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British Journal of Biomedical Science 2023Antimicrobial resistance (AMR) has now emerged as a chronic public health problem globally, with the forecast of 10 million deaths per year globally by 2050. AMR occurs... (Review)
Review
Antimicrobial resistance (AMR) has now emerged as a chronic public health problem globally, with the forecast of 10 million deaths per year globally by 2050. AMR occurs when viruses, bacteria, fungi and parasites do not respond to antimicrobial treatments in humans and animals, thus allowing the survival of the microorganism within the host. The prominent cause contributing to the current crisis remains to be the overuse and misuse of antimicrobials, particularly the inappropriate usage of antibiotics, increasing the global burden of antimicrobial resistance. The global consumption and usage of antibiotics are therefore closely monitored at all times. This review provides a current overview of the implications of strategies used by international governmental organisations, including the UN's 17 Sustainable Development Goals (SDGs), to address the problem of antibiotic resistance, as well as the "," a system incorporating a multidisciplinary effort to achieve the best possible health outcome by acknowledging the clear connections between humans, animals and their shared environment. The importance of public awareness and health literacy of lay audiences still needs to be further emphasised as part of global and local action plans. Antimicrobial resistance continues to be a major global public health dilemma of the 21st century. Already this topic is receiving substantial political input from the G7 countries and continues to be on the agenda of numerous political conferences. The consequences of failure to adequately address AMR are profound, with estimations of a return to the pre-antibiotic era, where everyday infections relating to childbirth, surgery and open fractured limbs could be potentially life-threatening. AMR itself represents a microcosm of factors, including social anthropology, civil unrest/war, diasporas, ethnic displacement, political systems, healthcare, economics, societal behaviour both at a population and individual level, health literacy, geoclimatic events, global travel and pharmaceutical innovation and investment, thus finding a solution that adequately addresses AMR and which helps stem further AMR emergence is complicated. Success will involve individuals, communities and nations all working together to ensure that the world continues to possess a sufficient armamentarium of effective antimicrobials that will sustain human and animal health, both now and in the future.
Topics: Animals; Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Anti-Infective Agents
PubMed: 37448857
DOI: 10.3389/bjbs.2023.11387 -
Nature Aug 2023Even among genetically identical cancer cells, resistance to therapy frequently emerges from a small subset of those cells. Molecular differences in rare individual...
Even among genetically identical cancer cells, resistance to therapy frequently emerges from a small subset of those cells. Molecular differences in rare individual cells in the initial population enable certain cells to become resistant to therapy; however, comparatively little is known about the variability in the resistance outcomes. Here we develop and apply FateMap, a framework that combines DNA barcoding with single-cell RNA sequencing, to reveal the fates of hundreds of thousands of clones exposed to anti-cancer therapies. We show that resistant clones emerging from single-cell-derived cancer cells adopt molecularly, morphologically and functionally distinct resistant types. These resistant types are largely predetermined by molecular differences between cells before drug addition and not by extrinsic factors. Changes in the dose and type of drug can switch the resistant type of an initial cell, resulting in the generation and elimination of certain resistant types. Samples from patients show evidence for the existence of these resistant types in a clinical context. We observed diversity in resistant types across several single-cell-derived cancer cell lines and cell types treated with a variety of drugs. The diversity of resistant types as a result of the variability in intrinsic cell states may be a generic feature of responses to external cues.
Topics: Humans; Clone Cells; DNA Barcoding, Taxonomic; Drug Resistance, Neoplasm; Neoplasms; RNA-Seq; Single-Cell Gene Expression Analysis; Tumor Cells, Cultured; Antineoplastic Agents
PubMed: 37468627
DOI: 10.1038/s41586-023-06342-8 -
Cell Reports Jul 2023The bone marrow microenvironment (BME) drives drug resistance in acute lymphoblastic leukemia (ALL) through leukemic cell interactions with bone marrow (BM) niches, but...
The bone marrow microenvironment (BME) drives drug resistance in acute lymphoblastic leukemia (ALL) through leukemic cell interactions with bone marrow (BM) niches, but the underlying mechanisms remain unclear. Here, we show that the interaction between ALL and mesenchymal stem cells (MSCs) through integrin β1 induces an epithelial-mesenchymal transition (EMT)-like program in MSC-adherent ALL cells, resulting in drug resistance and enhanced survival. Moreover, single-cell RNA sequencing analysis of ALL-MSC co-culture identifies a hybrid cluster of MSC-adherent ALL cells expressing both B-ALL and MSC signature genes, orchestrated by a WNT/β-catenin-mediated EMT-like program. Blockade of interaction between β-catenin and CREB binding protein impairs the survival and drug resistance of MSC-adherent ALL cells in vitro and results in a reduction in leukemic burden in vivo. Targeting of this WNT/β-catenin-mediated EMT-like program is a potential therapeutic approach to overcome cell extrinsically acquired drug resistance in ALL.
Topics: Humans; Epithelial-Mesenchymal Transition; beta Catenin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Coculture Techniques; Drug Resistance; Cell Proliferation; Tumor Microenvironment
PubMed: 37453060
DOI: 10.1016/j.celrep.2023.112804 -
Drug Resistance Updates : Reviews and... Jan 2024Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role of copper and copper triggered cell death in the pathogenesis of cancers have... (Review)
Review
Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role of copper and copper triggered cell death in the pathogenesis of cancers have attracted attentions. Cuproptosis has garnered enormous interest in cancer research communities because of its great potential for cancer therapy. Copper-based treatment exerts an inhibiting role in tumor growth and may open the door for the treatment of chemotherapy-insensitive tumors. In this review, we provide a critical analysis on copper homeostasis and the role of copper dysregulation in the development and progression of cancers. Then the core molecular mechanisms of cuproptosis and its role in cancer is discussed, followed by summarizing the current understanding of copper-based agents (copper chelators, copper ionophores, and copper complexes-based dynamic therapy) for cancer treatment. Additionally, we summarize the emerging data on copper complexes-based agents and copper ionophores to subdue tumor chemotherapy resistance in different types of cancers. We also review the small-molecule compounds and nanoparticles (NPs) that may kill cancer cells by inducing cuproptosis, which will shed new light on the development of anticancer drugs through inducing cuproptosis in the future. Finally, the important concepts and pressing questions of cuproptosis in future research that should be focused on were discussed. This review article suggests that targeting cuproptosis could be a novel antitumor therapy and treatment strategy to overcome cancer drug resistance.
Topics: Humans; Copper; Drug Resistance, Neoplasm; Cell Death; Ionophores; Neoplasms; Apoptosis
PubMed: 37979442
DOI: 10.1016/j.drup.2023.101018 -
International Journal For Parasitology Jul 2023
Topics: Anthelmintics; Vaccines; Drug Resistance
PubMed: 37257805
DOI: 10.1016/j.ijpara.2023.05.004 -
Current Opinion in Microbiology Aug 2023Antimicrobial susceptibility testing is the cornerstone of antibiotic treatments. Yet, active drugs are frequently unsuccessful in vivo and most clinical trials... (Review)
Review
Antimicrobial susceptibility testing is the cornerstone of antibiotic treatments. Yet, active drugs are frequently unsuccessful in vivo and most clinical trials investigating antibiotics fail. So far, bacterial survival strategies, other than drug resistance, have been largely ignored. As such, drug tolerance and persisters, allowing bacterial populations to survive during antibiotic treatments, could fill a gap in antibiotic susceptibility testing. Therefore, it remains critical to establish robust and scalable bacterial viability measures and to define the clinical relevance of bacterial survivors across various bacterial infections. If successful, these tools could improve drug design and development to prevent tolerance formation or target bacterial survivors, to ultimately reduce treatment failures and curb resistance evolution.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Drug Tolerance
PubMed: 37245488
DOI: 10.1016/j.mib.2023.102328 -
International Journal of Molecular... Sep 2023This Special Issue-dedicated to high-quality review papers in molecular microbiology-is highlighting two important developments in the field: (i) the analysis of...
This Special Issue-dedicated to high-quality review papers in molecular microbiology-is highlighting two important developments in the field: (i) the analysis of microbiome data in health and disease and (ii) the search for strategies against bacteria showing antimicrobial resistance [...].
Topics: Microbiota; Review Literature as Topic; Drug Resistance, Bacterial
PubMed: 37762293
DOI: 10.3390/ijms241813990 -
Current Opinion in Microbiology Aug 2023Bacteria are single-celled organisms, but the survival of microbial communities relies on complex dynamics at the molecular, cellular, and ecosystem scales. Antibiotic... (Review)
Review
Bacteria are single-celled organisms, but the survival of microbial communities relies on complex dynamics at the molecular, cellular, and ecosystem scales. Antibiotic resistance, in particular, is not just a property of individual bacteria or even single-strain populations, but depends heavily on the community context. Collective community dynamics can lead to counterintuitive eco-evolutionary effects like survival of less resistant bacterial populations, slowing of resistance evolution, or population collapse, yet these surprising behaviors are often captured by simple mathematical models. In this review, we highlight recent progress - in many cases, advances driven by elegant combinations of quantitative experiments and theoretical models - in understanding how interactions between bacteria and with the environment affect antibiotic resistance, from single-species populations to multispecies communities embedded in an ecosystem.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Models, Theoretical; Microbiota; Bacteria
PubMed: 37054512
DOI: 10.1016/j.mib.2023.102306 -
International Journal of Molecular... Jul 2023One of the leading causes of death worldwide, in both men and women, is cancer. Despite the significant development in therapeutic strategies, the inevitable emergence... (Review)
Review
One of the leading causes of death worldwide, in both men and women, is cancer. Despite the significant development in therapeutic strategies, the inevitable emergence of drug resistance limits the success and impedes the curative outcome. Intrinsic and acquired resistance are common mechanisms responsible for cancer relapse. Several factors crucially regulate tumourigenesis and resistance, including physical barriers, tumour microenvironment (TME), heterogeneity, genetic and epigenetic alterations, the immune system, tumour burden, growth kinetics and undruggable targets. Moreover, transforming growth factor-beta (TGF-β), Notch, epidermal growth factor receptor (EGFR), integrin-extracellular matrix (ECM), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), wingless-related integration site (Wnt/β-catenin), Janus kinase/signal transducers and activators of transcription (JAK/STAT) and RAS/RAF/mitogen-activated protein kinase (MAPK) signalling pathways are some of the key players that have a pivotal role in drug resistance mechanisms. To guide future cancer treatments and improve results, a deeper comprehension of drug resistance pathways is necessary. This review covers both intrinsic and acquired resistance and gives a comprehensive overview of recent research on mechanisms that enable cancer cells to bypass barriers put up by treatments, and, like "satellite navigation", find alternative routes by which to carry on their "journey" to cancer progression.
Topics: Male; Humans; Female; Phosphatidylinositol 3-Kinases; Neoplasm Recurrence, Local; Signal Transduction; Antineoplastic Agents; Drug Resistance; Tumor Microenvironment
PubMed: 37569598
DOI: 10.3390/ijms241512222 -
Frontiers in Cellular and Infection... 2023
Topics: Antimalarials; Insecticide Resistance
PubMed: 37719669
DOI: 10.3389/fcimb.2023.1274741