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Mechanisms of antibiotic resistance

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195268 Year: Pages: 224 DOI: 10.3389/978-2-88919-526-8 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Antibiotics represent one of the most successful forms of therapy in medicine. But the efficiency of antibiotics is compromised by the growing number of antibiotic-resistant pathogens. Antibiotic resistance, which is implicated in elevated morbidity and mortality rates as well as in the increased treatment costs, is considered to be one of the major global public health threats (www.who.int/drugresistance/en/) and the magnitude of the problem recently prompted a number of international and national bodies to take actions to protect the public (http://ec.europa.eu/dgs/health_consumer/docs/road-map-amr_en.pdf: http://www.who.int/drugresistance/amr_global_action_plan/en/; http://www.whitehouse.gov/sites/default/files/docs/carb_national_strategy.pdf). Understanding the mechanisms by which bacteria successfully defend themselves against the antibiotic assault represent the main theme of this eBook published as a Research Topic in Frontiers in Microbiology, section of Antimicrobials, Resistance, and Chemotherapy. The articles in the eBook update the reader on various aspects and mechanisms of antibiotic resistance. A better understanding of these mechanisms should facilitate the development of means to potentiate the efficacy and increase the lifespan of antibiotics while minimizing the emergence of antibiotic resistance among pathogens.

Antifungal Drug Discovery: New Theories and New Therapies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199501 Year: Pages: 136 DOI: 10.3389/978-2-88919-950-1 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Fungal infections such as candidoses can range from superficial mucous membrane infection to life-threatening systemic mycoses. Candida infections are a significant clinical problem globally due to rapid rise in compromised host populations including HIV/AIDS, organ transplant recipients and patients on chemotherapy. In addition, sharp increase in aging populations which are susceptible to fungal infections is expected in next few decades. Antifungal drugs are relatively difficult to develop compared to the antibacterial drugs owing to the eukaryotic nature of the cells. Therefore, only a handful of antifungal agents are currently available to treat the myriad of fungal infections. Moreover, rising antifungal resistance and host-related adverse reactions have limited the antifungal arsenal against fungal pathogens. In this research topic, we tried to update the theoretical aspects pertaining to the antifungal drug discovery i.e. proposed novel mechanisms, new drug targets and pathways. In addition, invited authors explored the new antifungal drugs derived from natural and synthetic sources which are currently under development. Contributors were encouraged to bring new insight into the antifungal drug discovery. We hope the reader may arrive at a general consensus on the possible strategies to combat ever increasing ubiquitous fungal infection in this new century.

Les derniers jours de la Troisième République à Tahiti, 1938-1940

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ISBN: 9782854300635 9782854301106 Year: Language: French
Publisher: Société des Océanistes
Added to DOAB on : 2017-10-11 09:56:05
License: OpenEdition licence for Books

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The Global Challenge Posed by the Multiresistant International Clones of Bacterial Pathogens

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452170 Year: Pages: 291 DOI: 10.3389/978-2-88945-217-0 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2017-10-13 14:57:01
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Multiresistant bacterial pathogens pose a serious problem worldwide making the appropriate treatment of patients with healthcare-associated infections a challenge. The spread of antibiotic resistance is either mediated by mobile genetic elements (MGEs) or the dissemination of genetically-related groups of pathogens, “high-risk clonal complexes”. Interestingly most multiresistant healthcare-associated bacteria command just a few dominant international clonal complexes causing infections in various geographical areas. It is of utmost importance to identify the determinants associated with and promoting the spread of antibiotic resistance and the dissemination of these multiresistant pathogens. The Topic comprises mostly of population and epidemiological studies investigating antibiotic resistance mechanisms, MGEs and the impact of antibiotic resistance, and the production of virulence factors on the clonal dynamics of a diverse range of bacterial species. Though, the exploration of the mechanisms governing clonal dynamics and the dissemination of antibiotic resistance will remain a salient issue for a considerable time to come we believe that the papers published in the Topic have usefully contributed to the better understanding of some of the processes involved and supplement papers investigating the “non-bacterial” constituents of clonal mobility, like proper medical practice and compliance with hygienic standards.

Bad Bugs in the XXIst Century: Resistance Mediated by Multi-Drug Efflux Pumps in Gram-Negative Bacteria

Authors: --- --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199310 Year: Pages: 193 DOI: 10.3389/978-2-88919-931-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2016-01-19 14:05:46
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The discovery of antibiotics represented a key milestone in the history of medicine. However, with the rise of these life-saving drugs came the awareness that bacteria deploy defence mechanisms to resist these antibiotics, and they are good at it. Today, we appear at a crossroads between discovery of new potent drugs and omni-resistant superbugs. Moreover, the misuse of antibiotics in different industries has increased the rate of resistance development by providing permanent selective pressure and, subsequently, enrichment of multidrug resistant pathogens. As a result, antimicrobial resistance has now become an urgent threat to public health worldwide (http://www.who.int/drugresistance/documents/surveillancereport/en/). The development of multidrug resistance (MDR) in an increasing number of pathogens, including Pseudomonas, Acinetobacter, Klebsiella, Salmonella, Burkholderia, and other Gram-negative bacteria is a most severe issue. Membrane efflux pump complexes of the Resistance-Nodulation-cell Division (RND) superfamily play a key role in the development of MDR in these bacteria. RND pumps, together with other transporters, contribute to intrinsic and acquired resistance to most, if not all, of the antimicrobial compounds available in our drug arsenal. Given the enormous drug polyspecificity of MDR efflux pumps, studies on their mechanism of action are extremely challenging, and this has negatively impacted both the development of new antibiotics that are able to evade these efflux pumps as well as the design of pump inhibitors. The collection of articles in this eBook, published as a Research Topic in Frontiers in Microbiology, section of Antimicrobials, Resistance, and Chemotherapy, aims to update the reader about the latest advances on the structure and function of RND efflux transporters, their roles in the overall multidrug resistance phenotype of Gram-negative pathogens, and on strategies to inhibit their activities. A deeper understanding of the mechanisms by which RND efflux pumps, alone or synergistically with other efflux pumps, are able to limit the concentration of antimicrobial compounds inside the bacterial cell, may pave the way for new, more directed, inhibitor and antibiotic design to ultimately overcome antimicrobial resistance by Gram-negatives.

Genomics and Effectomics of the Crop Killer Xanthomonas

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199020 Year: Pages: 158 DOI: 10.3389/978-2-88919-902-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany
Added to DOAB on : 2016-01-19 14:05:46
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Phytopathogenic bacteria of the Xanthomonas genus cause severe diseases on hundreds of host plants, including economically important crops, such as bean, cabbage, cassava, citrus, hemp, pepper, rice, sugarcane, tomato or wheat. Diseases occurring in nature comprise bacterial blight, canker, necrosis, rot, scald, spot, streak or wilt. Xanthomonas spp. are distributed worldwide and pathogenic and nonpathogenic strains are essentially found in association to plants. Some phytopathogenic strains are emergent or re-emergent and, consequently, dramatically impact agriculture, economy and food safety. During the last decades, massive efforts were undertaken to decipher Xanthomonas biology. So far, more than one hundred complete or draft genomes from diverse Xanthomonas species have been sequenced (http://www.xanthomonas.org), thus providing powerful tools to study genetic determinants triggering pathogenicity and adaptation to plant habitats. Xanthomonas spp. employ an arsenal of virulence factors to invade its host, including extracellular polysaccharides, plant cell wall-degrading enzymes, adhesins and secreted effectors. In most xanthomonads, type III secretion (T3S) system and secreted effectors (T3Es) are essential to bacterial pathogenicity through the inhibition of plant immunity or the induction of plant susceptibility (S) genes, as reported for Transcription Activation-Like (TAL) effectors. Yet, toxins can also be major virulence determinants in some xanthomonads while nonpathogenic Xanthomonas species do live in sympatry with plant without any T3S systems nor T3Es. In a context of ever increasing international commercial exchanges and modifications of the climate, monitoring and regulating pathogens spread is of crucial importance for food security. A deep knowledge of the genomic diversity of Xanthomonas spp. is required for scientists to properly identify strains, to help preventing future disease outbreaks and to achieve knowledge-informed sustainable disease resistance in crops. This Research Topic published in the ‘Plant Biotic Interactions’ section of Frontiers in Plant Science and Frontiers in Microbiology aims at illustrating several of the recent achievements of the Xanthomonas community. We collected twelve manuscripts dealing with comparative genomics or T3E repertoires, including five focusing on TAL effectors which we hope will contribute to advance research on plant pathogenic bacteria.

Multidrug resistance in Cancer: Pharmacological Strategies from Basic Research to Clinical Issues

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196159 Year: Pages: 99 DOI: 10.3389/978-2-88919-615-9 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology --- Science (General) --- Therapeutics
Added to DOAB on : 2016-08-16 10:34:25
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More than 40 years ago, the observation that doxorubicin-resistant tumor cells were cross-resistant to several structurally different anticancer agents was the first step in the discovery of P-glycoprotein (P-gp). P-gp belongs to the superfamily of ATP-binding cassette (ABC) transporters;its overexpression has become a therapeutic target for overcoming multidrug resistance in tumors. However, P-gp is also expressed in cells of normal tissues where it plays a physiological role, by protecting them from the toxic effects of xenobiotics. Also, ABCB1 gene polymorphisms may influence the response to anticancer drugs substrate of P-gp. Several strategies to overcome P-gp tumor drug resistance have been suggested. P-gp 'circumvention’ is the most explored and is based on the coadministration of anticancer agents and pump inhibitors (P-gp modulators). Despite the positive findings obtained in preclinical studies, results of clinical trials are not yet successful and clinical research is still ongoing. Other investigational approaches have been studied (e.g. P-gp targeting antibodies, use of antisense strategies or transcriptional regulators targeting ABCB1 gene expression) but their use is still circumscribed to the preclinical setting. A further approach is represented by the encapsulation of P-gp substrate anticancer drugs into liposomes or nanoparticles. This strategy has shown higher efficacy in tumor previously treated with the free drug. The reasons explaining the increased efficacy of liposomal/nanoparticle-based drugs in Pgp-overexpressing tumors include the coating with specific surfactants, the composition changes in the plasma membrane microdomains where P-gp is embedded, the direct impairment of P-gp catalytic mechanisms exerted by specific component of the liposomal shell, but are not yet fully understood. A second strategy to overcome P-gp tumor drug resistance is represented by exploiting the P-gp presence. Actually, P-gp-overexpressing cells show increased sensitivity (collateral sensitivity) to some drugs (e.g. verapamil, narcotic analgesics) and to some investigational compounds (e.g. NSC73306). P-gp-overexpressing cell are hypersensitive to reactive oxygen species, to agents perturbing the energetic metabolic pathways, changing the membrane compositions, reducing the efflux of endogenous toxic catabolites. However, the mechanisms explaining collateral sensitivity have not been fully elucidated. Another approach to exploit P-gp is represented by ABCB1 gene transfer to transform bone marrow progenitor cells into a drug resistant state which may allow conventional or higher doses of anticancer drug substrates of P-gp to be administered safely after transplantation. More recently the development and introduction in the clinics of anticancer drugs which are not substrates of P-gp (e.g. new microtubule modulators, topoisomerase inhibitors) has provided a new and promising strategy to overcome P-gp tumor drug resistance (P-gp 'evasion'). This ‘research topic’ issue aims at exploding the above mentioned matters, in particular by: -retracing the history of the first researches on P-gp - describing the physiological role of P-gp - describing the molecular basis, structural features and mechanism of action of P-gp - describing diagnostic laboratory methods useful to determine the expression of P-gp and its transporter function - describing strategies to overcome tumor drug resistance due to P-gp and other ABC transporters - indicating novel approaches to overcome P-gp multidrug resistance, ranging from basic research studies to pre-clinical/clinical studies.

This Cannot Happen Here: Integration and Jewish Resistance in the Netherlands, 1940-1945

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ISBN: 9789089645838 Year: DOI: 10.26530/OAPEN_617737 Language: English
Publisher: Amsterdam University Press
Subject: Law
Added to DOAB on : 2016-10-05 11:01:16
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In this book Ben Braber answers the question how the integration of Jews into Dutch society influenced Jewish resistance during the German occupation of the Netherlands in the second world war. This study highlights the social position of Jews and their group characteristics, but also reviews other factors that determined what forms Jewish resistance took such as personal character and individual circumstance.This is the first comprehensive study of this subject in the English language of Jewish resistance in the Netherlands. It offers a new perspective on Jews during the Holocaust and counters the prejudice about Jews failing to resist persecution.&#xD;&#xD;This book is also relevant for today's multi-ethnical society. It is a case study about the hampered integration of a minority, in particular how people in this group react when they are forcefully segregated and persecuted, while thinking "this cannot happen here".

René Pleven

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ISBN: 9782868471291 9782753523708 Year: Language: French
Publisher: Presses universitaires de Rennes
Added to DOAB on : 2017-03-22 17:19:00
License: OpenEdition licence for Books

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Avec cette première biographie, les multiples volets de l'action de ce grand notable républicain sont restitués dans leur contexte historique. Disparu en 1993, René Pleven, homme politique d'origine bretonne, a en effet occupé le devant de la scène, de la Deuxième Guerre mondiale au milieu des années 1970. Le choix de la France libre en juin 1940 est un tournant décisif pour l'ancien homme d'affaires qui s'affirme comme le pilier indispensable et le vrai n°2 du général de Gaulle. Par la suite...

Advances and Applications of Nano-antimicrobial Treatments

ISBN: 9783038423805 9783038423812 Year: Pages: 150 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Chemistry (General)
Added to DOAB on : 2017-04-13 12:58:27
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Nowadays, great concerns are associated with the resistance demonstrated by many microorganisms towards the conventional antibiotic therapies. The failure of traditional antimicrobials, and the increasing healthcare costs, have encouraged scientific research and the development of novel antimicrobial agents. Particularly, there is a great deal of interest in nanotechnologies and in antibacterial products obtained through the incorporation of antibacterial agents or the deposition of antibacterial coatings for prevention of biofilm-associated infections.The main focus of the forthcoming Special Issue is, therefore, to present the most recent efforts in scientific research in the development of advanced antimicrobial materials, with special attention to nature-inspired antimicrobial agents and antimicrobials nanomaterials and nanocoatings. For this purpose, we intend to collect original research articles and reviews on the synthesis and characterization of antimicrobial agents, as well as on the development of antimicrobial products for different applications.

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