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ACS Infectious Diseases Nov 2023Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One... (Review)
Review
Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One such WHO-critical group pathogen is . The extensive and inappropriate treatments for infections have led from multi-drug resistance (MDR) to extensive drug resistance (XDR). The synergy between efflux-mediated systems and outer membrane proteins (OMPs) may favor MDR in . Differential expression of the efflux system and OMPs (influx) and positional mutations are the factors that can be correlated to the development of drug resistance. Insights into the mechanism of influx and efflux of antibiotics can aid in developing a structurally stable molecule that can be proficient at escaping from the resistance loops in . Understanding the strategic responsibilities and developing policies to address the surge of drug resistance at the national, regional, and global levels are the needs of the hour. In this Review, we attempt to aggregate all the available research findings and delineate the resistance mechanisms by dissecting the involvement of OMPs and efflux systems. Integrating major OMPs and the efflux system's differential expression and positional mutation in may provide insight into developing strategic therapies for one health application.
Topics: Membrane Proteins; Membrane Transport Proteins; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Salmonella
PubMed: 37910638
DOI: 10.1021/acsinfecdis.3c00408 -
Archives of Microbiology Mar 2023Infections by ESKAPE (Enterococcus sp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens... (Review)
Review
Infections by ESKAPE (Enterococcus sp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens cause major concern due to their multi-drug resistance (MDR). The ESKAPE pathogens are frequently linked to greater mortality, diseases, and economic burden in healthcare worldwide. Therefore, the use of plants as a natural source of antimicrobial agents provide a solution as they are easily available and safe to use. These natural drugs can also be enhanced by incorporating silver nanoparticles and combining them with existing antibiotics. By focussing the attention on the ESKAPE organisms, the MDR issue can be addressed much better.
Topics: Drug Resistance, Multiple, Bacterial; Humans; Plants; Anti-Bacterial Agents; Metal Nanoparticles; Silver; Plant Extracts; Gram-Positive Bacteria; Gram-Negative Bacteria; Cross Infection
PubMed: 36917278
DOI: 10.1007/s00203-023-03455-6 -
Molecular Biology Reports Aug 2021Malignant tumors have become the most dangerous disease in recent years. Chemotherapy is the most effective treatment for this disease; however, the problem of drug... (Review)
Review
BACKGROUND
Malignant tumors have become the most dangerous disease in recent years. Chemotherapy is the most effective treatment for this disease; however, the problem of drug resistance has become even more common, which leads to the poor prognosis of patients suffering from cancers. Thus, necessary measures should be taken to address these problems at the earliest. Many studies have demonstrated that drug resistance is closely related to the abnormal expressions of long non-coding RNAs (lncRNAs).
METHODS AND RESULTS
This review aimed to summarize the molecular mechanisms underlying the association of lncRNAs and the development of drug resistance and to find potential strategies for the clinical diagnosis and treatment of cancer drug resistance. Studies showed that lncRNAs can regulate the expression of genes through chromatin remodeling, transcriptional regulation, and post-transcriptional processing. Furthermore, lncRNAs have been reported to be closely related to the occurrence of malignant tumors. In summary, lncRNAs have gained attention in related fields during recent years. According to previous studies, lncRNAs have a vital role in several different types of cancers owing to their multiple mechanisms of action. Different mechanisms have different functions that could result in different consequences in the same disease.
CONCLUSIONS
LncRNAs closely participated in cancer drug resistance by regulating miRNA, signaling pathways, proteins, cancer stem cells, pro- and ant-apoptosis, and autophagy. lncRNAs can be used as biomarkers of the possible treatment target in chemotherapy, which could provide solutions to the problem of drug resistance in chemotherapy in the future.
Topics: Biomarkers, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasms; RNA, Long Noncoding
PubMed: 34333735
DOI: 10.1007/s11033-021-06603-7 -
International Journal of Pharmaceutics Aug 2022Multi-drug resistance (MDR) in breast cancer poses a great threat to chemotherapy. The expression and function of the ATP binding cassette (ABC) transporter are the...
Multi-drug resistance (MDR) in breast cancer poses a great threat to chemotherapy. The expression and function of the ATP binding cassette (ABC) transporter are the major cause of MDR. Herein, a linear polyethylene glycol (PEI) conjugated with dicyandiamide, which called polymeric metformin (PolyMet), was successfully synthesized as a simple and biocompatible polymer of metformin. PolyMet showed the potential to reverse MDR by inhibiting the efflux of the substrate of ATP-binding cassette (ABC) transporter from DOX resistant MCF-7 cells (MCF-7/DOX). To test its MDR reversing effect, PolyMet was combined with DOX to treat mice carrying MCF-7/DOX xenografts. In order to decrease the toxicities of DOX and delivery PolyMet and DOX to tumor at the same time, PolyMet was complexed with poly-γ-glutamic acid-doxorubicin (PGA-DOX) electrostatically at the optimal ratio of 2:3, which were further coated with lipid membrane to form lipid/PolyMet-(PGA-DOX) nanoparticles (LPPD). The particle size of LPPD was 165.8 nm, and the zeta potential was +36.5 mV. LPPD exhibited favorable cytotoxicity and cellular uptake in MCF-7/DOX. Meanwhile, the bioluminescence imaging and immunohistochemical analysis indicated that LPPD effectively conquered DOX-associated MDR by blocking ABC transporters (ABCB1 and ABCC1) via PolyMet. Remarkably, LPPD significantly inhibited the tumor growth and lowered the systemic toxicity in a murine MCF-7/DOX tumor model. This is the first time to reveal that PolyMet can enhance the anti-tumor efficacy of DOX by dampening ABC transporters and activating the AMPK/mTOR pathway, which is a promising strategy for drug-resistant breast cancer therapy.
Topics: Animals; Female; Humans; Mice; Adenosine Triphosphate; ATP-Binding Cassette Transporters; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; MCF-7 Cells; Metformin; Polyethylene Glycols
PubMed: 35750278
DOI: 10.1016/j.ijpharm.2022.121931 -
Current Clinical Pharmacology 2015Tuberculosis is one of the leading causes of morbidity and mortality worldwide. Current treatment has several challenges, such as multi-drug resistance, extensively... (Review)
Review
Tuberculosis is one of the leading causes of morbidity and mortality worldwide. Current treatment has several challenges, such as multi-drug resistance, extensively drug-resistance and HIV co-infection. Problems related to patients, treatment and health care system also contribute negatively to this panel. This review summarizes the main obstacles causing in the treatment of tuberculosis and discusses several strategies to improve the treatment.
Topics: Animals; Antitubercular Agents; Drug Resistance, Multiple, Bacterial; HIV Infections; Humans; Treatment Outcome; Tuberculosis
PubMed: 26338175
DOI: 10.2174/1574884708666131229124215 -
The Journal of Hospital Infection May 2022Antimicrobial resistance in Staphylococcus aureus imposes a high disease burden. Both phenotypic and genotypic monitoring are key to understanding and containing...
BACKGROUND
Antimicrobial resistance in Staphylococcus aureus imposes a high disease burden. Both phenotypic and genotypic monitoring are key to understanding and containing emerging resistant strains.
AIM
Phenotypic monitoring of emerging resistance in S. aureus and correlation of priority strain phenotypes with whole-genome sequencing (WGS) findings.
METHODS
Antimicrobial susceptibility test results of >40,000 isolates from 213 participating hospitals from 2011 to 2019 were exported from the national Japan Nosocomial Infections Surveillance (JANIS) database. Longitudinal and geographic distribution and prevalence of distinct multi-drug resistance phenotypes ('resistance profiles') of S. aureus were examined among hospitals and prefectures. We further conducted a genome sequence analysis of strains with specific resistance profiles of concern.
FINDINGS
The overall prevalence of meticillin-resistant S. aureus (MRSA) decreased from 40.3% to 35.1% from 2011 to 2019. However, among dozens of S. aureus resistance profiles, only one profile of a type of MRSA, exhibited a statistically significant increase in inpatient frequency, exceeding 10% during the nine years. This MRSA profile showed resistance to oxacillin, erythromycin and levofloxacin. Analysis of WGS results of S. aureus isolates with this phenotype revealed that most belonged to clonal complex 8, and all carried SCCmec IV, typical of community-acquired MRSA.
CONCLUSION
Tracking distinct resistance profiles deepened our understanding of the overall decrease in MRSA and led to recognition of the emergence of a new resistance phenotype. This study provides a model for future epidemiological research on antimicrobial resistance correlating multi-drug resistance phenotypes with selective genome sequencing, which can be applied to other bacterial species.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple; Drug Resistance, Multiple, Bacterial; Humans; Japan; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Phenotype; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35202748
DOI: 10.1016/j.jhin.2022.02.011 -
Anti-cancer Agents in Medicinal... Nov 2017Multidrug resistance occurs when a tumor develops resistance to multiple chemotherapeutic drugs, which may include antitumor drugs with different chemical structures and... (Review)
Review
Multidrug resistance occurs when a tumor develops resistance to multiple chemotherapeutic drugs, which may include antitumor drugs with different chemical structures and mechanisms. Multidrug resistance limits the treatment effects of antitumor drugs, and is the main cause of chemotherapy failure. Multidrug resistance is caused by numerous factors including changes in ATP-binding cassette transporters, target proteins, detoxification, deoxyribonucleic acid repair, drug metabolic enzymes, and signal pathways of apoptosis. Clinical research indicates that natural products have great potential to treat tumors and reverse multidrug resistance. Natural products, which often have multiple targets, could play an important role in tumor treatment, have beneficial effects on tumor inhibition, improve symptoms, reduce radiotherapy and chemotherapy side effects, enhance immunity, and prolong survival. Because natural products often have few adverse reactions and less drug resistance, the antitumor activities of natural products have attracted extensive research. We aimed to review the basic research and clinical application of natural products in the reversal of multidrug resistance.
Topics: Animals; Antineoplastic Agents; Biological Products; Cell Death; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Neoplasms
PubMed: 29034843
DOI: 10.2174/1871520617666171016105704 -
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 -
Phytochemistry May 2016Stephania tetrandra and other related species of Menispermaceae form the major source of the bisbenzylisoquinoline alkaloid - tetrandrine. The plant is extensively... (Review)
Review
Stephania tetrandra and other related species of Menispermaceae form the major source of the bisbenzylisoquinoline alkaloid - tetrandrine. The plant is extensively referenced in the Chinese Pharmacopoeia for its use in the Chinese medicinal system as an analgesic and diuretic agent and also in the treatment of hypertension and various other ailments, including asthma, tuberculosis, dysentery, hyperglycemia, malaria, cancer and fever. Tetrandrine, well-known to act as a calcium channel blocker, has been tested in clinical trials and found effective against silicosis, hypertension, inflammation and lung cancer without any toxicity. Recently, the efficacy of tetrandrine was tested against Mycobaterium tuberculosis, Candida albicans, Plasmodium falciparum and Ebola virus. Tetrandrine's pharmacological property has been proved to be through its action on different signalling pathways like reactive oxygen species, enhanced autophagic flux, reversal of multi drug resistance, caspase pathway, cell cycle arrest and by modification of calcium channels. The present review summarises current knowledge on the synthesis, distribution, extraction, structural elucidation, pharmacological properties and the mechanism of action of tetrandrine. Future perspectives in the clinical use of tetrandrine as a drug are also considered.
Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Benzylisoquinolines; Candida albicans; Drug Resistance, Multiple; Ebolavirus; Hemorrhagic Fever, Ebola; Mycobacterium tuberculosis; Plasmodium falciparum; Stephania tetrandra
PubMed: 26899361
DOI: 10.1016/j.phytochem.2016.02.005 -
Nanomedicine : Nanotechnology, Biology,... Feb 2022Multidrug resistance (MDR) in cancer chemotherapy is a growing concern for medical practitioners. P-glycoprotein (P-gp) overexpression is one of the major reasons for... (Review)
Review
Multidrug resistance (MDR) in cancer chemotherapy is a growing concern for medical practitioners. P-glycoprotein (P-gp) overexpression is one of the major reasons for multidrug resistance in cancer chemotherapy. The P-gp overexpression in cancer cells depends on several factors like adenosine triphosphate (ATP) hydrolysis, hypoxia-inducible factor 1 alpha (HIF-1α), and drug physicochemical properties such as lipophilicity, molecular weight, and molecular size. Further multiple exposures of anticancer drugs to the P-gp efflux protein cause acquired P-gp overexpression. Unique structural and functional characteristics of nanotechnology-based drug delivery systems provide opportunities to circumvent P-gp mediated MDR. The primary mechanism behind the nanocarrier systems in P-gp inhibition includes: bypassing or inhibiting the P-gp efflux pump to combat MDR. In this review, we discuss the role of P-gp in MDR and highlight the recent progress in different nanocarriers to overcome P-gp mediated MDR in terms of their limitations and potentials.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms
PubMed: 34775061
DOI: 10.1016/j.nano.2021.102494