of novel preventive and therapeutic strategies remains a critical research focus. In this study, we evaluated the protective effects of orally administering <i>Escherichia coli</i> Nissle 1917 in IAV-infected mice and elucidated its mechanisms of action by analyzing cecal microbiota and plasm metabolome profiles. Oral administration of <i>E. coli</i> Nissle 1917 alleviated respiratory symptoms, reduced weight loss, and mitigated pathological injury in mice infected with H9N2 or H1N1 IAV. These protective effects were mediated through the modulation of gut microbiota diversity, which increased the abundance of <i>Bacteroides</i> and <i>Akkermansia</i>, correlating with elevated pipecolic acid levels and ultimately aiding in defense against IAV infection in mice. Notably, we identified that the circulating metabolic molecule pipecolic acid plays a significant role in fighting IAV infection. Our findings suggest the potential usefulness of <i>E. coli</i> Nissle 1917 or pipecolic acid in influenza prevention.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"4 6","pages":"666-682"},"PeriodicalIF":6.7,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890802","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}