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La tuberculose, une maladie infectieuse causée par Mycobacterium tuberculosis ou bacille de Koch, est connue depuis l’Antiquité. Dans les années 60-70, il y a eu un réel espoir d'éradication avec l'avènement des antituberculeux et du vaccin BCG. Le traitement de première ligne de la tuberculose comprend une association de quatre antibiotiques efficaces. L'instauration de cette tétra-thérapie était nécessaire pour éviter le phénomène de sélection de résistance car le bacille de Koch a tendance à muter fréquemment. Depuis quelques années, on constate que la diminution du nombre de cas de tuberculose n'est pas aussi drastique que ce qui avait été prédit par l'OMS. Parallèlement à cela, on assiste à une multiplication du nombre de cas de tuberculose multi résistante et même de tuberculose ultrarésistante. Cela peut s'expliquer notamment par le manque de compliance des patients au traitement. En effet, le traitement s'étale sur minimum six mois alors que les patients ressentent déjà une amélioration des symptômes après quelques semaines, ce qui les pousse à stopper le traitement plus tôt. La situation est critique et nécessite un besoin urgent de nouveaux médicaments. En 2005, un nouvel antituberculeux très prometteur est découvert. Il s'agit de la bédaquiline qui est le premier antituberculeux à perturber le métabolisme énergétique de M tuberculosis, ce qui permet d'éviter la résistance croisée avec les antituberculeux connus. La bédaquiline a fait l'objet de procédures accélérées d'autorisation de mise sur le marché. Les quelques études font état d'une grande efficacité de cette molécule sur les souches sensibles et résistantes. Cependant, les données sur sa sécurité nécessitent des investigations supplémentaires car on a constaté une mortalité plus importante dans le groupe "bédaquiline" par rapport au groupe placebo. Dans ce travail, je vais d'une part passer en revue toutes les données disponibles dans la littérature et d'autre part, je vais discuter de la problématique de l'émergence d'une résistance vis à vis de la bédaquiline. Tuberculosis, an infectious disease caused by Mycobacterium Tuberculosis or Koch’s bacillus, has been known since Antiquity. In the 1960s and 1970 there was real hope for its eradication thanks to the discovery of anti-tuberculosis drugs and the BCG VACCINE. The usual treatment for tuberculosis involves the intake of four very efficient antibiotics. This tetra therapy is necessary to avoid selection of resistant’s variant from susceptible pathogens because Koch’s bacillus tends to mutate very easily. For several years it has been reported that the decline in the number of tuberculosis cases announced by the WHO is not significant as foreseen. At the same time we observe an increase in the number of multi-drug resistant (MDR) tuberculosis (TB) and even (pre-extensively) drug resistant (pre-XDR), tuberculosis. This can be partly explained by the non-compliance with drug therapy from patients. Actually, the treatment for tuberculosis lasts for at least six months whereas patients already feel better after some weeks, which incites them to stop their treatment too early. That’s why we had to face a critical situation which required an urgent need for new medicines. In 2005, a new anti-tuberculosis drug is discovered. This drug called bedaquiline which disturbs the energy metabolism of M. Tuberculosis and avoids cross-resistance to well-known antibiotics. An accelerated approval has been given to bedaquiline as the FDA believed that the clinical benefits of the drug should be used in the affected population. Some studies show that this molecule is highly active against drug sensitive, MDR, Pre-XDR and XDR strains of M., Tuberculosis. However, the safety profile of bedaquiline requires ongoing close scrutiny. In fact, a higher rate of mortality has been highlighted in the group treated with bedaquiline compared to the placebo group. In this work most available data on bedaquiline is also mentioned. Actually, some scientists have already tried to describe some mechanisms able to lead to a resistance to bedaquiline.
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ABC Proteins is an in-depth, up-to-date analysis of all that is known about the subject to date. It discusses and compares evolution, biology and mechanism of action of all known ABC proteins, including the first structural studies as well as clinical implications. It will be useful to anyone trying to stay abreast of the latest findings. This book is sure to become a classic and will regularly be updated.Key Features* Phylogeny and Evoloution of ABC Transporters* Fundamental Aspects of the Mechanism of Action of ABC Transporters* Prokaryote ABC Transporters* Non
ATP-binding cassette transporters. --- ABC PROTEINS --- MONOGRAPHS
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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact
adenosine --- ATP --- purinergic receptors --- purinergic signaling --- ectonucleotidases
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milk --- milk --- Dairy hygiene --- Dairy hygiene --- Bacteriology --- Bacteriology --- Atp techniques --- Atp techniques
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Energy metabolism --- cytology --- Photosynthesis --- ATP cycle --- Thermodynamique --- Forces moleculaires
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ATP --- Activated sludge --- Wastewater treatment --- biomass --- Enzyme activity --- Bioluminescence --- Bioluminescence
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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact
Science: general issues --- Pharmacology --- adenosine --- ATP --- purinergic receptors --- purinergic signaling --- ectonucleotidases --- adenosine --- ATP --- purinergic receptors --- purinergic signaling --- ectonucleotidases
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Escherichia coli --- Escherichia coli --- ATP --- ATP --- proteins --- proteins --- Enzymes --- Enzymes --- cytoplasm --- cytoplasm --- genetic engineering --- genetic engineering --- genetic maps --- genetic maps
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ATP-binding cassette transporters. --- Clinical biochemistry. --- Medical biochemistry --- Pathobiochemistry --- Pathological biochemistry --- Biochemistry --- Pathology --- ABC proteins --- ABC transporters --- ATP-binding cassette proteins --- Carrier proteins --- Membrane proteins
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