IF 6.7

mLife Pub Date : 2025-12-25 eCollection Date: 2025-12-01 DOI: 10.1002/mlf2.70044

Shihao Song, Jingyun Liu, Bing Wang, Yang Si, Hongguang Han, Xiuyun Sun, Mingfang Wang, Binbin Cui, Guangliang Wu, Yongliang Huo, Liangxiong Xu, Beile Gao, Liang Yang, Xiaoxue Wang, Lian-Hui Zhang, Yinyue Deng

{"title":"Cis-2-decenoic acid modulates Pseudomonas aeruginosa virulence through a noncanonical transcriptional regulator.","authors":"Shihao Song, Jingyun Liu, Bing Wang, Yang Si, Hongguang Han, Xiuyun Sun, Mingfang Wang, Binbin Cui, Guangliang Wu, Yongliang Huo, Liangxiong Xu, Beile Gao, Liang Yang, Xiaoxue Wang, Lian-Hui Zhang, Yinyue Deng","doi":"10.1002/mlf2.70044","DOIUrl":"10.1002/mlf2.70044","url":null,"abstract":"Diffusible signal factor (DSF)-family quorum sensing (QS) signals are widely utilized by many pathogenic bacteria to modulate various biological functions and virulence. Previous studies showed that cis-2-decenoic acid (cis-DA) is involved in the modulation of biofilm dispersion in Pseudomonas aeruginosa, but the regulatory mechanism is unclear. Here, we report that cis-DA regulates the physiology and virulence of P. aeruginosa through FadD1, a long-chain fatty acid-CoA ligase. cis-DA specifically binds to FadD1 and enhances the binding ability of FadD1 to the target gene promoter DNA regions. Further analysis showed that FadD1 is a global regulatory factor that controls the transcription of various target genes. Moreover, FadD1 showed catalytic activity on cis-2-dodecenoic acid (BDSF) of Burkholderia cenocepacia and enhanced the competitiveness of P. aeruginosa. Together, our work presents a new DSF-type QS signaling system in P. aeruginosa, which is highlighted by the signal receptor evolved from a canonical enzyme of fatty acid metabolism.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"4 6","pages":"625-639"},"PeriodicalIF":6.7,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890706","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

Phage therapy of perinephric abscess in kidney transplantation recipients caused by drug-resistant Pseudomonas aeruginosa. 耐药铜绿假单胞菌所致肾移植受者肾周脓肿的噬菌体治疗。

IF 6.7

mLife Pub Date : 2025-12-25 eCollection Date: 2025-12-01 DOI: 10.1002/mlf2.70042

Jiazhen Liu, Shuguang Lu, Juan Bao, Jing Wang, Yali Gong, Bo He, Yuhao Zhu, Zhuojun Zhong, Shiru Li, Linlin Li, Na Li, Mengjun Cheng, Ming Li, Mengyu Shen, Nannan Wu, Tongyu Zhu, Shuai Le

引用次数: 0

CcpA promotes Staphylococcus aureus virulence by directly controlling staphyloxanthin production. CcpA通过直接控制葡萄黄素的产生来促进金黄色葡萄球菌的毒力。

IF 6.7

mLife Pub Date : 2025-12-25 eCollection Date: 2025-12-01 DOI: 10.1002/mlf2.70040

Xian Chen, Huagang Peng, Xiancai Rao, Yi Yang, Keting Zhu, Zhen Hu, Shu Li, Xiaonan Huang, Feng Lin, Jianghong Wu, Weilong Shang, Renjie Zhou, Yifan Rao

{"title":"CcpA promotes Staphylococcus aureus virulence by directly controlling staphyloxanthin production.","authors":"Xian Chen, Huagang Peng, Xiancai Rao, Yi Yang, Keting Zhu, Zhen Hu, Shu Li, Xiaonan Huang, Feng Lin, Jianghong Wu, Weilong Shang, Renjie Zhou, Yifan Rao","doi":"10.1002/mlf2.70040","DOIUrl":"10.1002/mlf2.70040","url":null,"abstract":"Staphylococcus aureus is a notorious opportunistic pathogen with remarkable adaptability, enabling it to infect virtually every human tissue. Staphyloxanthin (STX), a critical virulence factor, contributes to S. aureus oxidative damage. However, the regulatory mechanism of STX production is incompletely understood. This study provides mechanistic insights into the role of catabolite control protein A (CcpA) in STX production. ccpA deletion considerably reduced STX yield in S. aureus strains with diverse genetic lineages. Western blot showed that CcpA inactivation did not alter SigB expression levels in S. aureus. Gene reporter and electrophoretic mobility shift assays revealed the direct control of CcpA on the expression of the crtOPQMN operon, which encodes enzymes for step-wise STX biosynthesis. Moreover, CcpA deficiency remarkably impaired bacterial tolerance to H2O2-mediated killing, decreased survival in whole-blood treatment, and diminished persistence in macrophages. In mouse bacteremia and skin abscess models, CcpA was shown to enhance S. aureus virulence. Notably, inhibition of CcpA with Ag+ synergized with vancomycin to combat vancomycin-intermediate S. aureus infections in vivo. Our findings establish CcpA as a SigB-independent regulator of STX production, suggesting that targeting CcpA could be a promising antibiotic synergistic strategy for the management of multidrug-resistant S. aureus infections.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"4 6","pages":"653-665"},"PeriodicalIF":6.7,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890654","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

Modulation of host cell pathways by Coxiella burnetii Dot/Icm effectors. 伯氏杆菌Dot/Icm效应物对宿主细胞通路的调节。

IF 6.7

mLife Pub Date : 2025-12-25 eCollection Date: 2025-12-01 DOI: 10.1002/mlf2.70058

Jingya Yuan, Yong Zhang, Lei Song, Zhao-Qing Luo

{"title":"Modulation of host cell pathways by Coxiella burnetii Dot/Icm effectors.","authors":"Jingya Yuan, Yong Zhang, Lei Song, Zhao-Qing Luo","doi":"10.1002/mlf2.70058","DOIUrl":"10.1002/mlf2.70058","url":null,"abstract":"Coxiella burnetii, the etiological agent of Q fever, is a significant intracellular bacterial pathogen. C. burnetii is a highly infectious pathogen that primarily targets pulmonary alveolar macrophages during natural infection. It can then disseminate to macrophages in other tissues and organs, leading to chronic infections. C. burnetii is capable of infecting a variety of cultured cells, including primary macrophages, macrophage-like cells, epithelial cells, and fibroblasts. The virulence of C. burnetii is entirely dependent on the Dot/Icm type IVB secretion system (T4BSS), which delivers effectors into infected cells to modulate cellular pathways for the biogenesis of the Coxiella-containing vacuole that supports its intracellular replication. A deeper understanding of how C. burnetii exploits host cell processes is essential for developing novel therapeutic strategies to combat infections caused by this important pathogen. This review summarizes the historical milestones and recent advances in our understanding of the structure and function of the C. burnetii Dot/Icm system and its effectors.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"4 6","pages":"579-598"},"PeriodicalIF":6.7,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890795","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

ZapA uses a two-pronged mechanism to facilitate Z ring formation in Escherichia coli. ZapA利用双管齐下的机制促进大肠杆菌中Z环的形成。

IF 6.7

mLife Pub Date : 2025-12-21 eCollection Date: 2025-12-01 DOI: 10.1002/mlf2.70037

Yuanyuan Cui, Han Gong, Di Yan, Hao Li, Wenjie Yang, Ying Li, Xiangdong Chen, Joe Lutkenhaus, Sheng-You Huang, Xinxing Yang, Shishen Du

{"title":"ZapA uses a two-pronged mechanism to facilitate Z ring formation in Escherichia coli.","authors":"Yuanyuan Cui, Han Gong, Di Yan, Hao Li, Wenjie Yang, Ying Li, Xiangdong Chen, Joe Lutkenhaus, Sheng-You Huang, Xinxing Yang, Shishen Du","doi":"10.1002/mlf2.70037","DOIUrl":"10.1002/mlf2.70037","url":null,"abstract":"The tubulin-like protein FtsZ assembles into the Z ring that leads to the assembly and activation of the division machinery in most bacteria. ZapA, a widely conserved protein that interacts with FtsZ, plays a pivotal role in organizing FtsZ filaments into a coherent Z ring. Previous studies revealed that ZapA forms a dumbbell-like tetramer that binds cooperatively to FtsZ filaments and aligns them in parallel, leading to the straightening and organization of FtsZ filament bundles. However, how ZapA interacts with FtsZ remains obscure. Here, we reveal that ZapA uses a two-pronged mechanism to interact with FtsZ to facilitate Z ring formation in Escherichia coli. We find that mutations affecting surface-exposed residues at the junction between adjacent FtsZ subunits in a filament as well as in an N-terminal motif of FtsZ weaken its interaction with ZapA in vivo and in vitro, indicating that ZapA binds to these regions of FtsZ. Consistent with this, ZapA prefers FtsZ polymers over monomeric FtsZ molecules and site-specific crosslinking confirmed that the dimer head domain of ZapA is in contact with the junction of FtsZ subunits. As a result, disruption of the putative interaction interfaces between FtsZ and ZapA abolishes the midcell localization of ZapA. Taken together, our results suggest that ZapA tetramers grab the N-terminal tails of FtsZ and bind to the junctions between FtsZ subunits in the filament to straighten and crosslink FtsZ filaments into the Z ring.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"4 6","pages":"604-624"},"PeriodicalIF":6.7,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890814","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

RNA editing system: Balancing altruistic antiviral defense and fitness trade-offs in fungi. RNA编辑系统：平衡真菌的利他抗病毒防御和适应性权衡。

IF 6.7

mLife Pub Date : 2025-12-18 eCollection Date: 2025-12-01 DOI: 10.1002/mlf2.70057

Yanfei Du, Daohong Jiang, Huiquan Liu

引用次数: 0

Dual glycosylation of wall teichoic acid modulates the O-antigen pattern and virulence in serovar 4b Listeria monocytogenes. 壁壁壁酸双糖基化调节单核细胞增生李斯特菌血清型4b的o抗原模式和毒力。

IF 6.7

mLife Pub Date : 2025-12-16 eCollection Date: 2025-12-01 DOI: 10.1002/mlf2.70041

Hao Yao, Yuting Wang, Ruochen Wang, Zhengnan Dong, Zhenhua Wu, Luyong Wang, Yuelan Yin, Xin'an Jiao

{"title":"Dual glycosylation of wall teichoic acid modulates the O-antigen pattern and virulence in serovar 4b Listeria monocytogenes.","authors":"Hao Yao, Yuting Wang, Ruochen Wang, Zhengnan Dong, Zhenhua Wu, Luyong Wang, Yuelan Yin, Xin'an Jiao","doi":"10.1002/mlf2.70041","DOIUrl":"10.1002/mlf2.70041","url":null,"abstract":"Among the 14 serovars of Listeria monocytogenes (Lm), serovar 4b strains are the most predominant isolates linked to human listeriosis outbreaks-a phenotype associated with their unique wall teichoic acid (WTA) decorated with galactose (Gal) and glucose (Glu). A wealth of knowledge is available for galactosylated-WTA (Gal-WTA) manipulating bacterial homeostasis and virulence, whereas the relationship between glucosylated-WTA (Glu-WTA) and Gal-WTA in listerial physiology and pathogenesis remains unclear. Here, we find that Glu-WTA and Gal-WTA jointly constitute the O-antigen pattern of serovar 4b Lm; however, Glu-WTA specifically serves as the indispensable ligand for listeriophage LP4 adsorption. Moreover, the co-operation between Glu- and Gal-WTA increases biofilm formation and bacterial resistance to cationic antimicrobial peptide (CRAMP). We further demonstrate that Gal-WTA modulates the anchoring of surface proteins, including IspC, Ami, and InlB. Additionally, dual glycosylated WTA interaction with ActA facilitates bacterial intracellular motility and dissemination. Consistently, Glu-WTA significantly enhances bacterial colonization ability in the mesenteric lymph nodes (MLNs), ileum, liver, and brain of mouse, cooperating with Gal-WTA to facilitate Lm dissemination to distant organs and tissues. In conclusion, we reveal the crucial roles of Glu-WTA in synergizing with Gal-WTA to modulate the integrity of the cell wall structure and exacerbate bacterial infection, providing a global understanding of the hypervirulence and pathogenicity of invasive serovar 4b Lm.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"4 6","pages":"640-652"},"PeriodicalIF":6.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890751","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

Engineered AcrIIA5 for optogenetic control of CRISPR-Cas9-based genome editing. 基于crispr - cas9的基因组编辑的光遗传控制

IF 6.7

mLife Pub Date : 2025-12-12 eCollection Date: 2025-12-01 DOI: 10.1002/mlf2.70016

Qi Chen, Jia Yao, Yingfan Lu, Ruikang Qiu, Zixin Deng, Yuhui Sun

{"title":"Engineered AcrIIA5 for optogenetic control of CRISPR-Cas9-based genome editing.","authors":"Qi Chen, Jia Yao, Yingfan Lu, Ruikang Qiu, Zixin Deng, Yuhui Sun","doi":"10.1002/mlf2.70016","DOIUrl":"10.1002/mlf2.70016","url":null,"abstract":"The CRISPR-Cas9 system has been proven to be a powerful tool for gene editing in living cells and shows great potential in genetic disease treatment. Anti-CRISPR (Acr)-based optogenetic tools could spatiotemporally regulate the activity of CRISPR-Cas9, thereby improving the precision and safety of gene editing. However, these tools could only regulate a certain Cas9 protein because of the high specificity of Acr used, limiting their further application. In this study, we developed a new optogenetic tool named CASANOVA-A5 (CRISPR-Cas9 activity switching via a novel optogenetic variant of AcrIIA5) by inserting the blue light sensor AsLOV2 into AcrIIA5 with a broad inhibition spectrum. We proved that the CASANOVA-A5 could regulate the gene editing activity of SpCas9, SaCas9, NmeCas9, and St1Cas9 in a blue light-dependent manner. Additionally, we engineered AcrIIA5-LOV9 by integrating the blue light-dependent degron module LOV9, showing obvious optical regulation for SpCas9. Together, our work demonstrates two feasible methods to engineer the Acrs to potent optogenetic tools and suggests systematic strategies for further optimization.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"4 6","pages":"697-708"},"PeriodicalIF":6.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890749","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

Community-level wastewater surveillance with machine learning methods to assess underreporting of COVID-19 case counts. 利用机器学习方法对社区废水进行监测，以评估COVID-19病例数漏报情况。

IF 6.7

mLife Pub Date : 2025-12-03 eCollection Date: 2025-12-01 DOI: 10.1002/mlf2.70055

Nathan Szeto, Jianfeng Wu, Yili Wang, Xin Li, Zheshi Zheng, Leyao Zhang, Richard Neitzel, Marisa Eisenberg, J Tim Dvonch, Alfred Franzblau, Peter X K Song, Chuanwu Xi

引用次数: 0

Salinization influences the biodiversity-ecosystem functioning relationship more strongly at high salinity. 高盐度环境下，盐渍化对生物多样性与生态系统功能关系的影响更大。

IF 6.7

mLife Pub Date : 2025-11-18 eCollection Date: 2025-12-01 DOI: 10.1002/mlf2.70034

Jianrong Huang, Mingxian Han, Jian Yang, Yi Wang, Hongchen Jiang

{"title":"Salinization influences the biodiversity-ecosystem functioning relationship more strongly at high salinity.","authors":"Jianrong Huang, Mingxian Han, Jian Yang, Yi Wang, Hongchen Jiang","doi":"10.1002/mlf2.70034","DOIUrl":"10.1002/mlf2.70034","url":null,"abstract":"Salinization threatens ecosystem stability by altering microbial diversity and function, yet how salinity influences biodiversity-ecosystem functioning (BEF) relationships remains unclear. In this study, we constructed artificial microbial communities (5-40 strains) with varying salt tolerance and phylogeny, culturing them across a salinity gradient (0.9%-20%). We found that low-to-moderate salinity (0.9%-7%) minimally affected BEF relationships, but high salinity (15%-20%) amplified biodiversity loss impacts, with ecosystem yield declining sharply at low richness (R 2 = 0.573, p < 0.001). Hypersaline conditions shifted community composition toward halophiles (e.g., Halomonas dominance at 20% salinity) and inhibited metabolic functions, such as glycosyl hydrolase activity. Mechanistically, selection effects predominated at 15% salinity (contributing 63.1%-72.0% to net biodiversity effects), whereas complementarity effects were diminished. These findings underscore the vital role of biodiversity in mitigating hypersaline stress and highlight the necessity for targeted strategies to enhance ecosystem resilience against global salinization.","PeriodicalId":94145,"journal":{"name":"mLife","volume":"4 6","pages":"683-696"},"PeriodicalIF":6.7,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890727","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

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