共查询到20条相似文献,搜索用时 15 毫秒
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The acquisition of vancomycin resistance by Gram-positive bacteria and carbapenem resistance by Gram-negative bacteria has rendered some hospital-acquired pathogens impossible to treat. The resistance mechanisms employed are sophisticated and very difficult to overcome. Unless alternative treatment regimes are initiated soon, our inability to treat totally resistant bacteria will halt other developments in medicine. In the community, Gram-positive bacteria responsible for pneumonia could become totally resistant leading to increased mortality from this common infection, which would have a more immediate impact on our current lifestyles. 相似文献
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Md Mahmudul Islam H.M. Adnan Hameed Julius Mugweru Chiranjibi Chhotaray Changwei Wang Yaoju Tan Jianxiong Liu Xinjie Li Shouyong Tan Iwao Ojima Wing Wai Yew Eric Nuermberger Gyanu Lamichhane Tianyu Zhang 《遗传学报》2017,44(1):21-37
Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance. 相似文献
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Chemotherapy is the main strategy for the treatment of cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance. The resistance can be intrinsic or acquired. The resistance phenotype is associated with the tumor cells that gain a cross-resistance to a large range of drugs that are structurally and functionally different. Multidrug resistance arises via many unrelated mechanisms, such as overexpression of energy-dependent efflux proteins, decrease in uptake of the agents, increase or alteration in drug targets, modification of cell cycle checkpoints, inactivation of the agents, compartmentalization of the agents, inhibition of apoptosis and aberrant bioactive sphingolipid metabolism. Exact elucidation of resistance mechanisms and molecular and biochemical approaches to overcome multidrug resistance have been a major goal in cancer research. This review comprises the mechanisms guiding multidrug resistance in cancer chemotherapy and also touches on approaches for reversing the resistance. 相似文献
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Multidrug resistance mechanisms: drug efflux across two membranes 总被引:25,自引:0,他引:25
A set of multidrug efflux systems enables Gram-negative bacteria to survive in a hostile environment. This review focuses on the structural features and the mechanism of major efflux pumps of Gram-negative bacteria, which expel from the cells a remarkably broad range of antimicrobial compounds and produce the characteristic intrinsic resistance of these bacteria to antibiotics, detergents, dyes and organic solvents. Each efflux pump consists of three components: the inner membrane transporter, the outer membrane channel and the periplasmic lipoprotein. Similar to the multidrug transporters from eukaryotic cells and Gram-positive bacteria, the inner membrane transporters from Gram-negative bacteria recognize and expel their substrates often from within the phospholipid bilayer. This efflux occurs without drug accumulation in the periplasm, implying that substrates are pumped out across the two membranes directly into the medium. Recent data suggest that the molecular mechanism of the drug extrusion across a two-membrane envelope of Gram-negative bacteria may involve the formation of the membrane adhesion sites between the inner and the outer membranes. The periplasmic components of these pumps are proposed to cause a close membrane apposition as the complexes are assembled for the transport. 相似文献
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Microbial toxins in plant-pathogen interactions: Biosynthesis,resistance mechanisms,and significance
In the history of phytopathology, microbial toxins have been the objects of extensive studies as possible pathogenicity or virulence factors for the producer pathogens. The recent development of molecular genetic techniques provided an experimental basis to thoroughly test the role of these secondary metabolites in pathogenesis. Some of them did prove to be highly associated with disease initiation or enhanced virulence in certain plant-pathogen interactions. In this review, we describe recent progresses in the field of plant-pathogen interactions focusing on two toxins; i.e., tabtoxin from Pseudomonas syringae and trichothecenes from Fusarium and other fungi. These microbial toxins have convincingly been shown to play causal roles in plant disease development. Studies on the biosynthesis and resistance mechanisms of these producers are outlined, and the significance of this knowledge is discussed in relation to practical applications in agriculture. 相似文献
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Kwang-Woo Jung Sangyong Lim Yong-Sun Bahn 《Journal of microbiology (Seoul, Korea)》2017,55(7):499-507
Organisms living in extreme environments have evolved a wide range of survival strategies by changing biochemical and physiological features depending on their biological niches. Interestingly, organisms exhibiting high radiation resistance have been discovered in the three domains of life (Bacteria, Archaea, and Eukarya), even though a naturally radiationintensive environment has not been found. To counteract the deleterious effects caused by radiation exposure, radiation- resistant organisms employ a series of defensive systems, such as changes in intracellular cation concentration, excellent DNA repair systems, and efficient enzymatic and non-enzymatic antioxidant systems. Here, we overview past and recent findings about radiation-resistance mechanisms in the three domains of life for potential usage of such radiationresistant microbes in the biotechnology industry. 相似文献
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The inhibition of protein kinases has gained general acceptance as an effective approach to treat a wide range of cancers. However, in many cases, prolonged administration of kinase inhibitors often leads to acquired resistance, and the therapeutic effect is subsequently diminished. The wealth of recent studies using biochemical, kinetic, and structural approaches have revealed the molecular basis for the clinically observed resistance. In this review, we highlight several of the most common molecular mechanisms that lead to acquired resistance to kinase inhibitors observed with the cAbl (cellular form of the Abelson leukemia virus tyrosine kinase) and the type III receptor tyrosine kinase cKit, including a newly identified mechanism resulting from accelerated kinase activation caused by mutations in the activation loop. Strategies to overcome the loss of drug sensitivity that represents a challenge currently facing the field and the emerging approaches to circumvent resistance are discussed. 相似文献
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《Critical reviews in biochemistry and molecular biology》2013,48(4):295-309
The inhibition of protein kinases has gained general acceptance as an effective approach to treat a wide range of cancers. However, in many cases, prolonged administration of kinase inhibitors often leads to acquired resistance, and the therapeutic effect is subsequently diminished. The wealth of recent studies using biochemical, kinetic, and structural approaches have revealed the molecular basis for the clinically observed resistance. In this review, we highlight several of the most common molecular mechanisms that lead to acquired resistance to kinase inhibitors observed with the cAbl (cellular form of the Abelson leukemia virus tyrosine kinase) and the type III receptor tyrosine kinase cKit, including a newly identified mechanism resulting from accelerated kinase activation caused by mutations in the activation loop. Strategies to overcome the loss of drug sensitivity that represents a challenge currently facing the field and the emerging approaches to circumvent resistance are discussed. 相似文献
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A major problem in chemotherapy of cancer patients is drug resistance as well as unpredictable response to treatment. During chemotherapy, multiple alterations of genetics and epigenetics that contribute to chemoresistance take place, eventually impacting on disease outcome. A more complex picture of the mechanisms of drug resistance is now emerging through application of high-throughput proteomics technology. We have entered an exciting time where proteomics are being applied to characterize the mechanisms of drug resistance, and to identify biomarkers for predicting response to chemotherapy, thereby leading to personalized therapeutic strategies of cancer patients. Comparative proteomics have identified a large number of differentially expressed proteins associated with chemoresistance. Although roles and mechanisms of such proteins in chemoresistance need to be further proved, at least some of them may be potential biomarkers for predicting chemotherapeutic response. Herein, we review the recent advancements on proteomic investigation of chemoresistance in human cancer, and emphasize putative biomarkers for predicting chemotherapeutic response and possible mechanisms of chemoresistance identified through proteomic approaches. Suggested avenues for future work are discussed. 相似文献
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Antibiotic-resistant enterococci: the mechanisms and dynamics of drug introduction and resistance 总被引:7,自引:0,他引:7
Enterococci possess a vast array of mechanisms to resist the lethal effects of most antimicrobial drugs currently approved for therapeutic use in humans, thus presenting a considerable therapeutic challenge. This review summarizes current concepts regarding the mechanisms of resistance, as well as the emergence, proliferation, and epidemiology of resistant enterococci. 相似文献
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Combating bacteria and drug resistance by inhibiting mechanisms of persistence and adaptation 总被引:1,自引:0,他引:1
Antibiotics have revolutionized the treatment of infectious disease but have also rapidly selected for the emergence of resistant pathogens. Traditional methods of antibiotic discovery have failed to keep pace with the evolution of this resistance, which suggests that new strategies to combat bacterial infections may be required. An improved understanding of bacterial stress responses and evolution suggests that in some circumstances, the ability of bacteria to survive antibiotic therapy either by transiently tolerating antibiotics or by evolving resistance requires specific biochemical processes that may themselves be subject to intervention. Inhibiting these processes may prolong the efficacy of current antibiotics and provide an alternative to escalating the current arms race between antibiotics and bacterial resistance. Though these approaches are not clinically validated and will certainly face their own set of challenges, their potential to protect our ever-shrinking arsenal of antibiotics merits their investigation. This Review summarizes the early efforts toward this goal. 相似文献