Drug Resistance Updates最新文献

{"title":"Reshaping the battlefield: A decade of clonal wars among Staphylococcus aureus in China.","authors":"Wangxiao Zhou, Ye Jin, Pan Chen, Qi Ge, Xu Dong, Yunbo Chen, Minghua Jiang, Yonghong Xiao","doi":"10.1016/j.drup.2024.101178","DOIUrl":"10.1016/j.drup.2024.101178","url":null,"abstract":"<p><strong>Background: </strong>Long-term comprehensive studies on the genomic epidemiology of both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) isolates are limited in China. Here, we aimed to assess the genomic epidemiological characteristics and population dynamics of S. aureus in China.</p><p><strong>Methods: </strong>We performed whole-genome sequencing and resistance phenotyping on 3848 S. aureus isolates from bloodstream infections across 72 hospitals in 22 provinces, from 2011 to 2020 in China. We explored the dynamic trends in the resistance/virulence genes and mobile genetic element profiles across lineages, and conducted time-scaled phylogenetic investigation for prevalent lineages.</p><p><strong>Findings: </strong>The results revealed 315 different sequence types (STs) among all strains, 205 of which were novel. Significant shifts in MRSA population structure were observed, with ST59 replacing ST239 as the dominant lineage, exhibiting widespread inter-hospital transmission and increasing lineage diversity. In contrast, the composition of predominant MSSA lineages, ST188 (11.21 %), ST7 (9.79 %), ST22 (9.10 %), ST5 (8.56 %) and ST398 (7.91 %), remained relatively stable over time, with the diversity among MSSA strains consistently preserved at the population level. Phylogenetic reconstruction showed that ST59, ST398, ST22 and ST188 MSSA could evolve into corresponding MRSA lineages through the acquisition of staphylococcal cassette chromosome mec (SCCmec) elements. Moreover, the distribution patterns of resistance and virulence genes closely correlated with different lineages, where the proportion of PVL⁺ isolates in MRSA is rising. Concurrently, changes in the MRSA population structure led to an overall decrease in the number of resistance and virulence genes, significantly increased antimicrobial sensitivity.</p><p><strong>Interpretation: </strong>The shifting genomic landscape of S. aureus in China underscores the need for tailored antimicrobial stewardship and enhances understanding of its epidemiological trends over the past decade.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"101178"},"PeriodicalIF":15.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774229","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}

{"title":"Fasting-mimicking diet potentiates anti-tumor effects of CDK4/6 inhibitors against breast cancer by suppressing NRAS- and IGF1-mediated mTORC1 signaling.","authors":"Sebastian Brandhorst, Valter D Longo","doi":"10.1016/j.drup.2024.101182","DOIUrl":"10.1016/j.drup.2024.101182","url":null,"abstract":"<p><p>Fasting-mimicking diet (FMD) cycles, defined as 3-5 day periods of a calorie-restricted, low-protein, low-carbohydrate, and high-fat diet, have emerged as a dietary approach to delay cancer initiation and progression in both autograft and xenograft mouse models and as a safe and feasible approach to decrease risk factors for cancer and other age-related pathologies in humans. A substantial number of pre-clinical studies focused on various tumor types have shown that fasting/FMDs can potentiate the efficacy of various standard-of-care cancer therapies but also modulate the immune system to promote a T cell-dependent attack of tumor cells. Importantly, combining drug treatment with fasting/FMDs can overcome acquired drug resistance which frequently emerges and reduces long-term treatment benefits. However, the mechanisms by which the FMD reverts resistance to CDK4/6i remain poorly understood. Here, Li and colleagues provide evidence that FMD cycles act as a wild card to reduce the activity of a signaling network that includes IGF-1, RAS, AKT, and mTOR-S6K to delay cancer progression and reverse the acquisition of drug resistance. These findings expand the mechanistic understanding of the FMD-mediated increase in drug efficacy and provide further evidence to support trials combining hormone therapy, CDK4/6 inhibitors, and FMD in breast cancer treatment. These new results on FMD cycles add an optimistic outlook to extend the efficacy of standard-of-care drugs that eventually become ineffective because of acquired resistance.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":" ","pages":"101182"},"PeriodicalIF":15.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814603","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}

{"title":"Molecular subtype changes after acquiring resistance to tarlatamab in small cell lung cancer.","authors":"Hyung-Min Ahn, Seog-Yun Park, Yura Choi, Jaemin Kim, Youngjoo Lee","doi":"10.1016/j.drup.2024.101198","DOIUrl":"https://doi.org/10.1016/j.drup.2024.101198","url":null,"abstract":"<p><p>Tarlatamab, a novel bispecific T-cell engager, has demonstrated unprecedented efficacy in patients with small cell lung cancer. However, there is no known mechanism of resistance to tarlatamab. This study suggests that a transcriptional expression shift might be associated with acquired resistance to tarlatamab.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"79 ","pages":"101198"},"PeriodicalIF":15.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916197","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}

{"title":"N6-methyladenosine modification of 3'tRF-AlaAGC impairs PD-1 blockade efficacy by promoting lactic acid accumulation in the tumor microenvironment of gastric carcinoma.","authors":"Weiguo Xu, Bin Zhou, Ping Wang, Yuyan Ma, Yu Jiang, Dongping Mo, Jun Wu, Jingjing Ma, Xiao Wang, Yinxing Miao, Yong Nian, Junyu Zheng, Jie Li, Feng Yan, Gang Li","doi":"10.1016/j.drup.2024.101197","DOIUrl":"https://doi.org/10.1016/j.drup.2024.101197","url":null,"abstract":"<p><p>The balance between CD8⁺ T cells and regulatory T (Treg) cells in the tumor microenvironment (TME) plays a crucial role in the immune checkpoint inhibition (ICI) therapy in gastric carcinoma (GC). However, related factors leading to the disturbance of TME and resistance to ICI therapy remain unknown. In this study, we applied N6-methyladenosine (m6A) small RNA Epitranscriptomic Microarray and screened out 3'tRF-AlaAGC based on its highest differential expression level and lowest inter-group variance. N6-methyladenosine modification significantly enhanced the stability of 3'tRF-AlaAGC, which strengthened glycolysis and lactic acid (LA) production in GC cells by binding to PTBP1 (Polypyrimidine Tract Binding Protein 1). In the peritoneal GC implantation model established in huPBMC-NCG mice, 3'tRF-AlaAGC significantly increased the proportion of PD1⁺ Treg cells. Furthermore, in high-LA environments driven by glucose consumption of GC cells, Treg cells actively uptake LA through MCT1, facilitating NFAT1 translocation into the nucleus and enhancing PD1 expression, whereas PD1 expression by effector T cell is diminished. Meanwhile, T cell suppression assays were performed under low-LA or high-LA conditions, and the proliferation of CD8⁺ T cells was dampened by adding Sintilimab in a high-LA but not in a low-LA environment, suggesting the preferential activation of PD1⁺ Treg cell. These findings deciphered the complexities of the immune microenvironment in GC, providing prospects for identifying robust biomarkers that could improve the evaluation of therapeutic effectiveness and prognosis in immune therapy for GC.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"79 ","pages":"101197"},"PeriodicalIF":15.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928724","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}

{"title":"Research progress on gene mutations and drug resistance in leukemia.","authors":"Xiangyu Ma, Jiamin Xu, Yanan Wang, Joshua S Fleishman, Hao Bing, Boran Yu, Yanming Li, Letao Bo, Shaolong Zhang, Zhe-Sheng Chen, Libo Zhao","doi":"10.1016/j.drup.2024.101195","DOIUrl":"https://doi.org/10.1016/j.drup.2024.101195","url":null,"abstract":"<p><p>Leukemia is a type of blood cancer characterized by the uncontrolled growth of abnormal cells in the bone marrow, which replace normal blood cells and disrupt normal blood cell function. Timely and personalized interventions are crucial for disease management and improving survival rates. However, many patients experience relapse following conventional chemotherapy, and increasing treatment intensity often fails to improve outcomes due to mutated gene-induced drug resistance in leukemia cells. This article analyzes the association of gene mutations and drug resistance in leukemia. It explores genetic abnormalities in leukemia, highlighting recently identified mutations affecting signaling pathways, cell apoptosis, epigenetic regulation, histone modification, and splicing mechanisms. Additionally, the article discusses therapeutic strategies such as molecular targeting of gene mutations, alternative pathway targeting, and immunotherapy in leukemia. These approaches aim to combat specific drug-resistant mutations, providing potential avenues to mitigate leukemia relapse. Future research with these strategies holds promise for advancing leukemia treatment and addressing the challenges of drug-resistant mutations to improve patient outcomes.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"79 ","pages":"101195"},"PeriodicalIF":15.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911107","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}

{"title":"Silent circulation of plasmid-borne tet(X6) and blaOXA-58 genes in a community-acquired Acinetobacter baumannii strain","authors":"Huiqiong Jia, Qingchao Tong, Le Wang, Yuye Wu, Xinyang Li, Shuangshuang Li, Yingying Kong, Yingying Zhang, João Pedro Rueda Furlan, Nwai Oo Khine, Patrick Butaye, Jun Zhang, Qing Yang, Zhi Ruan","doi":"10.1016/j.drup.2024.101194","DOIUrl":"https://doi.org/10.1016/j.drup.2024.101194","url":null,"abstract":"To characterize the genomic features of a community-acquired <ce:italic>Acinetobacter baumannii</ce:italic> strain, co-carrying <ce:italic>tet</ce:italic>(X6) and <ce:italic>bla</ce:italic><ce:inf loc=\"post\">OXA-58</ce:inf> genes, but was susceptible to tigecycline and carbapenems. The <ce:italic>tet</ce:italic>(X6) and <ce:italic>bla</ce:italic><ce:inf loc=\"post\">OXA-58</ce:inf> genes were found on a 149,518 bp non-conjugative plasmid. The <ce:italic>bla</ce:italic><ce:inf loc=\"post\">OXA-58</ce:inf> gene was silent, due to the presence of an intact IS<ce:italic>Aba3</ce:italic>-like element upstream, which rendered the strain susceptible to carbapenems.","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"5 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142889253","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}

{"title":"Wip1 phosphatase activator QGC-8-52 specifically sensitizes p53-negative cancer cells to chemotherapy while protecting normal cells.","authors":"Ke Wu, Xiao-Xiao Ge, Xiao-Fan Duan, Jie-Qing Li, Kun Wang, Qiao-Hong Chen, Zhi-Min Huang, Wei-Yan Zhang, Yong Wu, Qun Li","doi":"10.1016/j.drup.2024.101196","DOIUrl":"10.1016/j.drup.2024.101196","url":null,"abstract":"<p><p>PP2C serine-threonine phosphatase Wip1 plays an important role in normal tissue homeostasis, stress signaling and pathogenesis of various human diseases. It is an attractive drug target for cancer treatment and inhibition of its expression or activity constitute a novel therapeutic intervention strategy to prevent the development of various cancers. However, previous strategies for Wip1 suppression may be ineffective in cancers lacking p53. Here, we have characterized the activity of a novel Wip1 phosphatase activator, QGC-8-52, in preclinical models of breast malignancies. QGC-8-52 significantly sensitizes the cancer cell lines with p53 deletion to chemotherapeutic agents. This effect was mediated by the Wip1-FOXO3a interaction and subsequent dephosphorylation of Thr487 that resulted, in response to anticancer treatment, in enhancing the transcription activity of FOXO3a on the proapoptotic TRAIL gene. The sensitizing effect of Wip1 activation on chemotherapeutic drugs only targeted cancer cells lacking p53. The activation of Wip1 in normal cells provided protection from anticancer drug-induced apoptosis by reducing the strength of upstream signaling to p53. Therefore, during the treatment of anticancer drugs, the activated Wip1 phosphatase boosts the apoptosis of p53-negative tumors and protects normal tissues. Our findings may represent an effective and safe therapeutic strategy for cancers with p53 deletion.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"79 ","pages":"101196"},"PeriodicalIF":15.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958365","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}

{"title":"WITHDRAWN: Low miR-224-5p in exosomes confers colorectal cancer 5-FU resistance by upregulating S100A4","authors":"Yan-yan Yan, Zhuo-fen Deng, Xing-tao Wu, Yu Lu, Zhuang-yan Zhu, Qing Wen, Wei Zhang, Hai-yan Zhang, Xin-zhu Chen, Yu-song Wu, Xue-bing He, Zi-ang Ma, Jin-shuo Li, Hong Bi, Jian-ye Zhang","doi":"10.1016/j.drup.2024.101193","DOIUrl":"https://doi.org/10.1016/j.drup.2024.101193","url":null,"abstract":"","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"4 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142889235","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}

{"title":"Association of idealized amphiphiles and protease inhibitors: Conferring antimicrobial peptides with stable antibacterial activity under physiological conditions to combat multidrug-resistant bacteria.","authors":"Yongjie Zhu, Bowen Li, Wanying Xu, Yuanmengxue Wang, Guoyu Li, Chongpeng Bi, Changxuan Shao, Anshan Shan","doi":"10.1016/j.drup.2024.101183","DOIUrl":"https://doi.org/10.1016/j.drup.2024.101183","url":null,"abstract":"<p><strong>Aims: </strong>The unstable antimicrobial activity of antimicrobial peptides (AMPs) under physiological conditions (especially the degradation instigated proteases) seems to be a persistent impediment for their successful implementation in clinical trials. Consequently, our objective was to devise AMP engineering frameworks that could sustain robust antibacterial efficacy within physiological environments.</p><p><strong>Methods: </strong>In this work, we harvested AMPs with stable antimicrobial activity under the physiological barriers through the combination of idealized amphiphiles and trypsin inhibitors.</p><p><strong>Results: </strong>We screened and identified the lead peptides IK3-A and IK3-S, which showed potent activity against Gram-negative bacteria, including multidrug-resistant (MDR) bacteria, and exhibited promising biocompatibility with mammalian cells. Remarkably, IK3-A and IK3-S maintained sustained antibacterial potency under physiological salts, serum, and protease conditions. Furthermore, both IK3-A and IK3-S kill Gram-negative bacteria by attacking the bacterial cell membrane and inducing oxidative damage (at high concentrations). Crucially, IK3-A and IK3-S have optimal safety and efficacy in mice.</p><p><strong>Conclusions: </strong>This is the first work to compare the effects of different trypsin inhibitors on the resistance of AMPs to protease hydrolysis on the same sequence platform. In conclusion, these findings provide guidance for the molecular design of AMPs with stable antibacterial activity under physiological conditions and facilitates the process of clinical translation of AMPs as antimicrobial biomaterials against MDR bacteria. Moreover, this may stimulate a more general interest in protease inhibitors as molecular scaffolds in the creation of highly stable peptide-based biomaterials.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"79 ","pages":"101183"},"PeriodicalIF":15.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820132","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}

{"title":"CEA-induced PI3K/AKT pathway activation through the binding of CEA to KRT1 contributes to oxaliplatin resistance in gastric cancer","authors":"Yifan Chen, Yulong Mi, Song Tan, Yizhen Chen, Shaolin Liu, Shengtao Lin, Changshun Yang, Weifeng Hong, Weihua Li","doi":"10.1016/j.drup.2024.101179","DOIUrl":"https://doi.org/10.1016/j.drup.2024.101179","url":null,"abstract":"The serum level of carcinoembryonic antigen (CEA) has prognostic value in patients with gastric cancer (GC) receiving oxaliplatin-based chemotherapy. As the molecular functions of CEA are increasingly uncovered, its role in regulating oxaliplatin resistance in GC attracts attention.","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"219 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790068","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}