Drug Resistance Updates最新文献

{"title":"Silent circulation of plasmid-borne tet(X6) and blaOXA-58 genes in a community-acquired Acinetobacter baumannii strain","authors":"Huiqiong Jia ,&nbsp;Qingchao Tong ,&nbsp;Le Wang ,&nbsp;Yuye Wu ,&nbsp;Xinyang Li ,&nbsp;Shuangshuang Li ,&nbsp;Yingying Kong ,&nbsp;Yingying Zhang ,&nbsp;João Pedro Rueda Furlan ,&nbsp;Nwai Oo Khine ,&nbsp;Patrick Butaye ,&nbsp;Jun Zhang ,&nbsp;Qing Yang ,&nbsp;Zhi Ruan","doi":"10.1016/j.drup.2024.101194","DOIUrl":"10.1016/j.drup.2024.101194","url":null,"abstract":"<div><div>To characterize the genomic features of a community-acquired <em>Acinetobacter baumannii</em> strain, co-carrying <em>tet</em>(X6) and <em>bla</em>_OXA-58 genes, but was susceptible to tigecycline and carbapenems. The <em>tet</em>(X6) and <em>bla</em>_OXA-58 genes were found on a 149,518 bp non-conjugative plasmid. The <em>bla</em>_OXA-58 gene was silent, due to the presence of an intact IS<em>Aba3</em>-like element upstream, which rendered the strain susceptible to carbapenems.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"79 ","pages":"Article 101194"},"PeriodicalIF":15.8,"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 ,&nbsp;Xiao-xiao Ge ,&nbsp;Xiao-fan Duan ,&nbsp;Jie-qing Li ,&nbsp;Kun Wang ,&nbsp;Qiao-Hong Chen ,&nbsp;Zhi-min Huang ,&nbsp;Wei-yan Zhang ,&nbsp;Yong Wu ,&nbsp;Qun Li","doi":"10.1016/j.drup.2024.101196","DOIUrl":"10.1016/j.drup.2024.101196","url":null,"abstract":"<div><div>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 <em>TRAIL</em> 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.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"79 ","pages":"Article 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 ,&nbsp;Bowen Li ,&nbsp;Wanying Xu,&nbsp;Yuanmengxue Wang,&nbsp;Guoyu Li,&nbsp;Chongpeng Bi,&nbsp;Anshan Shan,&nbsp;Changxuan Shao","doi":"10.1016/j.drup.2024.101183","DOIUrl":"10.1016/j.drup.2024.101183","url":null,"abstract":"<div><h3>Aims</h3><div>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.</div></div><div><h3>Methods</h3><div>In this work, we harvested AMPs with stable antimicrobial activity under the physiological barriers through the combination of idealized amphiphiles and trypsin inhibitors.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"79 ","pages":"Article 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":"Why and how citrate may sensitize malignant tumors to immunotherapy","authors":"Philippe Icard ,&nbsp;Mathilde Prieto ,&nbsp;Antoine Coquerel ,&nbsp;Ludovic Fournel ,&nbsp;Joseph Gligorov ,&nbsp;Johanna Noel ,&nbsp;Adrien Mouren ,&nbsp;Anthony Dohan ,&nbsp;Marco Alifano ,&nbsp;Luca Simula","doi":"10.1016/j.drup.2024.101177","DOIUrl":"10.1016/j.drup.2024.101177","url":null,"abstract":"<div><div>Immunotherapy, either alone or in combination with chemotherapy, has demonstrated limited efficacy in a variety of solid cancers. Several factors contribute to explaining primary or secondary resistance. Among them, cancer cells, whose metabolism frequently relies on aerobic glycolysis, promote exhaustion of cytotoxic immune cells by diverting the glucose in the tumor microenvironment (TME) to their own profit, while secreting lactic acid that sustains the oxidative metabolism of immunosuppressive cells. Here, we propose to combine current treatment based on the use of immune checkpoint inhibitors (ICIs) with high doses of sodium citrate (SCT) because citrate inhibits cancer cell metabolism (by targeting both glycolysis and oxidative metabolism) and may active anti-tumor immune response. Indeed, as showed in preclinical studies, SCT reduces cancer cell growth, promoting cell death and chemotherapy effectiveness. Furthermore, since the plasma membrane citrate carrier pmCIC is mainly expressed in cancer cells and low or not expressed in immune and non-transformed cells, we argue that the inhibition of cancer cell metabolism by SCT may increase glucose availability in the TME, thus promoting functionality of anti-tumor immune cells. Concomitantly, the decrease in the amount of lactic acid in the TME may reduce the functionality of immunosuppressive cells. Preclinical studies have shown that SCT can enhance the anti-tumor immune response through an enhancement of T cell infiltration and activation, and a repolarization of macrophages towards a TAM1-like phenotype. Therefore, this simple and cheap strategy may have a major impact to increase the efficacy of current immunotherapies in human solid tumors and we encourage testing it in clinical trials.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101177"},"PeriodicalIF":15.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721172","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}

{"title":"Blockade of purine metabolism reverses macrophage immunosuppression and enhances anti-tumor immunity in non-small cell lung cancer","authors":"Li Yang ,&nbsp;Aitian Li ,&nbsp;Weina Yu ,&nbsp;Huishang Wang ,&nbsp;Lei Zhang ,&nbsp;Dan Wang ,&nbsp;Ying Wang ,&nbsp;Ru Zhang ,&nbsp;Qingyang Lei ,&nbsp;Zhangnan Liu ,&nbsp;Shanshan Zhen ,&nbsp;Haiming Qin ,&nbsp;Yaqing Liu ,&nbsp;Yang Yang ,&nbsp;Xian-Lu Song ,&nbsp;Yi Zhang","doi":"10.1016/j.drup.2024.101175","DOIUrl":"10.1016/j.drup.2024.101175","url":null,"abstract":"<div><h3>Aims</h3><div>Immune checkpoint blockade therapy is not effective in most patients with non-small cell lung cancer (NSCLC) due to the immunosuppressive tumor microenvironment. Macrophages are key components of tumor-infiltrating immune cells and play a critical role in immunosuppression, which can be mediated by cell-intrinsic metabolism. This study aimed to evaluate whether macrophages regulate NSCLC progression through metabolic crosstalk with cancer cells and affect immunotherapy efficacy.</div></div><div><h3>Methods</h3><div>The macrophage landscape of NSCLC tissues were analyzed by single-cell sequencing and verified through flow cytometry and immunofluorescence. Multiplex assay, single-cell sequencing data, ELISA, immunofluorescence, and RNA-seq et al. were used to investigate and verify the mechanism of macrophage-mediated metabolic regulation on immunosuppression. The tumor-bearing model was established in C57BL/6 J mice to explore in vivo efficacy.</div></div><div><h3>Results</h3><div>We found that tumor tissue-derived macrophages exhibited an anti-inflammatory phenotype and had a prognostic value for NSCLC. NSCLC cell-secreted CXCL8 recruited macrophages from peritumor tissues to tumor sites and promoted programmed death-ligand 1 (PD-L1) expression by activating purine metabolism with increasing xanthine dehydrogenase and uric acid production. Moreover, purine metabolism-mediated macrophage immunosuppression was dependent on NLRP3/caspase-1/IL-1β signaling. Blockade of purine metabolism signaling enhanced anti-tumor immunity and the efficacy of anti-PD-L1 therapy.</div></div><div><h3>Conclusions</h3><div>Collectively, our findings reveal a key role of purine metabolism in macrophage immunosuppression and suggest that blockade of purine metabolism combined with immune checkpoint blockade could provide synergistic effects in NSCLC treatment.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101175"},"PeriodicalIF":15.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721164","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":"Post-translational modifications in drug resistance","authors":"Chenggui Miao ,&nbsp;Yurong Huang ,&nbsp;Cheng Zhang ,&nbsp;Xiao Wang ,&nbsp;Bing Wang ,&nbsp;Xinyue Zhou ,&nbsp;Yingqiu Song ,&nbsp;Peng Wu ,&nbsp;Zhe-Sheng Chen ,&nbsp;Yibin Feng","doi":"10.1016/j.drup.2024.101173","DOIUrl":"10.1016/j.drup.2024.101173","url":null,"abstract":"<div><div>Resistance to antitumor drugs, antimicrobial drugs, and antiviral drugs severely limits treatment effectiveness and cure rate of diseases. Protein post-translational modifications (PTMs) represented by glycosylation, ubiquitination, SUMOylation, acetylation, phosphorylation, palmitoylation, and lactylation are closely related to drug resistance. PTMs are typically achieved by adding sugar chains (glycosylation), small proteins (ubiquitination), lipids (palmitoylation), or functional groups (lactylation) to amino acid residues. These covalent additions are usually the results of signaling cascades and could be reversible, with the triggering mechanisms depending on the type of modifications. PTMs are involved in antitumor drug resistance, not only as inducers of drug resistance but also as targets for reversing drug resistance. Bacteria exhibit multiple PTMs-mediated antimicrobial drug resistance. PTMs allow viral proteins and host cell proteins to form complex interaction networks, inducing complex antiviral drug resistance. This review summarizes the important roles of PTMs in drug resistance, providing new ideas for exploring drug resistance mechanisms, developing new drug targets, and guiding treatment plans.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101173"},"PeriodicalIF":15.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721173","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}

{"title":"AI-driven visualization tool for analyzing data and predicting drug-resistant outbreaks","authors":"Yoshiyasu Takefuji","doi":"10.1016/j.drup.2024.101174","DOIUrl":"10.1016/j.drup.2024.101174","url":null,"abstract":"<div><div>A tool was developed to identify potential disease outbreaks using pathogen and serotype data. By analyzing isolate numbers and comparing them to a two-year average, the tool highlights anomalies suggestive of outbreaks. When applied to Salmonella data, it revealed potential outbreaks related to specific serotypes.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101174"},"PeriodicalIF":15.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693878","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":"Autophagy in cancer development, immune evasion, and drug resistance","authors":"Xuegang Niu ,&nbsp;Qi You ,&nbsp;Kaijian Hou ,&nbsp;Yu Tian ,&nbsp;Penghui Wei ,&nbsp;Yang Zhu ,&nbsp;Bin Gao ,&nbsp;Milad Ashrafizadeh ,&nbsp;Amir Reza Aref ,&nbsp;Alireza Kalbasi ,&nbsp;Israel Cañadas ,&nbsp;Gautam Sethi ,&nbsp;Vinay Tergaonkar ,&nbsp;Lingzhi Wang ,&nbsp;Yuanxiang Lin ,&nbsp;Dezhi Kang ,&nbsp;Daniel J. Klionsky","doi":"10.1016/j.drup.2024.101170","DOIUrl":"10.1016/j.drup.2024.101170","url":null,"abstract":"<div><div>Macroautophagy/autophagy is a highly conserved evolutionary mechanism involving lysosomes for the degradation of cytoplasmic components including organelles. The constitutive, basal level of autophagy is fundamental for preserving cellular homeostasis; however, alterations in autophagy can cause disease pathogenesis, including cancer. The role of autophagy in cancer is particularly complicated, since this process acts both as a tumor suppressor in precancerous stages but facilitates tumor progression during carcinogenesis and later stages of cancer progression. This shift between anti-tumor and pro-tumor roles may be influenced by genetic and environmental factors modulating key pathways such as those involving autophagy-related proteins, the PI3K-AKT-MTOR axis, and AMPK, which often show dysregulation in tumors. Autophagy regulates various cellular functions, including metabolism of glucose, glutamine, and lipids, cell proliferation, metastasis, and several types of cell death (apoptosis, ferroptosis, necroptosis and immunogenic cell death). These multifaceted roles demonstrate the potential of autophagy to affect DNA damage repair, cell death pathways, proliferation and survival, which are critical in determining cancer cells’ response to chemotherapy. Therefore, targeting autophagy pathways presents a promising strategy to combat chemoresistance, as one of the major reasons for the failure in cancer patient treatment. Furthermore, autophagy modulates immune evasion and the function of immune cells such as T cells and dendritic cells, influencing the tumor microenvironment and cancer’s biological behavior. However, the therapeutic targeting of autophagy is complex due to its dual role in promoting survival and inducing cell death in cancer cells, highlighting the need for strategies that consider both the beneficial and detrimental effects of autophagy modulation in cancer therapy. Hence, both inducers and inhibitors of autophagy have been introduced for the treatment of cancer. This review emphasizes the intricate interplay between autophagy, tumor biology, and immune responses, offering insights into potential therapeutic approaches that deploy autophagy in the cancer suppression.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101170"},"PeriodicalIF":15.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721174","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":"Modeling the epidemiologic impact of age-targeted vaccination for drug-resistant tuberculosis","authors":"Pei-Yao Zhai ,&nbsp;Zhi-Xian Chen ,&nbsp;Ting Jiang ,&nbsp;Jian Feng ,&nbsp;Bin Zhang ,&nbsp;Xiao Zang ,&nbsp;Yan-Lin Zhao ,&nbsp;Gang Qin","doi":"10.1016/j.drup.2024.101172","DOIUrl":"10.1016/j.drup.2024.101172","url":null,"abstract":"<div><div>This study used a calibrated mathematical model to evaluate age-specific tuberculosis (TB) vaccination strategies, for drug-resistant (DR)-TB management in China. Prioritizing elderly vaccination significantly reduced multidrug-resistant or rifampicin-resistant TB incidence and mortality, while avoiding the need for second-line treatment, offering a promising approach to mitigate DR-TB burden by 2050.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101172"},"PeriodicalIF":15.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632053","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}