Drug Resistance Updates最新文献

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Un-methylation of NUDT21 represses docosahexaenoic acid biosynthesis contributing to enzalutamide resistance in prostate cancer NUDT21 的非甲基化抑制了二十二碳六烯酸的生物合成,导致前列腺癌对恩杂鲁胺产生耐药性
IF 15.8 1区 医学
Drug Resistance Updates Pub Date : 2024-08-24 DOI: 10.1016/j.drup.2024.101144
Shin-Chih Lin , Ya-Chuan Tsai , Ying-Lan Chen , Hui-Kuan Lin , Yun-Chen Huang , Yi-Syuan Lin , Yu-Sheng Cheng , Hsing-Yi Chen , Chia-Jung Li , Tsung-Yen Lin , Shih-Chieh Lin
{"title":"Un-methylation of NUDT21 represses docosahexaenoic acid biosynthesis contributing to enzalutamide resistance in prostate cancer","authors":"Shin-Chih Lin ,&nbsp;Ya-Chuan Tsai ,&nbsp;Ying-Lan Chen ,&nbsp;Hui-Kuan Lin ,&nbsp;Yun-Chen Huang ,&nbsp;Yi-Syuan Lin ,&nbsp;Yu-Sheng Cheng ,&nbsp;Hsing-Yi Chen ,&nbsp;Chia-Jung Li ,&nbsp;Tsung-Yen Lin ,&nbsp;Shih-Chieh Lin","doi":"10.1016/j.drup.2024.101144","DOIUrl":"10.1016/j.drup.2024.101144","url":null,"abstract":"<div><h3>Aims</h3><p>The recent approval of enzalutamide for metastatic castration-sensitive prostate cancer underscores its growing clinical significance, raising concerns about emerging resistance and limited treatment options. While the reactivation of the androgen receptor (AR) and other genes plays a role in enzalutamide resistance, identifications of novel underlying mechanism with therapeutic potential in enzalutamide-resistant (EnzaR) cells remain largely elusive.</p></div><div><h3>Methods</h3><p>Drug-resistant prostate cancer cell lines, animal models, and organoids were utilized to examine NUDT21 function by transcriptomic and metabolomic analyses through loss-of-function and gain-of-function assays. Notably, a mono-methylation monoclonal antibody and conditional-knockin transgenic mouse model of NUDT21 were generated for evaluating its function.</p></div><div><h3>Results</h3><p>NUDT21 overexpression acts as a crucial alternative polyadenylation (APA) mediator, supported by its oncogenic role in prostate cancer. PRMT7-mediated mono-methylation of NUDT21 induces a shift in 3’UTR usage, reducing oncogenicity. In contrast, its un-methylation promotes cancer growth and cuproptosis insensitivity in EnzaR cells by exporting toxic copper and suppressing docosahexaenoic acid (DHA) biosynthesis. Crucially, NUDT21 inhibition or DHA supplementation with copper ionophore holds therapeutic promise for EnzaR cells.</p></div><div><h3>Conclusions</h3><p>The un-methylation of NUDT21-mediated 3’UTR shortening unveils a novel mechanism for enzalutamide resistance, and our findings offer innovative strategies for advancing the treatment of prostate cancer patients experiencing enzalutamide resistance.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101144"},"PeriodicalIF":15.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S136876462400102X/pdfft?md5=8d5415fa3df7d10f5e75ab1ffb7c812f&pid=1-s2.0-S136876462400102X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRISPR-AMRtracker: A novel toolkit to monitor the antimicrobial resistance gene transfer in fecal microbiota CRISPR-AMRtracker:监测粪便微生物群中抗菌药耐药性基因转移的新型工具包
IF 15.8 1区 医学
Drug Resistance Updates Pub Date : 2024-08-24 DOI: 10.1016/j.drup.2024.101142
Gong Li , Teng-Fei Long , Shi-Ying Zhou , Li-Juan Xia , Ang Gao , Lei Wan , Xiao-Yuan Diao , Yu-Zhang He , Ruan-Yang Sun , Jin-Tao Yang , Sheng-Qiu Tang , Hao Ren , Liang-Xing Fang , Xiao-Ping Liao , Ya-Hong Liu , Liang Chen , Jian Sun
{"title":"CRISPR-AMRtracker: A novel toolkit to monitor the antimicrobial resistance gene transfer in fecal microbiota","authors":"Gong Li ,&nbsp;Teng-Fei Long ,&nbsp;Shi-Ying Zhou ,&nbsp;Li-Juan Xia ,&nbsp;Ang Gao ,&nbsp;Lei Wan ,&nbsp;Xiao-Yuan Diao ,&nbsp;Yu-Zhang He ,&nbsp;Ruan-Yang Sun ,&nbsp;Jin-Tao Yang ,&nbsp;Sheng-Qiu Tang ,&nbsp;Hao Ren ,&nbsp;Liang-Xing Fang ,&nbsp;Xiao-Ping Liao ,&nbsp;Ya-Hong Liu ,&nbsp;Liang Chen ,&nbsp;Jian Sun","doi":"10.1016/j.drup.2024.101142","DOIUrl":"10.1016/j.drup.2024.101142","url":null,"abstract":"<div><p>The spread of antibiotic resistance genes (ARGs), particularly those carried on plasmids, poses a major risk to global health. However, the extent and frequency of ARGs transfer in microbial communities among human, animal, and environmental sectors is not well understood due to a lack of effective tracking tools. We have developed a novel fluorescent tracing tool, CRISPR-AMRtracker, to study ARG transfer. It combines CRISPR/Cas9 fluorescence tagging, fluorescence-activated cell sorting, 16S rRNA gene sequencing, and microbial community analysis. CRISPR-AMRtracker integrates a fluorescent tag immediately downstream of ARGs, enabling the tracking of ARG transfer without compromising the host cell's antibiotic susceptibility, fitness, conjugation, and transposition. Notably, our experiments demonstrate that <em>sfGFP</em>-tagged plasmid-borne <em>mcr-1</em> can transfer across diverse bacterial species within fecal samples. This innovative approach holds the potential to illuminate the dynamics of ARG dissemination and provide valuable insights to shape effective strategies in mitigating the escalating threat of antibiotic resistance.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101142"},"PeriodicalIF":15.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fusion event mediated by IS903B between chromosome and plasmid in two MCR-9- and KPC-2-co-producing Klebsiella pneumoniae isolates 由 IS903B 介导的两种 MCR-9 和 KPC-2 共同产生的肺炎克雷伯菌分离株染色体与质粒之间的融合事件
IF 15.8 1区 医学
Drug Resistance Updates Pub Date : 2024-08-17 DOI: 10.1016/j.drup.2024.101139
Ruishan Liu , Yingying Chen , Hao Xu , Huanran Zhang , Yi Liu , Xiaojing Liu , Haowei Ye , Mantao Chen , Beiwen Zheng
{"title":"Fusion event mediated by IS903B between chromosome and plasmid in two MCR-9- and KPC-2-co-producing Klebsiella pneumoniae isolates","authors":"Ruishan Liu ,&nbsp;Yingying Chen ,&nbsp;Hao Xu ,&nbsp;Huanran Zhang ,&nbsp;Yi Liu ,&nbsp;Xiaojing Liu ,&nbsp;Haowei Ye ,&nbsp;Mantao Chen ,&nbsp;Beiwen Zheng","doi":"10.1016/j.drup.2024.101139","DOIUrl":"10.1016/j.drup.2024.101139","url":null,"abstract":"<div><p>Herein, we first isolated two MCR-9- and KPC-2-co-producing <em>K. pneumoniae</em> isolates. Notably, we observed a fusion event between the chromosome and plasmid, mediated by IS<em>903B</em>, in these two strains. This cointegration of chromosomes and plasmids introduces a new mode of transmission for antimicrobial resistance genes.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101139"},"PeriodicalIF":15.8,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling the secrets: Evolution of resistance mediated by membrane proteins 揭开秘密膜蛋白介导的抗药性进化
IF 15.8 1区 医学
Drug Resistance Updates Pub Date : 2024-08-16 DOI: 10.1016/j.drup.2024.101140
Xue Yang , Min Li , Zi-Chang Jia , Yan Liu , Shun-Fan Wu , Mo-Xian Chen , Ge-Fei Hao , Qing Yang
{"title":"Unraveling the secrets: Evolution of resistance mediated by membrane proteins","authors":"Xue Yang ,&nbsp;Min Li ,&nbsp;Zi-Chang Jia ,&nbsp;Yan Liu ,&nbsp;Shun-Fan Wu ,&nbsp;Mo-Xian Chen ,&nbsp;Ge-Fei Hao ,&nbsp;Qing Yang","doi":"10.1016/j.drup.2024.101140","DOIUrl":"10.1016/j.drup.2024.101140","url":null,"abstract":"<div><p>Membrane protein-mediated resistance is a multidisciplinary challenge that spans fields such as medicine, agriculture, and environmental science. Understanding its complexity and devising innovative strategies are crucial for treating diseases like cancer and managing resistant pests in agriculture. This paper explores the dual nature of resistance mechanisms across different organisms: On one hand, animals, bacteria, fungi, plants, and insects exhibit convergent evolution, leading to the development of similar resistance mechanisms. On the other hand, influenced by diverse environmental pressures and structural differences among organisms, they also demonstrate divergent resistance characteristics. Membrane protein-mediated resistance mechanisms are prevalent across animals, bacteria, fungi, plants, and insects, reflecting their shared survival strategies evolved through convergent evolution to address similar survival challenges. However, variations in ecological environments and biological characteristics result in differing responses to resistance. Therefore, examining these differences not only enhances our understanding of adaptive resistance mechanisms but also provides crucial theoretical support and insights for addressing drug resistance and advancing pharmaceutical development.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101140"},"PeriodicalIF":15.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764624000980/pdfft?md5=f32ad03042bf67bda91992e6b1153808&pid=1-s2.0-S1368764624000980-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142148766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae 促进肺炎链球菌获得大环内酯耐药性的决定因素的超微结构、代谢和遗传特征
IF 15.8 1区 医学
Drug Resistance Updates Pub Date : 2024-08-16 DOI: 10.1016/j.drup.2024.101138
Xueqing Wu , Babek Alibayov , Xi Xiang , Santiago M. Lattar , Fuminori Sakai , Austin A. Medders , Brenda S. Antezana , Lance E. Keller , Ana G.J. Vidal , Yih-Ling Tzeng , D. Ashley Robinson , David S. Stephens , Yunsong Yu , Jorge E. Vidal
{"title":"Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae","authors":"Xueqing Wu ,&nbsp;Babek Alibayov ,&nbsp;Xi Xiang ,&nbsp;Santiago M. Lattar ,&nbsp;Fuminori Sakai ,&nbsp;Austin A. Medders ,&nbsp;Brenda S. Antezana ,&nbsp;Lance E. Keller ,&nbsp;Ana G.J. Vidal ,&nbsp;Yih-Ling Tzeng ,&nbsp;D. Ashley Robinson ,&nbsp;David S. Stephens ,&nbsp;Yunsong Yu ,&nbsp;Jorge E. Vidal","doi":"10.1016/j.drup.2024.101138","DOIUrl":"10.1016/j.drup.2024.101138","url":null,"abstract":"<div><h3>Aims</h3><p>To investigate the molecular events associated with acquiring macrolide resistance genes [<em>mefE</em>/<em>mel</em> (Mega) or <em>ermB</em>] in <em>Streptococcus pneumoniae</em> (<em>Spn</em>) during nasopharyngeal colonization.</p></div><div><h3>Methods and results</h3><p>Genomic analysis of 128 macrolide-resistant <em>Spn</em> isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn<em>916</em>-related elements. Studies using confocal and electron microscopy demonstrated that during the transfer of Tn<em>916</em>-related elements in nasopharyngeal cell biofilms, pneumococcal strains formed clusters facilitating their acquisition of resistance determinants at a high recombination frequency (rF). Remarkably, these aggregates comprise both encapsulated and nonencapsulated pneumococci that span extracellular and intracellular compartments. rF assessments showed similar rates regardless Mega was associated with large integrative and conjugative elements (ICEs) (&gt;23 kb) or not (∼5.4 kb). The rF for Mega Class IV(c) insertion region (∼53 kb) was three orders of magnitude higher than the transformation of the capsule locus. Metabolomics studies of the microenvironment created by colonization of human nasopharyngeal cells revealed a link between the acquisition of ICEs and the pathways involving nicotinic acid and sucrose.</p></div><div><h3>Conclusions</h3><p>Pneumococcal clusters, both extracellular and intracellular, facilitate macrolide resistance acquisition, and ICEs were acquired at a higher frequency than the capsule locus. Metabolic changes could serve as intervention targets.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101138"},"PeriodicalIF":15.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Folylpolyglutamate synthetase inactivation in relapsed ALL induces a druggable folate metabolic vulnerability 复发 ALL 中的 Folylpolyglutamate synthetase 失活会诱发可服药的叶酸代谢脆弱性
IF 15.8 1区 医学
Drug Resistance Updates Pub Date : 2024-08-16 DOI: 10.1016/j.drup.2024.101141
Hui Li , Yao Chen , Ming Ding , Jingjing Liu , Huiying Sun , Houshun Fang , Samuel W. Brady , Yan Xu , Fabian Glaser , Xiaotu Ma , Yabin Tang , Liang Du , Xiaoyu Wu , Shuxuan Wang , Liang Zhu , Benshang Li , Shuhong Shen , Jinghui Zhang , Liang Zheng , Jiyang Yu , Bin-Bing S. Zhou
{"title":"Folylpolyglutamate synthetase inactivation in relapsed ALL induces a druggable folate metabolic vulnerability","authors":"Hui Li ,&nbsp;Yao Chen ,&nbsp;Ming Ding ,&nbsp;Jingjing Liu ,&nbsp;Huiying Sun ,&nbsp;Houshun Fang ,&nbsp;Samuel W. Brady ,&nbsp;Yan Xu ,&nbsp;Fabian Glaser ,&nbsp;Xiaotu Ma ,&nbsp;Yabin Tang ,&nbsp;Liang Du ,&nbsp;Xiaoyu Wu ,&nbsp;Shuxuan Wang ,&nbsp;Liang Zhu ,&nbsp;Benshang Li ,&nbsp;Shuhong Shen ,&nbsp;Jinghui Zhang ,&nbsp;Liang Zheng ,&nbsp;Jiyang Yu ,&nbsp;Bin-Bing S. Zhou","doi":"10.1016/j.drup.2024.101141","DOIUrl":"10.1016/j.drup.2024.101141","url":null,"abstract":"<div><h3>Aims</h3><p>The antifolate methotrexate (MTX) is an anchor drug used in acute lymphoblastic leukemia (ALL) with poorly understood chemoresistance mechanisms in relapse. Herein we find decreased folate polyglutamylation network activities and inactivating <em>FPGS</em> mutations, both of which could induce MTX resistance and folate metabolic vulnerability in relapsed ALL.</p></div><div><h3>Methods</h3><p>We utilized integrated systems biology analysis of transcriptomic and genomic data from relapse ALL cohorts to infer hidden ALL relapse drivers and related genetic alternations during clonal evolution. The drug sensitivity assay was used to determine the impact of relapse-specific <em>FPGS</em> mutations on sensitivity to different antifolates and chemotherapeutics in ALL cells. We used liquid chromatography-mass spectrometry (LC-MS) to quantify MTX and folate polyglutamate levels in folylpoly-γ-glutamate synthetase (FPGS) mutant ALL cells. Enzymatic activity and protein degradation assays were also conducted to characterize the catalytic properties and protein stabilities of FPGS mutants. An ALL cell line-derived mouse leukemia xenograft model was used to evaluate the <em>in vivo</em> impact of <em>FPGS</em> inactivation on leukemogenesis and sensitivity to the polyglutamatable antifolate MTX as well as non-polyglutamatble lipophilic antifolate trimetrexate (TMQ).</p></div><div><h3>Results</h3><p>We found a significant decrease in folate polyglutamylation network activities during ALL relapse using RNA-seq data. Supported by functional evidence, we identified multifactorial mechanisms of <em>FPGS</em> inactivation in relapsed ALL, including its decreased network activity and gene expression, focal gene deletion, impaired catalytic activity, and increased protein degradation. These deleterious <em>FPGS</em> alterations induce MTX resistance and inevitably cause marked intracellular folate shrinkage, which could be efficiently targeted by a polyglutamylation-independent lipophilic antifolate TMQ <em>in vitro</em> and <em>in vivo</em>.</p></div><div><h3>Conclusions</h3><p>MTX resistance in relapsed ALL relies on <em>FPGS</em> inactivation, which inevitably induces a folate metabolic vulnerability, allowing for an efficacious antifolate ALL treatment strategy that is based upon TMQ, thereby surmounting chemoresistance in relapsed ALL.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101141"},"PeriodicalIF":15.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The key role of iroBCDN-lacking pLVPK-like plasmid in the evolution of the most prevalent hypervirulent carbapenem-resistant ST11-KL64 Klebsiella pneumoniae in China 缺乏 iroBCDN 的 pLVPK 样质粒在中国最流行的高病毒性碳青霉烯耐药 ST11-KL64 肺炎克雷伯菌进化中的关键作用
IF 15.8 1区 医学
Drug Resistance Updates Pub Date : 2024-08-14 DOI: 10.1016/j.drup.2024.101137
Xinmiao Jia , Ying Zhu , Peiyao Jia , Cuidan Li , Xiaobing Chu , Tianshu Sun , Xiaoyu Liu , Wei Yu , Fei Chen , Yingchun Xu , Qiwen Yang
{"title":"The key role of iroBCDN-lacking pLVPK-like plasmid in the evolution of the most prevalent hypervirulent carbapenem-resistant ST11-KL64 Klebsiella pneumoniae in China","authors":"Xinmiao Jia ,&nbsp;Ying Zhu ,&nbsp;Peiyao Jia ,&nbsp;Cuidan Li ,&nbsp;Xiaobing Chu ,&nbsp;Tianshu Sun ,&nbsp;Xiaoyu Liu ,&nbsp;Wei Yu ,&nbsp;Fei Chen ,&nbsp;Yingchun Xu ,&nbsp;Qiwen Yang","doi":"10.1016/j.drup.2024.101137","DOIUrl":"10.1016/j.drup.2024.101137","url":null,"abstract":"<div><h3>Aims</h3><p>Hypervirulent carbapenem-resistant <em>Klebsiella pneumoniae</em> (hv-CRKP), coharboring hypervirulence and carbapenem-resistance genes mediated by plasmids, causes infections with extremely high mortality and seriously impacts public health. Exploring the transfer mechanisms of virulence/carbapenem-resistance plasmids, as well as the formation and evolution pathway of hv-CRKP is of great significance to the control of hv-CRKP infections.</p></div><div><h3>Methods</h3><p>In this study, we identified the predominant clone of hv-CRKP in China and elucidated its genomic characteristics and formation route based on 239 multicenter clinical <em>K. pneumoniae</em> isolates and 1014 GenBank genomes by using comparative genomic analysis. Further, we revealed the factors affecting the transfer of virulence plasmids, and explained the genetic foundation for the prevalence of Chinese predominant hv-CRKP clone.</p></div><div><h3>Results</h3><p>ST11-KL64 is the predominant clone of hv-CRKP in China and primarily evolved from ST11-KL64 CRKP by acquiring the pLVPK-like virulence plasmid from hvKP. Significantly, the virulence gene cluster <em>iroBCDN</em> was lost in the virulence plasmid of ST11-KL64 hv-CRKP but existed in that of hvKP. Moreover, the absence of <em>iroBCDN</em> didn’t decrease the virulence of hv-CRKP, which was proved by bacterial test, cell-interaction test and mice infection model. On the contrary, loss of <em>iroBCDN</em> was observed to regulate virulence/carbapenem-resistance plasmid transfer and oxidative stress-related genes in strains and thus promoted the mobilization of nonconjugative virulence plasmid from hvKP into ST11-KL64 CRKP, forming hv-CRKP which finally had elevated antioxidant capacity and enhanced survival capacity in macrophages. The loss of <em>iroBCDN</em> increased the survival ability of hv-CRKP without decreasing its virulence, endowing it with an evolutionary advantage.</p></div><div><h3>Conclusions</h3><p>Our work provides new insights into the key role of <em>iroBCDN</em> loss in convergence of CRKP and hvKP, and the genetic and biological foundation for the widespread prevalence of ST11-KL64 hv-CRKP in China.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101137"},"PeriodicalIF":15.8,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764624000955/pdfft?md5=eabe17f35a7d1fc472d7ca2a4d2fd49b&pid=1-s2.0-S1368764624000955-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation CBX4 通过诱导 YAP1 SUMOylation 抵消细胞衰老,使胃癌细胞对化疗不再敏感
IF 15.8 1区 医学
Drug Resistance Updates Pub Date : 2024-08-12 DOI: 10.1016/j.drup.2024.101136
Yunru Gu , Tingting Xu , Yuan Fang , Jun Shao , Tong Hu , Xi Wu , Haoyang Shen , Yangyue Xu , Jingxin Zhang , Yu Song , Yang Xia , Yongqian Shu , Pei Ma
{"title":"CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation","authors":"Yunru Gu ,&nbsp;Tingting Xu ,&nbsp;Yuan Fang ,&nbsp;Jun Shao ,&nbsp;Tong Hu ,&nbsp;Xi Wu ,&nbsp;Haoyang Shen ,&nbsp;Yangyue Xu ,&nbsp;Jingxin Zhang ,&nbsp;Yu Song ,&nbsp;Yang Xia ,&nbsp;Yongqian Shu ,&nbsp;Pei Ma","doi":"10.1016/j.drup.2024.101136","DOIUrl":"10.1016/j.drup.2024.101136","url":null,"abstract":"<div><h3>Aims</h3><p>As our comprehension of the intricate relationship between cellular senescence and tumor biology continues to evolve, the therapeutic potential of cellular senescence is gaining increasing recognition. Here, we identify chromobox 4 (CBX4), a Small Ubiquitin-related Modifier (SUMO) E3 ligase, as an antagonist of cellular senescence and elucidate a novel mechanism by which CBX4 promotes drug resistance and malignant progression of gastric cancer (GC).</p></div><div><h3>Methods</h3><p><em>In vitro</em> and <em>in vivo</em> models were conducted to investigate the manifestation and impact of CBX4 on cellular senescence and chemoresistance. High-throughput sequencing, chromatin immunoprecipitation, and co-immunoprecipitation techniques were utilized to identify the upstream regulators and downstream effectors associated with CBX4, revealing its intricate regulatory network.</p></div><div><h3>Results</h3><p>CBX4 diminishes the sensitivity of GC cells to cellular senescence, facilitating chemoresistance and GC development by deactivating the senescence-related Hippo pathway. Mechanistically, low-dose cisplatin transcriptionally downregulates CBX4 through CEBPB. In addition, CBX4 preserves the stability and cytoplasm-nuclear transport of YAP1, the key player of Hippo pathway, by inducing SUMO1 modification at K97 and K280, which competitively inhibits YAP1-S127 phosphorylation.</p></div><div><h3>Conclusions</h3><p>Our study highlights the anti-senescence role of CBX4 and suggests that CBX4 inhibition in combination with low-dose cisplatin has the potential to overcome chemoresistance and effectively restrict GC progression.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101136"},"PeriodicalIF":15.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial: ABC transporters and drug resistance 社论:ABC 转运体与耐药性
IF 15.8 1区 医学
Drug Resistance Updates Pub Date : 2024-08-10 DOI: 10.1016/j.drup.2024.101135
Qisi Lu, Suresh V. Ambudkar, Dong-Hua Yang
{"title":"Editorial: ABC transporters and drug resistance","authors":"Qisi Lu,&nbsp;Suresh V. Ambudkar,&nbsp;Dong-Hua Yang","doi":"10.1016/j.drup.2024.101135","DOIUrl":"10.1016/j.drup.2024.101135","url":null,"abstract":"","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101135"},"PeriodicalIF":15.8,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional relay between Mph(A) enzyme and Mrx efflux pump mediates azithromycin resistance, a novel mechanism of bacterial antimicrobial resistance Mph(A) 酶和 Mrx 外排泵之间的功能中继介导了阿奇霉素耐药性,这是细菌耐药性的一种新机制
IF 15.8 1区 医学
Drug Resistance Updates Pub Date : 2024-08-08 DOI: 10.1016/j.drup.2024.101127
Xuemei Yang , Haoshuai Zhang , Yang Tang , Heng Heng , Yan-Chu Cheung , Xuejiao Song , Hang-Kin Kong , Edward Wai-Chi Chan , Sheng Chen
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