9 research outputs found

    Contribution of Efflux to the Emergence of Isoniazid and Multidrug Resistance in Mycobacterium tuberculosis

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    Multidrug resistant (MDR) tuberculosis is caused by Mycobacterium tuberculosis resistant to isoniazid and rifampicin, the two most effective drugs used in tuberculosis therapy. Here, we investigated the mechanism by which resistance towards isoniazid develops and how overexpression of efflux pumps favors accumulation of mutations in isoniazid targets, thus establishing a MDR phenotype. The study was based on the in vitro induction of an isoniazid resistant phenotype by prolonged serial exposure of M. tuberculosis strains to the critical concentration of isoniazid employed for determination of drug susceptibility testing in clinical isolates. Results show that susceptible and rifampicin monoresistant strains exposed to this concentration become resistant to isoniazid after three weeks; and that resistance observed for the majority of these strains could be reduced by means of efflux pumps inhibitors. RT-qPCR assessment of efflux pump genes expression showed overexpression of all tested genes. Enhanced real-time efflux of ethidium bromide, a common efflux pump substrate, was also observed, showing a clear relation between overexpression of the genes and increased efflux pump function. Further exposure to isoniazid resulted in the selection and stabilization of spontaneous mutations and deletions in the katG gene along with sustained increased efflux activity. Together, results demonstrate the relevance of efflux pumps as one of the factors of isoniazid resistance in M. tuberculosis. These results support the hypothesis that activity of efflux pumps allows the maintenance of an isoniazid resistant population in a sub-optimally treated patient from which isoniazid genetically resistant mutants emerge. Therefore, the use of inhibitors of efflux should be considered in the development of new therapeutic strategies for preventing the emergence of MDR-TB during treatment

    Sustainable Mineral Resources Management: From Regional Mineral Resources Exploration to Spatial Contamination Risk Assessment of Mining

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    Wide-spread environmental contamination associated with historic mining in Europe has triggered social responses to improve related environmental legislation, the environmental assessment and management methods for the mining industry. Mining has some unique features such as natural background contamination associated with mineral deposits, industrial activities and contamination in the three-dimensional subsurface space, problem of long-term remediation after mine closure, problem of secondary contaminated areas around mine sites, land use conflicts and abandoned mines. These problems require special tools to address the complexity of the environmental problems of mining-related contamination. The objective of this paper is to show how regional mineral resources mapping has developed into the spatial contamination risk assessment of mining and how geological knowledge can be transferred to environmental assessment of mines. The paper provides a state-of-the-art review of the spatial mine inventory, hazard, impact and risk assessment and ranking methods developed by national and international efforts in Europe. It is concluded that geological knowledge on mineral resources exploration is essential and should be used for the environmental contamination assessment of mines. Also, sufficient methodological experience, knowledge and documented results are available, but harmonisation of these methods is still required for the efficient spatial environmental assessment of mine contamination.JRC.H.1-Water Resource

    Option s for Compiling an Inventory of Mining Waste Sites throughout Europe

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    Abstract not availableJRC.H-Institute for environment and sustainability (Ispra

    Validation of the GenoType MTBDRplus assay for diagnosis of multidrug resistant tuberculosis in South Vietnam.

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    Contains fulltext : 124360.pdf (publisher's version ) (Open Access)BACKGROUND: To control multidrug resistant tuberculosis (MDR-TB), the drug susceptibility profile is needed to guide therapy. Classical drug susceptibility testing (DST) may take up to 2 to 4 months. The GenoType MTBDRplus test is a commercially available line-probe assay that rapidly detects Mycobacterium tuberculosis (MTB) complex, as well as the most common mutations associated with rifampin and isoniazid resistance.We assessed sensitivity and specificity of the assay by using a geographically representative set of MTB isolates from the South of Vietnam. METHODS: We re-cultured 111 MTB isolates that were MDR, rifampin-resistant or pan-susceptible according to conventional DST and tested these with the GenoType MTBDRplus test. RESULTS: By conventional DST, 55 strains were classified as MDR-TB, four strains were rifampicin mono-resistant and 52 strains were susceptible to all first-line drugs. The sensitivity of the GenoType MTBDRplus was 93.1% for rifampicin, 92.6% for isoniazid and 88.9% for the combination of both; its specificity was 100%. The positive predictive value of the GenoType MTBDRplus test for MDR-TB was 100% and the negative predictive value 90.3%. CONCLUSIONS: We found a high specificity and positive predictive value of the GenoType MTBDRplus test for MDR-TB which merits its use in the MDR-TB treatment program in Vietnam

    Environmental Informatics for Solid and Hazardous Waste Management: Advances, Challenges, and Perspectives

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    Environmental informatics has experienced extraordinarily rapid progress in the past decade and has made an invaluable contribution to planning, design, and operations for waste management. In many cases, however, the roles of these information technologies have been limited to stand-alone projects without synergistic effects. This article presents a holistic view and an in-depth discussion of environmental informatics applied to solid and hazardous waste management from the onset to the present status, and to future trends aiming to advance the management potential. With regard to building, maintaining, and developing knowledge-based or artificial intelligence systems, the spectrum of environmental informatics for solid and hazardous waste management can be classified into five categories: database system, geographical information system, decision support system, expert system, and integrated environmental information system. Supporting technologies in the integrated environmental information system can be further divided into five classes in a logical order to enhance understanding: data acquisition, data communication, data and knowledge storage, data mining and knowledge discovery, and data and knowledge utilization. This critical review article may help create sustainable development strategies from a local solution to global opportunities that will elevate environmental informatics to a new level in dealing with more complex problems and large-scale applications for integrated solid and hazardous waste management. © 2013 Copyright Taylor and Francis Group, LLC
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