Communications Biology最新文献_第4页

SARS-CoV-2 ORF3a accessory protein is a water-permeable channel that induces lysosome swelling.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-04 DOI: 10.1038/s42003-024-07442-5

Antonio Michelucci, Luigi Sforna, Riccardo Focaia, Maria Vittoria Leonardi, Angela Di Battista, Giorgia Rastelli, Simone Vespa, Simona Boncompagni, Manlio Di Cristina, Luigi Catacuzzeno

{"title":"SARS-CoV-2 ORF3a accessory protein is a water-permeable channel that induces lysosome swelling.","authors":"Antonio Michelucci, Luigi Sforna, Riccardo Focaia, Maria Vittoria Leonardi, Angela Di Battista, Giorgia Rastelli, Simone Vespa, Simona Boncompagni, Manlio Di Cristina, Luigi Catacuzzeno","doi":"10.1038/s42003-024-07442-5","DOIUrl":"10.1038/s42003-024-07442-5","url":null,"abstract":"ORF3a, the most abundantly expressed accessory protein of SARS-CoV-2, plays an essential role in virus egress by inactivating lysosomes through their deacidification. However, the mechanism underlying this process remains unclear. While seminal studies suggested ORF3a being a cation-selective channel (i.e., viroporin), recent works disproved this conclusion. To unravel the potential function of ORF3a, here we employed a multidisciplinary approach including patch-clamp electrophysiology, videoimaging, molecular dynamics (MD) simulations, and electron microscopy. Preliminary structural analyses and patch-clamp recordings in HEK293 cells rule out ORF3a functioning as either viroporin or proton (H+) channel. Conversely, videoimaging experiments demonstrate that ORF3a mediates the transmembrane transport of water. MD simulations identify the tetrameric assembly of ORF3a as the functional water transporter, with a putative selectivity filter for water permeation that includes two essential asparagines, N82 and N119. Consistent with this, N82L and N82W mutations abolish ORF3a-mediated water permeation. Finally, ORF3a expression in HEK293 cells leads to lysosomal volume increase, mitochondrial damage, and accumulation of intracellular membranes, all alterations reverted by the N82W mutation. We propose a novel function for ORF3a as a lysosomal water-permeable channel, essential for lysosome deacidification and inactivation, key steps to promote virus egress.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"170"},"PeriodicalIF":5.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering a promiscuous prenyltransferase for selective biosynthesis of an undescribed bioactive cannabinoid analog. 设计一种杂合前酰转移酶，以选择性地生物合成一种未被描述的生物活性大麻素类似物。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-04 DOI: 10.1038/s42003-025-07509-x

Qin Yan, Yue-Gui Chen, Xiao-Wen Yang, An Wang, Xiao-Ping He, Xue Tang, Hong Hu, Kai Guo, Zong-Hua Xiao, Yan Liu, Sheng-Hong Li

{"title":"Engineering a promiscuous prenyltransferase for selective biosynthesis of an undescribed bioactive cannabinoid analog.","authors":"Qin Yan, Yue-Gui Chen, Xiao-Wen Yang, An Wang, Xiao-Ping He, Xue Tang, Hong Hu, Kai Guo, Zong-Hua Xiao, Yan Liu, Sheng-Hong Li","doi":"10.1038/s42003-025-07509-x","DOIUrl":"10.1038/s42003-025-07509-x","url":null,"abstract":"Cannabinoids are unique meroterpenoids, with cannabigerolic acid (CBGA) serving as a dedicated precursor. This study introduces a fungal aromatic prenyltransferase AscC into the engineered Escherichia coli to catalyze the transfer of C5-C15 terpenoid linear precursors to olivetolic acid. Four CBGA derivatives (compounds 1-4) with diverse C5, C10, or C15 prenyl chains are isolated and identified, with compound 4 being an undescribed product featuring a C15 prenyl chain at the C-5 position. Compound 4 demonstrates the highest anti-neuroinflammatory and antibacterial activities, with IC50 values of 3.06 µM for TNF-α and 4.31 µM for IL-6, alongside EC50 values ranging from 0.87 to 3.16 µM against three Gram-positive bacteria. An efficient construct is established by incorporating an additional copy of AscC, resulting in a yield of 14.85 ± 0.91 mg/L of compound 4. Two mutants, L180Y and L180F, are engineered to selectively produce compound 4. These findings provide a foundation for enriching the chemical diversity of bioactive cannabinoid analogs with various prenyl moieties through combinatorial biosynthesis.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"173"},"PeriodicalIF":5.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The diversity and applications of microbial iron metabolism and iron-containing proteins.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-04 DOI: 10.1038/s42003-024-07373-1

Haichun Gao, Ingrid Span

引用次数: 0

Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy. 在人类尿路感染过程中，噬菌体与细菌病原体的合作支持溶菌噬菌体疗法。

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-04 DOI: 10.1038/s42003-025-07598-8

Mahmood Almosuli, Anna Kirtava, Archil Chkhotua, Lia Tsveniashvili, Nina Chanishvili, Sumaiya Safia Irfan, Emily Ng, Hope McIntyre, Adam J Hockenberry, Robyn P Araujo, Weidong Zhou, Ngoc Vuong, Barbara Birkaya, Lance Liotta, Alessandra Luchini

{"title":"Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy.","authors":"Mahmood Almosuli, Anna Kirtava, Archil Chkhotua, Lia Tsveniashvili, Nina Chanishvili, Sumaiya Safia Irfan, Emily Ng, Hope McIntyre, Adam J Hockenberry, Robyn P Araujo, Weidong Zhou, Ngoc Vuong, Barbara Birkaya, Lance Liotta, Alessandra Luchini","doi":"10.1038/s42003-025-07598-8","DOIUrl":"10.1038/s42003-025-07598-8","url":null,"abstract":"Despite much promise in overcoming drug-resistant infections, clinical studies of bacteriophage antibacterial therapy have failed to show durable effectiveness. Although lysogeny plays an important role in bacterial physiology, its significance in diverse microbiomes remains unclear. Here, we tested the following hypotheses: 1) urinary microbiome phage populations switch to a higher relative proportion of temperate phages, and 2) the activity of the phage recombination machinery (integration/excision/transposition) is higher during human urinary tract infections (UTIs) than in non-infected urinary tracts. Using human urine, model organisms, mass spectrometry, gene expression analysis, and the phage phenotype prediction model BACPHLIP, the results corroborated our hypotheses at the functional protein and gene levels. From a human health perspective, these data suggest that temperate phages may facilitate bacterial infections rather than function as protective agents. These findings support the use of lysogenic phages as therapeutic Trojan Horses.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"175"},"PeriodicalIF":5.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prolonged exposure to heat enhances mosquito tolerance to viral infection.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-04 DOI: 10.1038/s42003-025-07617-8

Hugo D Perdomo, Ayda Khorramnejad, Nfamara M Cham, Alida Kropf, Davide Sogliani, Mariangela Bonizzoni

引用次数: 0

Identification of selective SWI/SNF dependencies in enzalutamide-resistant prostate cancer.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-04 DOI: 10.1038/s42003-024-07413-w

Bengul Gokbayrak, Umut Berkay Altintas, Shreyas Lingadahalli, Tunc Morova, Chia-Chi Flora Huang, Betul Ersoy Fazlioglu, Ivan Pak Lok Yu, Batuhan M Kalkan, Paloma Cejas, Sonia H Y Kung, Ladan Fazli, Akane Kawamura, Henry W Long, Ceyda Acilan, Tamer T Onder, Tugba Bagci-Onder, James T Lynch, Nathan A Lack

{"title":"Identification of selective SWI/SNF dependencies in enzalutamide-resistant prostate cancer.","authors":"Bengul Gokbayrak, Umut Berkay Altintas, Shreyas Lingadahalli, Tunc Morova, Chia-Chi Flora Huang, Betul Ersoy Fazlioglu, Ivan Pak Lok Yu, Batuhan M Kalkan, Paloma Cejas, Sonia H Y Kung, Ladan Fazli, Akane Kawamura, Henry W Long, Ceyda Acilan, Tamer T Onder, Tugba Bagci-Onder, James T Lynch, Nathan A Lack","doi":"10.1038/s42003-024-07413-w","DOIUrl":"10.1038/s42003-024-07413-w","url":null,"abstract":"Enzalutamide is a potent second-generation antiandrogen commonly used to treat hormone-sensitive and castration-resistant prostate cancer (CRPC) patients. While initially effective, the disease almost always develops resistance. Given that many enzalutamide-resistant tumors lack specific somatic mutations, there is strong evidence that epigenetic factors can cause enzalutamide resistance. To explore how resistance arises, we systematically test all epigenetic modifiers in several models of castration-resistant and enzalutamide-resistant prostate cancer with a custom epigenetic CRISPR library. From this, we identify and validate SMARCC2, a core component of the SWI/SNF complex, that is selectivity essential in enzalutamide-resistant models. We show that the chromatin occupancy of SMARCC2 and BRG1 is expanded in enzalutamide resistance at regions that overlap with CRPC-associated transcription factors that are accessible in CRPC clinical samples. Overall, our study reveals a regulatory role for SMARCC2 in enzalutamide-resistant prostate cancer and supports the feasibility of targeting the SWI/SNF complex in late-stage PCa.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"169"},"PeriodicalIF":5.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Micromechanical behavior of the apple fruit cuticle investigated by Brillouin light scattering microscopy.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-04 DOI: 10.1038/s42003-025-07555-5

Timm Landes, Bishnu P Khanal, Hans Lukas Bethge, Tina Lehrich, Maximilian Seydi Kilic, Franz Renz, Miroslav Zabic, Moritz Knoche, Dag Heinemann

{"title":"Micromechanical behavior of the apple fruit cuticle investigated by Brillouin light scattering microscopy.","authors":"Timm Landes, Bishnu P Khanal, Hans Lukas Bethge, Tina Lehrich, Maximilian Seydi Kilic, Franz Renz, Miroslav Zabic, Moritz Knoche, Dag Heinemann","doi":"10.1038/s42003-025-07555-5","DOIUrl":"10.1038/s42003-025-07555-5","url":null,"abstract":"The cuticle is a polymeric membrane covering all plant aerial organs of primary origin. It regulates water loss and defends against environmental stressors and pathogens. Despite its significance, understanding of the micro-mechanical properties of the cuticle (cuticular membrane; CM) remains limited. In this study, non-invasive Brillouin light scattering (BLS) spectroscopy was applied to probe the micro-mechanics of native CM, dewaxed CM (DCM), and isolated cutin matrix (CU) of mature apple fruit. The BLS signal arises from the photon interaction with thermally induced pressure waves and allows for imaging with mechanical contrast. The derived loss tangent showed significant differences with wax extraction from the CM and further with carbohydrate extraction from the DCM, consistent with tensile test results. Spatial heterogeneity between anticlinal and periclinal regions was observed by BLS microscopy of CM and DCM, but not in CU. The key conclusions are: (1) BLS is sensitive to micro-mechanical variations, particularly the strain-stiffening effect of the cutin framework, offering insights into the CM's micro-mechanical behavior and underlying chemical structures; (2) CM and DCM exhibit spatial micro-mechanical heterogeneity between periclinal and anticlinal regions.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"174"},"PeriodicalIF":5.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-04 DOI: 10.1038/s42003-025-07621-y

Yangyang Fu, Shishun Huang, Rulu Pan, Xingan Chen, Ting Liu, Rongzhe Zhang, Fangsheng Zhu, Qiwei Fang, Liyue Wu, Juji Dai, Ouchen Wang, Liting Lu, Xiduan Wei, Liangxing Wang, Xincheng Lu

{"title":"The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling.","authors":"Yangyang Fu, Shishun Huang, Rulu Pan, Xingan Chen, Ting Liu, Rongzhe Zhang, Fangsheng Zhu, Qiwei Fang, Liyue Wu, Juji Dai, Ouchen Wang, Liting Lu, Xiduan Wei, Liangxing Wang, Xincheng Lu","doi":"10.1038/s42003-025-07621-y","DOIUrl":"10.1038/s42003-025-07621-y","url":null,"abstract":"Phosphodiesterase 4D interacting protein (PDE4DIP) is a Golgi/centrosome-associated protein that plays critical roles in the regulation of microtubule dynamics and maintenance of the Golgi structure. However, its biological role in human cancer remains largely unknown. In this study, we showed that PDE4DIP is overexpressed in human non-small cell lung cancer (NSCLC) tissues and that upregulated PDE4DIP expression is associated with poor prognosis in patients with lung cancer. We demonstrated that PDE4DIP knockdown inhibits NSCLC cell proliferation in vitro and tumorigenicity in vivo. We further demonstrated that PDE4DIP knockdown triggers apoptosis and cell cycle arrest in NSCLC cells by activating the Protein kinase A (PKA) /CREB signalling pathway. PDE4DIP coordinates with A-kinase anchoring proteins 9 (AKAP9) to enhance the Golgi localization and stability of PKA RIIα. Depletion of PDE4DIP mislocalizes PKA RIIα from the Golgi and leads to its degradation, thereby compromising its negative regulatory effect on PKA signalling. Overall, our findings provide novel insights into the roles of the PDE4DIP-AKAP9 complex in regulating PKA signalling and NSCLC growth and highlight PDE4DIP as a promising therapeutic target for NSCLC.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"178"},"PeriodicalIF":5.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prediction of hemolytic peptides and their hemolytic concentration.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-04 DOI: 10.1038/s42003-025-07615-w

Anand Singh Rathore, Nishant Kumar, Shubham Choudhury, Naman Kumar Mehta, Gajendra P S Raghava

{"title":"Prediction of hemolytic peptides and their hemolytic concentration.","authors":"Anand Singh Rathore, Nishant Kumar, Shubham Choudhury, Naman Kumar Mehta, Gajendra P S Raghava","doi":"10.1038/s42003-025-07615-w","DOIUrl":"10.1038/s42003-025-07615-w","url":null,"abstract":"Peptide-based drugs often fail in clinical trials due to their toxicity or hemolytic activity against red blood cells (RBCs). Existing methods predict hemolytic peptides but not the concentration (HC50) required to lyse 50% of RBCs. This study develops classification and regression models to identify and quantify hemolytic activity. These models train on 1926 peptides with experimentally determined HC50 against mammalian RBCs. Analysis indicates that hydrophobic and positively charged residues were associated with higher hemolytic activity. Among classification models, including machine learning (ML), quantum ML, and protein language models, a hybrid model combining random forest (RF) and a motif-based approach achieves the highest area under the receiver operating characteristic curve (AUROC) of 0.921. Regression models achieve a Pearson correlation coefficient (R) of 0.739 and a coefficient of determination (R²) of 0.543. These models outperform existing methods and are implemented in HemoPI2, a web-based platform and standalone software for designing peptides with desired HC50 values ( http://webs.iiitd.edu.in/raghava/hemopi2/ ).","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"176"},"PeriodicalIF":5.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of metabolism, resistance, and/or antagonism as drivers of endomicrobiomes assemblage in Origanum heracleoticum L.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07527-9

Giulia Semenzato, Francesco Vitali, Arcangela Frascella, Ludovica Lollini, Stefano Mocali, Alessio Papini, Renato Fani, Giovanni Emiliani

{"title":"Role of metabolism, resistance, and/or antagonism as drivers of endomicrobiomes assemblage in Origanum heracleoticum L.","authors":"Giulia Semenzato, Francesco Vitali, Arcangela Frascella, Ludovica Lollini, Stefano Mocali, Alessio Papini, Renato Fani, Giovanni Emiliani","doi":"10.1038/s42003-025-07527-9","DOIUrl":"10.1038/s42003-025-07527-9","url":null,"abstract":"The understanding of selective forces driving the compartmentalization of microbiota in plants remains limited. In this study, we performed a phenotypic characterization of bacterial endophytes isolated from the medicinal plant Origanum heracleoticum, together with the determination of the antibiotic resistance profiles and the antagonistic interactions of communities within and across different plant organs. Results revealed organ-related differences in the metabolic capabilities of bacteria, with those associated with stems displaying the highest metabolic activity for carbon sources. Contrarily, the patterns of antibiotic resistance appeared closely aligned with the taxonomical classification of the endophytes. The presence of antagonistic interactions, likely spurred by resource limitations, favor bacteria exhibiting greater metabolic plasticity. In conclusion, this research advances our comprehension of the intricate dynamics between plants and their associated microbiota, indicating that its composition is mainly influenced by forces contributing to the selection of distinct functions and phenotypic traits.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"158"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0