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Drug Metabolism and Disposition: the... Aug 2023Over the past two decades, technological advances in membrane protein structural biology have provided insight into the molecular mechanisms that transporters use to... (Review)
Review
Over the past two decades, technological advances in membrane protein structural biology have provided insight into the molecular mechanisms that transporters use to move diverse substrates across the membrane. However, the plasticity of these proteins' ligand binding pockets, which allows them to bind a range of substrates, also poses a challenge for drug development. Here we highlight the structure, function, and transport mechanism of ATP-binding cassette/solute carrier transporters that are related to several diseases and multidrug resistance: ABCB1, ABCC1, ABCG2, SLC19A1, and SLC29A1. SIGNIFICANCE STATEMENT: ATP-binding cassette transporters and solute carriers play vital roles in clinical chemotherapeutic outcomes. This paper describes the current understanding of the structure of five pharmacologically relevant transporters and how they interact with their ligands.
Topics: Membrane Transport Proteins; Cryoelectron Microscopy; Multidrug Resistance-Associated Proteins; ATP-Binding Cassette Transporters; Drug Resistance, Multiple; Drug Resistance, Neoplasm
PubMed: 37438132
DOI: 10.1124/dmd.122.001004 -
The Veterinary Record Nov 2023
Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial
PubMed: 37975474
DOI: 10.1002/vetr.3671 -
Infectious Disease Clinics of North... Sep 2023The overall burden of the main clinically relevant bacterial multidrug-resistant organisms (MDROs) (eg, methicillin-resistant Staphylococcus aureus, vancomycin-resistant... (Review)
Review
The overall burden of the main clinically relevant bacterial multidrug-resistant organisms (MDROs) (eg, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum β-lactamase producing or extended-spectrum cephalosporin-resistant Enterobacterales, carbapenem-resistant or carbapenemase-producing Enterobacterales, MDR Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii) in solid organ transplant (SOT) populations is summarized showing prevalence/incidence, risk factors, and impact on graft/patient outcome according to the type of SOT. The role of such bacteria in donor-derived infections is also reviewed. As for the management, the main prevention strategies and treatment options are discussed. Finally, nonantibiotic-based strategies are considered as future directions for the management of MDRO in SOT setting.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Methicillin-Resistant Staphylococcus aureus; Organ Transplantation; Transplant Recipients; Vancomycin-Resistant Enterococci
PubMed: 37244806
DOI: 10.1016/j.idc.2023.04.001 -
Current Opinion in Microbiology Oct 2023Bacterial pathogens are constantly evolving new resistance mechanisms against antibiotics; hence, strategies to potentiate existing antibiotics or combat mechanisms of... (Review)
Review
Bacterial pathogens are constantly evolving new resistance mechanisms against antibiotics; hence, strategies to potentiate existing antibiotics or combat mechanisms of resistance using adjuvants are always in demand. Recently, inhibitors have been identified that counteract enzymatic modification of the drugs isoniazid and rifampin, which have implications in the study of multi-drug-resistant mycobacteria. A wealth of structural studies on efflux pumps from diverse bacteria has also fueled the design of new small-molecule and peptide-based agents to prevent the active transport of antibiotics. We envision that these findings will inspire microbiologists to apply existing adjuvants to clinically relevant resistant strains, or to use described platforms to discover novel antibiotic adjuvant scaffolds.
Topics: Bacteria; Anti-Bacterial Agents; Drug Resistance, Microbial; Biological Transport; Drug Resistance, Multiple, Bacterial
PubMed: 37329679
DOI: 10.1016/j.mib.2023.102334 -
Seminars in Cell & Developmental Biology Mar 2024The emergence of therapeutic resistance remains a formidable barrier to durable responses by cancer patients and is a major cause of cancer-related deaths. It is... (Review)
Review
The emergence of therapeutic resistance remains a formidable barrier to durable responses by cancer patients and is a major cause of cancer-related deaths. It is increasingly recognized that non-genetic mechanisms of acquired resistance are important in many cancers. These mechanisms of resistance rely on inherent cellular plasticity where cancer cells can switch between multiple phenotypic states without genetic alterations, providing a dynamic, reversible resistance landscape. Such mechanisms underlie the generation of drug-tolerant persister (DTP) cells, a subpopulation of tumour cells that contributes to heterogeneity within tumours and that supports therapeutic resistance. In this review, we provide an overview of the major features of DTP cells, focusing on phenotypic and metabolic plasticity as two key drivers of tolerance and persistence. We discuss the link between DTP cell plasticity and the potential vulnerability of these cells to ferroptosis. We also discuss the relationship between DTP cells and cells that survive the induction of apoptosis, a process termed anastasis, and discuss the properties of such cells in the context of increased metastatic potential and sensitivity to cell death mechanisms such as ferroptosis.
Topics: Humans; Drug Resistance, Neoplasm; Cell Plasticity; Neoplasms; Apoptosis; Cell Death
PubMed: 37977107
DOI: 10.1016/j.semcdb.2023.11.003 -
Lancet (London, England) Nov 2023
Topics: Humans; Mpox (monkeypox); Drug Resistance, Viral
PubMed: 37951686
DOI: 10.1016/S0140-6736(23)01673-2 -
Blood Sep 2023
Topics: Humans; Drug Resistance, Neoplasm; Mutation; Ubiquitins; Receptor, Notch2
PubMed: 37707876
DOI: 10.1182/blood.2023021142 -
Frontiers in Cellular and Infection... 2023
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gene Transfer, Horizontal; Bacteria
PubMed: 37483384
DOI: 10.3389/fcimb.2023.1240680 -
Expert Opinion on Drug Discovery Feb 2024Malaria remains a devastating infectious disease with hundreds of thousands of casualties each year. Antimalarial drug resistance has been a threat to malaria control... (Review)
Review
INTRODUCTION
Malaria remains a devastating infectious disease with hundreds of thousands of casualties each year. Antimalarial drug resistance has been a threat to malaria control and elimination for many decades and is still of concern today. Despite the continued effectiveness of current first-line treatments, namely artemisinin-based combination therapies, the emergence of drug-resistant parasites in Southeast Asia and even more alarmingly the occurrence of resistance mutations in Africa is of great concern and requires immediate attention.
AREAS COVERED
A comprehensive overview of the mechanisms underlying the acquisition of drug resistance in is given. Understanding these processes provides valuable insights that can be harnessed for the development and selection of novel antimalarials with reduced resistance potential. Additionally, strategies to mitigate resistance to antimalarial compounds on the short term by using approved drugs are discussed.
EXPERT OPINION
While employing strategies that utilize already approved drugs may offer a prompt and cost-effective approach to counter antimalarial drug resistance, it is crucial to recognize that only continuous efforts into the development of novel antimalarial drugs can ensure the successful treatment of malaria in the future. Incorporating resistance propensity assessment during this developmental process will increase the likelihood of effective and enduring malaria treatments.
Topics: Humans; Antimalarials; Malaria; Plasmodium falciparum; Drug Resistance; Drug Discovery
PubMed: 38108082
DOI: 10.1080/17460441.2023.2284820 -
Revue Medicale Suisse May 2024
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Resistance, Microbial
PubMed: 38717003
DOI: 10.53738/REVMED.2024.20.873.946