mLife最新文献

{"title":"Novel plasmid pCM3 harboring the <i>aph(3)</i> gene confers phosphorylation-driven streptomycin resistance in <i>Clavibacter michiganensis</i>.","authors":"Xiaoli Xu, Cen Qian, Zhigang Hao, Meng Xie, Na Jiang, Jianqiang Li, Laixin Luo","doi":"10.1002/mlf2.70091","DOIUrl":"10.1002/mlf2.70091","url":null,"abstract":"<p><p>Antibiotic resistance in plant pathogens threatens sustainable crop protection, and yet, its molecular basis remains incompletely understood. We report that streptomycin resistance in <i>Clavibacter michiganensis</i> strain TX-0702 is mediated by a plasmid-borne aminoglycoside phosphotransferase, APH(3), encoded on an uncharacterized plasmid, pCM3. Functional and biochemical analyses demonstrate that APH(3) inactivates streptomycin through phosphorylation, establishing a phosphorylation-driven resistance mechanism in Gram-positive plant pathogens. Sequence analyses reveal that pCM3 carries mobile genetic elements, suggesting environmental dissemination of resistance genes in plant-associated microbes. These findings expand understanding of phytopathogen antibiotic resistance and plant microbiomes as potential resistance gene sources for agricultural, food, and human health safety.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 3","pages":"383-387"},"PeriodicalIF":6.7,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378819","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":"Harnessing microbial power to degrade hydrocarbon-based plastics.","authors":"Hui Li, Xuanyu Tao, Lina Sun, Aifen Zhou, Jizhong Zhou","doi":"10.1002/mlf2.70088","DOIUrl":"10.1002/mlf2.70088","url":null,"abstract":"<p><p>The growing global plastic waste crisis demands the development of urgent, effective, and sustainable solutions. While conventional recycling methods present intrinsic limitations, microbial biodegradation of plastic waste has emerged as a promising alternative. In this review, we explore the potential of using microorganisms to degrade major hydrocarbon-based plastic polymers and discuss key aspects of this rapidly advancing field, including (i) isolation and characterization of novel microorganisms and enzymes in hydrocarbon-based plastic biodegradation, (ii) development and streamlining of microbial consortia to improve hydrocarbon-based plastic biodegradation efficiency, and (iii) investigation of natural biodegradation processes to illustrate the relationship between plastic degradation and environmental influence. We highlight practical biotechnological approaches and advanced computational tools in hydrocarbon-based plastic degradation, as hydrocarbon-based plastic represents the highest proportion of plastic waste while still lacking effective conversion strategies. Our ultimate goal is to integrate microbial biodegradation strategies into modern waste-management systems and offer a feasible pathway toward a circular bioeconomy, one in which persistent plastic polymers are no longer treated as waste but are converted into renewable feedstocks that support sustainable resource recovery.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 3","pages":"263-281"},"PeriodicalIF":6.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378833","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":"Cefdinir reprograms Gram-positive bacteria to synergize with lysozyme against superbugs.","authors":"Qi Zhang, Yang Yang, Shuqi Li, Zhao Liu, Chun-Kit Lee, Chi-Bun Ko, Qian Zhao","doi":"10.1002/mlf2.70080","DOIUrl":"10.1002/mlf2.70080","url":null,"abstract":"<p><p>Multidrug-resistant (MDR) bacteria pose a critical global health threat, urgently requiring solutions. Cefdinir, the highest-selling third-generation cephalosporin but one now facing clinical obsolescence due to escalating resistance, is conventionally classified as a nascent cell wall synthesis inhibitor. This study challenges this understanding by demonstrating that cefdinir renders existing cell walls negatively charged, thereby synergizing with ubiquitous lysozyme and simultaneously restoring both agents' efficacy against a broad spectrum of MDR Gram-positive superbugs without driving resistance. Specifically, cefdinir is unexpectedly shown to post-transcriptionally increase the levels of clustered enzymes in lipoteichoic acid (LTA) and wall teichoic acid (WTA) synthesis pathways, including TarA, TarB, TarD, TarF, TarH, TarK, TarL, TarS, and FmtA, thereby enhancing cell wall electronegativity to remodel existing cell wall into a lysozyme-susceptible state, in which TarS is identified for the first time by mass spectrometry. The combination of cefdinir and lysozyme also significantly suppresses biofilm formation and minimizes <i>de novo</i> resistance mutations. Antibacterial efficacy of combination therapy is validated in both cell-based infection models and rat skin infection models, demonstrating strong translational potential. Given the established safety profiles of both agents, this sensitization strategy can be applied to human clinical research to combat MDR Gram-positive bacterial infections.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 3","pages":"355-368"},"PeriodicalIF":6.7,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378760","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":"Challenging the prokaryotic MGE-defense origin of eukaryotic RNA editing.","authors":"Yuange Duan, Qiuhua Xie, Jiajia Yang, Wanzhi Cai, Hu Li","doi":"10.1002/mlf2.70084","DOIUrl":"10.1002/mlf2.70084","url":null,"abstract":"","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 3","pages":"296-300"},"PeriodicalIF":6.7,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378802","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":"Rapid and quantitative phage susceptibility test by ramanome.","authors":"Xiao Han, Xiaofu Wan, Yang Zhou, Xiaoting Fu, Xiaoshan Zheng, Bo Gao, Shi Huang, Anle Ge, Jiadong Huang, Hongzhou Lu, Jian Xu","doi":"10.1002/mlf2.70089","DOIUrl":"10.1002/mlf2.70089","url":null,"abstract":"<p><p>Antimicrobial resistance poses an escalating global threat, renewing interest in bacteriophage therapy as a precision alternative to antibiotics. However, clinical translation remains hindered by the lack of rapid and quantitative phage susceptibility testing (PST) platforms capable of evaluating host range, infection potency, and effective multiplicity of infection (MOI). Here, we present a ramanome-based phage susceptibility test (RPST), a phenotypic platform that captures infection-induced remodeling of bacterial macromolecular composition to unify these diagnostic requirements within a single workflow. RPST integrates four Raman biomarkers into a Composite Infection Index (CII), enabling rapid and lysis-independent discrimination between susceptible and resistant bacterial populations within ~1 h, with 96.0% categorical concordance (24/25) to plaque assays. As a continuous population-level metric, CII quantifies the proportion of infected cells, allowing quantitative ranking of phage potency against shared hosts. By resolving CII trajectories across the MOI and time, RPST further determines the minimal effective MOI, which is the lowest phage-to-bacterium ratio sustaining self-propagating infection, thereby defining the lower boundary for therapeutic feasibility. Together, these capabilities transform PST from static compatibility assays into a dynamic and quantitative framework that bridges <i>in vitro</i> infectivity assessment and infection dynamics relevant to phage therapy.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 3","pages":"369-382"},"PeriodicalIF":6.7,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378808","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":"Direct interaction between MreB and the RodA-PBP2 complex organizes lateral cell wall synthesis in <i>Escherichia coli</i>.","authors":"Rui Zhan, Han Gong, Ying Li, Xiangdong Chen, Joe Lutkenhaus, Shishen Du","doi":"10.1002/mlf2.70079","DOIUrl":"10.1002/mlf2.70079","url":null,"abstract":"<p><p>The elongasome, or the Rod complex, orchestrates lateral peptidoglycan (PG) synthesis in many rod-shaped bacteria. It consists of the actin-like protein MreB, the PG synthase RodA-PBP2 complex, as well as MreCD and RodZ. Although the loss or disruption of any elongasome component results in a loss of rod shape, previous studies found that a constitutively active RodA-PBP2 complex can partially bypass the requirement of MreCD and RodZ for lateral PG synthesis and restore rod shape. However, how MreB is connected to RodA-PBP2 under this situation and whether this linkage is important for elongasome activity in wild-type cells remain unknown. Here, we report the isolation of additional RodA and PBP2 variants that can partially compensate for the absence of MreCD and RodZ in lateral PG synthesis. Taking advantage of these mutants and guided by an AlphaFold 3 structural model of the elongasome complex, we discover that both the cytoplasmic region of PBP2 and the C-terminal tail of RodA interact with MreB. Moreover, disruption of these interactions results in a loss of rod shape, indicating that the interaction between MreB and RodA-PBP2 is critical for elongasome function. Taken together, our results uncover how the MreB cytoskeleton is coupled to RodA-PBP2 to organize lateral PG synthesis. These findings provide mechanistic insights into cell wall biogenesis in bacteria and offer strategies for the development of new antibiotics targeting the elongasome.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 3","pages":"325-338"},"PeriodicalIF":6.7,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378779","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":"Microbially driven organic carbon cycling at the land-sea interface: Advances and an integrated study framework.","authors":"Quanrui Chen, Kai Tang, Zhili He, Meng Li, Jun Yang, Weidong Zhai, Qiang Zheng, Nianzhi Jiao","doi":"10.1002/mlf2.70082","DOIUrl":"10.1002/mlf2.70082","url":null,"abstract":"<p><p>The land-sea interface is a vital component of global biogeochemical cycles, where microorganisms drive the cycling of carbon, nitrogen, and sulfur. This review synthesizes the research progress from representative land-sea interfaces to elucidate how the microbial community structure and metabolic function influence the mobilization, transformation, and retention of organic carbon. Here, we also review the mechanisms underlying carbon cycle dynamics and emphasize the role of coupled biogeochemical cycles and climate change. A key focus is the synergistic interaction among the marine microbial carbon pump (MCP), the soil MCP, and the mineral-associated carbon pump, hereafter referred to as the land-sea MCP framework. We further propose an integrated study framework, based on measurable parameters such as carbon use efficiency and bacterial growth efficiency, to link microbial processes to long-term carbon sequestration at the land-sea interface.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 3","pages":"282-295"},"PeriodicalIF":6.7,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378839","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":"Emerging role of metagenomic next-generation sequencing in infectious disease diagnostics: Clinical integration and future directions.","authors":"Tingting Fang, Feifei Yuan, Yu Chen, Na Li, Yao Zhang, Haixia Liu, Xingchen Liu, Qing Miao, Bijie Hu","doi":"10.1002/mlf2.70078","DOIUrl":"10.1002/mlf2.70078","url":null,"abstract":"<p><p>Infectious disease diagnostics has been transformed by metagenomic next-generation sequencing (mNGS), an unbiased approach that detects bacteria, viruses, fungi, and parasites in a single assay. By sequencing all nucleic acids in a sample, mNGS overcomes the narrow detection scope and slow turnaround of conventional tests, substantially improving pathogen detection. In conditions such as meningitis/encephalitis, sepsis, and pneumonia, mNGS frequently identifies etiologies missed by routine diagnostic tests, thereby facilitating earlier pathogen-directed therapy and, in selected settings, improving clinical management and outcomes. This approach is particularly valuable for immunocompromised, pediatric, and intensive care unit (ICU) patients with atypical infections. Currently, clinical mNGS workflows primarily rely on short-read sequencing platforms (e.g., Illumina), whereas long-read platforms (e.g., Nanopore, PacBio) offer advantages for rapid or high-resolution applications. Optimized bioinformatics and stringent quality control are essential for reliable results. Beyond clinical diagnostics, mNGS provides valuable genetic data on antimicrobial resistance (AMR) and pathogen phylogeny, supporting public health and outbreak surveillance (e.g., wastewater monitoring and variant tracking). Current challenges include distinguishing colonization from infection, interpreting sequencing data quantitatively, and reducing cost and turnaround time. Looking ahead, emerging strategies such as targeted panels, rapid automated workflows, and host‑response integration are expected to further shorten time‑to‑result and improve diagnostic specificity. Parallel progress in ethical and regulatory frameworks remains essential to ensure responsible implementation. To support clinical adoption, a standardized framework for clinical interpretation of mNGS results, together with associated training, has been developed and implemented. Overall, mNGS is likely to become an increasingly important component of infectious disease diagnostics, with ongoing innovations expected to broaden its clinical and epidemiological impact.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 2","pages":"148-163"},"PeriodicalIF":6.7,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13131327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824911","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":"The synthetic estradiol analog E0703 enhances <i>Akkermansia muciniphila</i> growth for radiation-induced intestinal damage repair.","authors":"Zhexin Ni, Ziqiao Yan, Mingyang Chang, Yangshuo Li, Zebin Liao, Tiantian Xia, Zhijie Bai, Ningning Wang, Chaoji Huangfu, Dezhi Sun, Yangyi Hu, Liangliang Zhang, Feiran Hao, Yongqi Dou, Pan Shen, Wei Zhou, Yue Gao","doi":"10.1002/mlf2.70071","DOIUrl":"10.1002/mlf2.70071","url":null,"abstract":"<p><p>The development of safe and effective radioprotective agents with minimal side effects, particularly for high-dose exposure, remains a global priority. E0703, a novel steroidal compound structurally derived from estradiol, has shown promising radioprotective efficacy with limited estrogenic activity in prior pharmacodynamic studies. In this study, E0703 was found to significantly increase the abundance of <i>Akkermansia muciniphila</i> (AKK) in the intestines of both irradiated and non-irradiated mice. Co-administration of E0703 and AKK markedly improved the 7-day survival rate of mice exposed to a lethal 8.5 Gy dose of radiation. E0703 induced beneficial transcriptional changes in AKK, with enrichment in metabolic pathways such as amino acid biosynthesis, aminoacyl-tRNA biosynthesis, the tricarboxylic acid (TCA) cycle, and fatty acid biosynthesis. These alterations supported the production of glucosamine 6-phosphate (GlcN-6-P) by AKK, which contributed to intestinal tissue regeneration following irradiation. Single-cell transcriptomic analysis revealed that E0703 significantly increased the proportion of intestinal stem cells and goblet cells by Day 5 post irradiation. Mechanistically, E0703 modulated the oxidative phosphorylation pathway in these cell types, including regulation of Muc2 production. E0703 also enhanced AKK abundance in irradiated mice, particularly in the presence of mucin, thereby elevating the availability of GlcN-6-P-a critical substrate for intestinal organoid repair. These findings indicate that E0703 exerts direct effects on goblet cells and AKK, promoting host-microbe interactions that facilitate intestinal regeneration and improve survival following radiation exposure.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 2","pages":"199-216"},"PeriodicalIF":6.7,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13131332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825118","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":"Quinolone tolerance in <i>Escherichia coli</i> due to defects in the adenosine ribonucleotides <i>de novo</i> biosynthesis pathway.","authors":"Weiwei Zhu, Yuejuan Nong, Jie Su, Jingwen Yang, Lina Ma, Yunxin Xue, Dai Wang, Jianjun Niu, Karl Drlica, Xilin Zhao","doi":"10.1002/mlf2.70059","DOIUrl":"10.1002/mlf2.70059","url":null,"abstract":"<p><p>Central carbon metabolism is thought to link reactive oxygen species (ROS) with antibiotic-mediated bacterial death. During enrichment screening of <i>Escherichia coli</i> with the first-generation quinolone oxolinic acid, unstable antibiotic-tolerant mutants containing deficiencies in <i>purB</i> were obtained. Examination of a stable deletion mutant of <i>purA</i>, a gene functionally related to <i>purB</i>, revealed reduced lethality of oxolinic acid and ciprofloxacin. This deletion mutation had little effect on the minimal inhibitory concentration (MIC) of quinolones, thereby demonstrating that the observed protection from killing was attributable to antibiotic tolerance. AMP synthesis was blocked by the Δ<i>purA</i> mutation, and ciprofloxacin tolerance was reversed by exogenous AMP supplementation. Because AMP is a precursor of ATP, interference with ATP synthesis occurs in the Δ<i>purA</i> mutant. RNA-Seq analysis showed that, prior to antibiotic stress, transcript levels of NADH:quinone oxidoreductase genes were reduced by the <i>purA</i> deficiency, thereby predisposing <i>E. coli</i> to antibiotic tolerance through reduced respiration. During ciprofloxacin exposure, the <i>purA</i> deficiency also suppressed the surge in expression of tricarboxylic acid (TCA) cycle and ATP synthesis genes, as well as the accumulation of intracellular ATP and ROS. Thus, wild-type PurA, and by extension the downstream enzyme PurB, directs AMP toward an antibiotic-mediated, ROS-dependent death pathway. Overall, defects in PurA/PurB-mediated adenosine ribonucleotides <i>de novo</i> biosynthesis reveal a novel quinolone tolerance mechanism that is initiated outside central carbon metabolism; tolerance is likely attributable to a limited supply of AMP, resulting in reduced ATP synthesis and suppression of ROS accumulation.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"5 2","pages":"217-228"},"PeriodicalIF":6.7,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13131326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825037","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}