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Philosophical Transactions of the Royal... Mar 2014Multi-drug resistance (MDR) to chemotherapy is the major challenge in the treatment of cancer. MDR can develop by numerous mechanisms including decreased drug uptake,... (Review)
Review
Multi-drug resistance (MDR) to chemotherapy is the major challenge in the treatment of cancer. MDR can develop by numerous mechanisms including decreased drug uptake, increased drug efflux and the failure to undergo drug-induced apoptosis. Evasion of drug-induced apoptosis through modulation of ion transporters is the main focus of this paper and we demonstrate how pro-apoptotic ion channels are downregulated, while anti-apoptotic ion transporters are upregulated in MDR. We also discuss whether upregulation of ion transport proteins that are important for proliferation contribute to MDR. Finally, we discuss the possibility that the development of MDR involves sequential and localized upregulation of ion channels involved in proliferation and migration and a concomitant global and persistent downregulation of ion channels involved in apoptosis.
Topics: Apoptosis; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Ion Channels; Ion Transport; Models, Biological; Neoplasms
PubMed: 24493757
DOI: 10.1098/rstb.2013.0109 -
Daru : Journal of Faculty of Pharmacy,... Jun 2020Infectious diseases associated with intracellular bacteria such as Staphylococcus aureus, Salmonella typhimurium and Mycobacterium tuberculosis are important public... (Review)
Review
INTRODUCTION
Infectious diseases associated with intracellular bacteria such as Staphylococcus aureus, Salmonella typhimurium and Mycobacterium tuberculosis are important public health concern. Emergence of multi and extensively drug-resistant bacterial strains have made it even more obstinate to offset such infections. Bacteria residing within intracellular compartments provide additional barriers to effective treatment.
METHOD
Information provided in this review has been collected by accessing various electronic databases including Google scholar, Web of science, Scopus, and Nature index. Search was performed using keywords nanoparticles, intracellular targeting, multidrug resistance, Staphylococcus aureus; Salmonella typhimurium; Mycobacterium tuberculosis. Information gathered was categorized into three major sections as 'Intracellular targeting of Staphylococcus aureus, Intracellular targeting of Salmonella typhimurium and Intracellular targeting of Mycobacterium tuberculosis' using variety of nanocarrier systems.
RESULTS
Conventional management for infectious diseases typically comprises of long-term treatment with a combination of antibiotics, which may lead to side effects and decreased patient compliance. A wide range of multi-functionalized nanocarrier systems have been studied for delivery of drugs within cellular compartments where bacteria including Staphylococcus aureus, Salmonella typhimurium and Mycobacterium tuberculosis reside. Such carrier systems along with targeted delivery have been utilized for sustained and controlled delivery of drugs. These strategies have been found useful in overcoming the drawbacks of conventional treatments including multi-drug resistance.
CONCLUSION
Development of multi-functional nanocargoes encapsulating antibiotics that are proficient in targeting and releasing drug into infected reservoirs seems to be a promising strategy to circumvent the challenge of multidrug resistance. Graphical abstract.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Drug Carriers; Drug Resistance, Multiple, Bacterial; Humans; Nanoparticles
PubMed: 32193748
DOI: 10.1007/s40199-020-00337-w -
BMC Research Notes Nov 2017Multidrug resistance (MDR) and extended spectrum beta lactamase (ESBL) producer Gram negative bacteria are considered as a major health problem, globally. ESBL enzyme...
OBJECTIVE
Multidrug resistance (MDR) and extended spectrum beta lactamase (ESBL) producer Gram negative bacteria are considered as a major health problem, globally. ESBL enzyme hydrolyses the beta lactam ring of third generation cephalosporins, which alters the structure of the antibiotic. Due to the modification in structure of the antibiotic, bacteria show resistance to these antibiotics. Resistant bacterial strains are transmitted to humans from animals through consumption of uncooked meat, through contact with uncooked meat and meat surfaces. This study aims to assess bacteriological profile and analyze the situation of antibiotic resistance, multidrug resistance, and ESBL producing Gram negative bacteria in chicken meat.
RESULTS
A total of 38 chicken meat samples were studied in which 103 Gram negative bacteria were isolated. Species of Gram negative bacteria were identified as Citrobacter spp. (44.7%), Salmonella spp. (26.2%), Proteus spp. (18.4%), Escherichia coli (4.8%), Shigella spp. (3.9%), Pseudomonas spp. (1.9%), and Klebsiella spp. (1.0%). The prevalence of MDR isolates was found to be 79.6%. Total ESBL producer was 36.9% and ESBL producer among MDR was 34.9%. This concludes wide range of antibiotic resistance bacteria is prevalent in raw chicken meat.
Topics: Animals; Chickens; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Nepal; beta-Lactam Resistance; beta-Lactamases
PubMed: 29116010
DOI: 10.1186/s13104-017-2917-x -
Journal of Controlled Release :... Oct 2011Inefficiencies in systemic drug delivery and tumor residence as well as micro-environmental selection pressures contribute to the development of multidrug resistance... (Review)
Review
Inefficiencies in systemic drug delivery and tumor residence as well as micro-environmental selection pressures contribute to the development of multidrug resistance (MDR) in cancer. Characteristics of MDR include abnormal vasculature, regions of hypoxia, up-regulation of ABC-transporters, aerobic glycolysis, and an elevated apoptotic threshold. Nano-sized delivery vehicles are ideal for treating MDR cancer as they can improve the therapeutic index of drugs and they can be engineered to achieve multifunctional parameters. The multifunctional ability of nanocarriers makes them more adept at treating heterogeneous tumor mass than traditional chemotherapy. Nanocarriers also have preferential tumor accumulation via the EPR effect; this accumulation can be further enhanced by actively targeting the biological profile of MDR cells. Perhaps the most significant benefit of using nanocarrier drug delivery to treat MDR cancer is that nanocarrier delivery diverts the effects of ABC-transporter mediated drug efflux; which is the primary mechanism of MDR. This review discusses the capabilities, applications, and examples of multifunctional nanocarriers for the treatment of MDR. This review emphasizes multifunctional nanocarriers that enhance drug delivery efficiency, the application of RNAi, modulation of the tumor apoptotic threshold, and physical approaches to overcome MDR.
Topics: Adenosine Triphosphate; Antineoplastic Agents; Apoptosis; Cell Hypoxia; Combined Modality Therapy; Drug Carriers; Drug Delivery Systems; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Glycolysis; Humans; Nanotechnology; Neoplasms; Neoplastic Stem Cells
PubMed: 21497176
DOI: 10.1016/j.jconrel.2011.03.032 -
BMC Infectious Diseases May 2023The World Health Organization has reported that the treatment success rate of multi-drug resistance tuberculosis is approximately 57% globally. Although new drugs such...
BACKGROUND
The World Health Organization has reported that the treatment success rate of multi-drug resistance tuberculosis is approximately 57% globally. Although new drugs such as bedaquiline and linezolid is likely improve the treatment outcome, there are other factors associated with unsuccessful treatment outcome. The factors associated with unsuccessful treatment outcomes have been widely examined, but only a few studies have developed prediction models. We aimed to develop and validate a simple clinical prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance pulmonary tuberculosis (MDR-PTB).
METHODS
This retrospective cohort study was performed between January 2017 and December 2019 at a special hospital in Xi'an, China. A total of 446 patients with MDR-PTB were included. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to select prognostic factors for unsuccessful treatment outcomes. A nomogram was built based on four prognostic factors. Internal validation and leave-one-out cross-validation was used to assess the model.
RESULTS
Of the 446 patients with MDR-PTB, 32.9% (147/446) cases had unsuccessful treatment outcomes, and 67.1% had successful outcomes. After LASSO regression and multivariate logistic analyses, no health education, advanced age, being male, and larger extent lung involvement were identified as prognostic factors. These four prognostic factors were used to build the prediction nomograms. The area under the curve of the model was 0.757 (95%CI 0.711 to 0.804), and the concordance index (C-index) was 0.75. For the bootstrap sampling validation, the corrected C-index was 0.747. In the leave-one-out cross-validation, the C-index was 0.765. The slope of the calibration curve was 0.968, which was approximately 1.0. This indicated that the model was accurate in predicting unsuccessful treatment outcomes.
CONCLUSIONS
We built a predictive model and established a nomogram for unsuccessful treatment outcomes of multi-drug resistance pulmonary tuberculosis based on baseline characteristics. This predictive model showed good performance and could be used as a tool by clinicians to predict who among their patients will have an unsuccessful treatment outcome.
Topics: Humans; Male; Female; Retrospective Studies; Models, Statistical; Prognosis; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Drug Resistance, Multiple
PubMed: 37147607
DOI: 10.1186/s12879-023-08193-0 -
Frontiers in Cellular and Infection... 2022Emerging antibiotic resistance in bacteria endorses the failure of existing drugs with chronic illness, complicated treatment, and ever-increasing expenditures. Bacteria... (Review)
Review
Emerging antibiotic resistance in bacteria endorses the failure of existing drugs with chronic illness, complicated treatment, and ever-increasing expenditures. Bacteria acquire the nature to adapt to starving conditions, abiotic stress, antibiotics, and our immune defense mechanism due to its swift evolution. The intense and inappropriate use of antibiotics has led to the development of multidrug-resistant (MDR) strains of bacteria. Phytochemicals can be used as an alternative for complementing antibiotics due to their variation in metabolic, genetic, and physiological fronts as well as the rapid evolution of resistant microbes and lack of tactile management. Several phytochemicals from diverse groups, including alkaloids, phenols, coumarins, and terpenes, have effectively proved their inhibitory potential against MDR pathogens through their counter-action towards bacterial membrane proteins, efflux pumps, biofilms, and bacterial cell-to-cell communications, which are important factors in promoting the emergence of drug resistance. Plant extracts consist of a complex assortment of phytochemical elements, against which the development of bacterial resistance is quite deliberate. This review emphasizes the antibiotic resistance mechanisms of bacteria, the reversal mechanism of antibiotic resistance by phytochemicals, the bioactive potential of phytochemicals against MDR, and the scientific evidence on molecular, biochemical, and clinical aspects to treat bacterial pathogenesis in humans. Moreover, clinical efficacy, trial, safety, toxicity, and affordability investigations, current status and developments, related demands, and future prospects are also highlighted.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Proteins; Biofilms; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Phytochemicals
PubMed: 35846771
DOI: 10.3389/fcimb.2022.883839 -
Current Opinion in Pharmacology Oct 2013This special issue of Current Opinion in Pharmacology is concerned with new developments in antimicrobial drugs and covers innovative strategies for dealing with...
This special issue of Current Opinion in Pharmacology is concerned with new developments in antimicrobial drugs and covers innovative strategies for dealing with microbial infection in the age of multi-antibiotic resistance. Despite widespread fears that many infectious diseases may become untreatable, disruptive innovations are in the process of being discovered and developed that may go some way to leading the fight-back against the rising threat. Natural products, quorum sensing inhibitors, biofilm disruptors, gallium-based drugs, cyclodextrin inhibitors of pore-forming toxins, anti-fungals that deal with biofilms, and light based antimicrobial strategies are specifically addressed. New non-vertebrate animal models of infection may facilitate high-throughput screening (HTS) of novel anti-infectives.
Topics: Animals; Anti-Infective Agents; Biomedical Research; Drug Discovery; Drug Resistance, Microbial; Drug Resistance, Multiple; Humans; Inventions; Quorum Sensing
PubMed: 24012294
DOI: 10.1016/j.coph.2013.08.012 -
PLoS Computational Biology May 2024Multi-drug combinations to treat bacterial populations are at the forefront of approaches for infection control and prevention of antibiotic resistance. Although the...
Multi-drug combinations to treat bacterial populations are at the forefront of approaches for infection control and prevention of antibiotic resistance. Although the evolution of antibiotic resistance has been theoretically studied with mathematical population dynamics models, extensions to spatial dynamics remain rare in the literature, including in particular spatial evolution of multi-drug resistance. In this study, we propose a reaction-diffusion system that describes the multi-drug evolution of bacteria based on a drug-concentration rescaling approach. We show how the resistance to drugs in space, and the consequent adaptation of growth rate, is governed by a Price equation with diffusion, integrating features of drug interactions and collateral resistances or sensitivities to the drugs. We study spatial versions of the model where the distribution of drugs is homogeneous across space, and where the drugs vary environmentally in a piecewise-constant, linear and nonlinear manner. Although in many evolution models, per capita growth rate is a natural surrogate for fitness, in spatially-extended, potentially heterogeneous habitats, fitness is an emergent property that potentially reflects additional complexities, from boundary conditions to the specific spatial variation of growth rates. Applying concepts from perturbation theory and reaction-diffusion equations, we propose an analytical metric for characterization of average mutant fitness in the spatial system based on the principal eigenvalue of our linear problem, λ1. This enables an accurate translation from drug spatial gradients and mutant antibiotic susceptibility traits to the relative advantage of each mutant across the environment. Our approach allows one to predict the precise outcomes of selection among mutants over space, ultimately from comparing their λ1 values, which encode a critical interplay between growth functions, movement traits, habitat size and boundary conditions. Such mathematical understanding opens new avenues for multi-drug therapeutic optimization.
Topics: Anti-Bacterial Agents; Models, Biological; Drug Resistance, Multiple, Bacterial; Computational Biology; Bacteria; Computer Simulation; Drug Resistance, Multiple; Evolution, Molecular; Humans
PubMed: 38820350
DOI: 10.1371/journal.pcbi.1012098 -
Cancer Reports (Hoboken, N.J.) Dec 2022The acquisition of resistance to chemotherapy is a major hurdle in the successful application of cancer therapy. Several anticancer approaches, including chemotherapies,... (Review)
Review
BACKGROUND
The acquisition of resistance to chemotherapy is a major hurdle in the successful application of cancer therapy. Several anticancer approaches, including chemotherapies, radiotherapy, surgery and targeted therapies are being employed for the treatment of cancer. However, cancer cells reprogram themselves in multiple ways to evade the effect of these therapies, and over a period of time, the drug becomes inactive due to the development of multi-drug resistance (MDR). MDR is a complex phenomenon where malignant cells become insensitive to anticancer drugs and attain the ability to survive even after several exposures of anticancer drugs. In this review, we have discussed the molecular and cellular paradigms of multidrug resistance in cancer.
RECENT FINDINGS
An Extensive research in cancer biology revealed that drug resistance in cancer is the result of perpetuated intracellular and extracellular mechanisms such as drug efflux, drug inactivation, drug target alteration, oncogenic mutations, altered DNA damage repair mechanism, inhibition of programmed cell death signaling, metabolic reprogramming, epithelial mesenchymal transition (EMT), inherent cell heterogeneity, epigenetic changes, redox imbalance, or any combination of these mechanisms. An inevitable cross-link between inflammation and drug resistance has been discussed. This review provided insight molecular mechanism to understand the vulnerabilities of cancer cells to develop drug resistance.
CONCLUSION
MDR is an outcome of interplays between multiple intricate pathways responsible for the inactivation of drug and development of resistance. MDR is a major obstacle in regimens of successful application of anti-cancer therapy. An improved understanding of the molecular mechanism of multi drug resistance and cellular reprogramming can provide a promising opportunity to combat drug resistance in cancer and intensify anti-cancer therapy for the upcoming future.
Topics: Humans; Drug Resistance, Neoplasm; Drug Resistance, Multiple; Neoplasms; Antineoplastic Agents; Drug Delivery Systems
PubMed: 33052041
DOI: 10.1002/cnr2.1291 -
Revista Espanola de Quimioterapia :... Sep 2022The indiscriminate and massive antibiotic use in the clinical practice and in agriculture or cattle during the past few decades has produced a serious world health... (Review)
Review
The indiscriminate and massive antibiotic use in the clinical practice and in agriculture or cattle during the past few decades has produced a serious world health problem that entails high morbidity and mortality: the antibiotic multi-drug resistance. In 2017 and 2019, the World Health Organization published a list of urgent threats and priorities in the context of drug resistance, which only included Gram-negative bacteria and specially focused on carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, as well as carbapenem and third generation cephalosporin-resistant Enterobacteriaceae. This scenario emphasizes the need of developing and testing new antibiotics from different families, such as new beta-lactams, highlighting cefiderocol and its original mechanism of action; new beta-lactamase inhibitors, with vaborbactam or relebactam among others; new quinolones such as delafloxacin, and also omadacycline or eravacycline, as members of the tetracycline family. The present work reviews the importance and impact of Gram-negative bacterial infections and their resistance mechanisms, and analyzes the current therapeutic paradigm as well as the role of new antibiotics with a promising future in the era of multi and pan-drug resistance.
Topics: Animals; Anti-Bacterial Agents; Carbapenems; Cattle; Cephalosporins; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests; Quinolones; Tetracyclines; beta-Lactamase Inhibitors; beta-Lactams
PubMed: 36193979
DOI: 10.37201/req/s02.01.2022