1,721,078 research outputs found

    Mycobacterium tuberculosis: drug resistance and future perspectives

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    TB is still a global health problem. The selection and spread of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis strains represents a threat for global TB control. The reappearance of TB has driven an increased interest in understanding the mechanisms of drug action and drug resistance, which could provide a significant contribution in the development of new antimicrobials. In this article, the authors describe the mode of action and the resistance mechanisms of the principal first- and second-line antitubercular agents, namely isoniazid, ethionamide, ethambutol, D-cycloserine, rifamycins, fluoroquinolones, streptomycin, linezolid and pyrazinamide. A brief outline of the seven drugs in clinical development is reported, showing how the development of new TB drugs is still required

    NITROREDUCTASE NfnB FROM Mycobacterium smegmatis

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    The present invention relates to a screening method for the identification of new nitrobenzothiazinone drugs for the treatment of tuberculosis, which are not or are slowly transformed and inactivated by nitroreductase. The use of the nitroreductase NfnB from M. smegmatis in cancer therapy, and in bioremediation are comprised as well

    AN EFFECTIVE NEW DRUG TARGET FOR THE TREATMENT OF TUBERCULOSIS

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    The present invention allows a screening method for identifying novel drugs for the treatment of tuberculosis as well as a diagnostic method for identifying clinical strains that are resistant to these novel drugs

    Trends in discovery of new drugs for tuberculosis therapy

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    After the introduction of isoniazid and rifampicin, the second one discovered in the Lepetit Research Laboratories (Milan, Italy), under the supervision of Professor Piero Sensi, tuberculosis (TB) was considered an illness of the past. Unfortunately, this infectious disease is still a global health fear, due to the multidrug-resistant Mycobacterium tuberculosis and extensively circulating drug-resistant strains, as well as the unrecognized TB transmission, especially in regions with high HIV incidence. In the last few years, new antitubercular molecules appeared on the horizon both in preclinical and clinical stage of evaluation. In this review, we focus on a few of them and on their mechanism of action. Two new promising drug targets, DprE1 and MmpL3, are also discussed

    Gut Microbial Signatures in Sporadic and Hereditary Colorectal Cancer

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    Colorectal cancer (CRC) is the fourth most common cause of cancer-related death and the third most common cancer in the world. Depending on the origin of the mutation, colorectal carcinomas are classified as sporadic or hereditary. Cancers derived from mutations appearing during life, affecting individual cells and their descendants, are called sporadic and account for almost 95% of the CRCs. Less than 5% of CRC cases result from constitutional mutations conferring a very high risk of developing cancer. Screening for hereditary-related cancers is offered to individuals at risk for hereditary CRC, who have either not undergone genetic evaluation or have uncertain genetic test results. In this review, we briefly summarize the main findings on the correlation between sporadic CRC and the gut microbiota, and we specifically focus on the few evidences about the role that gut microorganisms have on the development of CRC hereditary syndromes. The characterization of a gut microbiota associated with an increased risk of developing CRC could have a profound impact for prevention purposes. We also discuss the potential role of the gut microbiota as therapeutic treatment

    Mycobacterium tuberculosis efflux pumps: an update

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    The selection and diffusion of Mycobacterium tuberculosis multidrug-resistant (MDR-TB), extensively drug-resistant (XDR-TB) and, more recently, totally drug-resistant (TDR) strains constitute a serious threat for tuberculosis global control. Mycobacteria, such as M. tuberculosis and Mycobacterium smegmatis, possess several putative drug efflux transporters, but their role in resistance is still a hard topic and needs to be further investigated as resistance to several drugs is usually the result of the combination of independent mutations in genes encoding either the drug target or the enzymes involved in drug activation. However, as the genetic basis of resistance to some antitubercular agents is not fully known for some clinical isolates, we cannot rule out an efflux mechanism in these strains. Several drug efflux transporters have been described in mycobacteria as responsible for resistance to aminoglycosides, chloramphenicol, fluoroquinolones, isoniazid, linezolid, rifampicin, tetracycline and other compounds but most of them were isolated in laboratory rather than in hospitals

    Genomic analysis of zinc homeostasis in Mycobacterium tuberculosis

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    Zn is involved in several cellular processes and the maintenance of cellular Zn status is essential for life. Therefore, an improved understanding of zinc acquisition and metabolism is of great significance, especially in important pathogens such as Mycobacterium tuberculosis whose capacity to survive within the phagosomal compartment is fundamental for its pathogenicity. A crucial point is the bacterial ability to compete with the host for nutrients, and the acquisition of metal ions, such as iron and zinc
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