embCAB Sequence Variation Among Ethambutol-Resistant Mycobacterium Tuberculosis Isolates Without embB306 Mutation

Mechanisms of resistance to ethambutol in Mycobacterium tuberculosis remain inadequately described. Although there is mounting evidence that mutations of codon 306 in embB play a key role, a significant number of phenotypically ethambutol-resistant strains do not carry mutations in this codon. Here, other mutations in the embCAB operon are suggested to be involved in resistance development

Genomic Diversity among Drug Sensitive and Multidrug Resistant Isolates of Mycobacterium tuberculosis with Identical DNA Fingerprints

complex (MTBC), the causative agent of tuberculosis (TB), is characterized by low sequence diversity making this bacterium one of the classical examples of a genetically monomorphic pathogen. Because of this limited DNA sequence variation, routine genotyping of clinical MTBC isolates for epidemiological purposes relies on highly discriminatory DNA fingerprinting methods based on mobile and repetitive genetic elements. According to the standard view, isolates exhibiting the same fingerprinting pattern are considered direct progeny of the same bacterial clone, and most likely reflect ongoing transmission or disease relapse within individual patients.We generated 23.9 million (K-1) and 33.0 million (K-2) paired 50 bp purity filtered reads corresponding to a mean coverage of 483.5 fold and 656.1 fold respectively. Compared with the laboratory strain H37Rv both Beijing isolates shared 1,209 SNPs. The two Beijing isolates differed by 130 SNPs and one large deletion. The susceptible isolate had 55 specific SNPs, while the MDR variant had 75 specific SNPs, including the five known resistance-conferring mutations. isolates exhibiting identical DNA fingerprinting patterns can harbour substantial genomic diversity. Because this heterogeneity is not captured by traditional genotyping of MTBC, some aspects of the transmission dynamics of tuberculosis could be missed or misinterpreted. Furthermore, a valid differentiation between disease relapse and exogenous reinfection might be impossible using standard genotyping tools if the overall diversity of circulating clones is limited. These findings have important implications for clinical trials of new anti-tuberculosis drugs

High Resolution Discrimination of Clinical Mycobacterium tuberculosis Complex Strains Based on Single Nucleotide Polymorphisms

Recently, the diversity of the Mycobacterium tuberculosis complex (MTBC) population structure has been described in detail. Based on geographical separation and specific host pathogen co-evolution shaping MTBC virulence traits, at least 20 major lineages/genotypes have evolved finally leading to a clear influence of strain genetic background on transmissibility, clinical presentation/outcome, and resistance development. Therefore, high resolution genotyping for characterization of strains in larger studies is mandatory for understanding mechanisms of host-pathogen-interaction and to improve tuberculosis (TB) control. Single nucleotide polymorphisms (SNPs) represent the most reliable markers for lineage classification of clinical isolates due to the low levels of homoplasy, however their use is hampered either by low discriminatory power or by the need to analyze a large number of genes to achieve higher resolution. Therefore, we carried out de novo sequencing of 26 genes (approx. 20000 bp per strain) in a reference collection of MTBC strains including all major genotypes to define a highly discriminatory gene set. Overall, 161 polymorphisms were detected of which 59 are genotype-specific, while 13 define deeper branches such as the Euro-American lineage. Unbiased investigation of the most variable set of 11 genes in a population based strain collection (one year, city of Hamburg, Germany) confirmed the validity of SNP analysis as all strains were classified with high accuracy. Taken together, we defined a diagnostic algorithm which allows the identification of 17 MTBC phylogenetic lineages with high confidence for the first time by sequencing analysis of just five genes. In conclusion, the diagnostic algorithm developed in our study is likely to open the door for a low cost high resolution sequence/SNP based differentiation of the MTBC with a very high specificity. High throughput assays can be established which will be needed for large association studies that are mandatory for detailed investigation of host-pathogen-interaction during TB infection

A CLASSIFICATION OF GOETHITE MINERALS BASED ON THE MÖSSBAUER BEHAVIOUR

Les effets de la réduction de la taille des grains dans des échantillons naturels de goethite sont décrits, comme ils se manifestent en spectroscopie Mössbauer, en diffraction de rayons X et en thermogravimétrie. Nous avons trouvé une corrélation entre la dimension moyenne des grains et le type de formation des minerais. Nous proposons une classification dans laquelle les minerais, selon la forme générale de leur spectre Mössbauer, se présentent en trois classes qui correspondent aux différents types de formation.In this paper grain size effects in mineralogical goethite samples are described, as they appear in Mössbauer spectroscopy, X-ray diffraction, and thermogravimetric analysis. A correlation is laid between the grain size and the type of formation. According to the general shape of their Mössbauer spectra, the naturally occuring goethite samples can be classified in three groups, corresponding to different types of formation

Handelbare Umweltlizenzen zur Verminderung von VOC-Emissionen aus nicht genehmigungsbeduerftigen Anlagen Konzeption eines Pilotprojektes fuer die Autoreparaturlackierung

The objective is to investigate if a system of tradable environmental permits to reduce VOC-Emissions for facilities not requiring official approval for operation is applicable, and wether such a system offers benefits in practice. A general tradeable permit model and a pilot project for VOC abatement among approval exempt auto paint and body shops were designed. Both are ready for approval. The legal framework for the conception was the EU directive on the limitation of VOC emissions from solvent-using industries, which as an alternative to a command-and-control approach explicitly allows the use of a tradable permit model. The concept came about through a mediation approach: the model was designed by Prognos and B, S, S. Volkswirtschaftliche Beratung in direct co-operation with the German Ministry for the Environment, the Federal Environmental Agency and the paintjob repair shops related trade associations BFL and VdL. The model found is a detailed and very much praxis-oriented approach which offers - compared to traditional environmental law - significant savings: due to our calculations savings of about 11.000 DM for only four small enterprises are offered by tradable permits in comparison with a command-and-control approach. Finally possibilities to transfer this model to other sectors which are not subject to authorisations were analysed. A transfer can be recommended for the sectors: machinery manufacturing, large vehicle manufacturing, electrical/electronics products, iron, tin and metal processing as well as the wood and furniture industry. (orig.)Available from TIB Hannover: RN 8422(1998,23) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Umwelt, Naturschutz und Reaktorsicherheit, Bonn (Germany)DEGerman