The solvent-free reaction of o-phenylenediamine (I) with the carboxylic acids (II) leads to higher product yields compared to the Phillips method for instance. Some of the products, e.g. (IIIa), (IIIb), and (Va), exhibit a high tuberculostatic activity. -(FOKS*, H.; PANCECHOWSKA-KSEPKO, D.; KUZMIERKIEWICZ, W.; ZWOLSKA, Z.; AUGUSTYNOWICZ-KOPEC, E.; JANOWIEC, M.; Chem. Heterocycl. Compd. (N. Y.) 42 (2006) 5, 611-614; Dep. Org. Chem., Med. Univ. Gdansk, PL-80-416 Gdansk, Pol.; Eng.) -H. Haber 03-110
Diagnozowanie gruźlicy oparte na bakteryjnym czynniku etiologicznym ma już ponad 100-letnią historię. Nowoczesna terapia rozpoczęła się jednak dopiero po II wojnie światowej wraz z odkryciem i wprowadzeniem do terapii leków przeciwprątkowych. Przez dziesięciolecia grupy międzynarodowych specjalistów pracowały nad ustaleniem najskuteczniejszych schematów leczenia [...]
Introduction: A major role in the development of resistance of Mycobacterium tuberculosis to isoniazid (INH) is attributed to mutations in the katG gene coding for the catalase/peroxidase, an enzyme required for obtaining a pharmacologically active form of the drug. Analysis of mutations in the katG gene in M. tuberculosis strains may contribute to the development of reliable and rapid tests for detection of INH resistance. The aim of the study was to identify and characterize mutations in the katG gene in multidrug-resistant M. tuberculosis clinical isolates. Material and Methods: The study included 46 strains of M. tuberculosis, recovered from MDR-TB patients in Poland in 2004. Mutations in the katG gene were detected by comparing DNA sequences with the corresponding sequence of a wild-type reference laboratory strain (M. tuberculosis H37Rv). The obtained results were interpreted in the context of MIC values of INH and catalase activity of the strains tested. Results: A total of 43 (93%) strains contained mutations in the katG gene. The most frequently observed were mutations at codon 315, found in 34 (74%) strains. Mutations at other codons were rare: 4 strains contained mutations at codon 463, 2 at codon 131 and another 2 at codon 234. Mutations at codons 68, 91, 101, 126, 128 and 194 were found in single strains only. Two strains, for which no mutations at codon 315 of the katG gene were identified, had a unique translation termination mutation, which would invariably result in polypeptide truncation leading to the generation of dysfunctional catalase polypeptides. Both these strains presented the highest MIC values for INH (80 and 100 μg/mL) and showed a complete loss of catalase activity. For the remaining 41 strains with katG mutations, the MICs of INH were within the range 0.2–10 μg/mL. Thirty-six (88%) of those strains retained their catalase activity. Conclusions: Mutations at codon 315 within the katG gene, depending on their type might be useful for the prediction of INH resistance. Whereas the missense mutations do not affect the catalase activity or the level of INH resistance, the nonsense mutations result in high-level resistance to INH and a total loss of catalase activity.
The capacities of differentiation of Mycobacterium bovis BCG from other members of M. tuberculosis complex species using PCR-RFLP, multiplex PCR, and PCR-based genomic deletion analysis approaches were compared. In the study, mycobacteria isolated from patients suspected of adverse events following vaccination with BCG, primarily classified according presence of RD1 marker as virulent and avirulent mycobacteria, were used. The PCR-based genomic deletion analysis was found the best option for mycobacteria diagnostics improvement, as it was capable precisely differentiate virulent and avirulent mycobacteria or virulent species of M. tuberculosis complex. The routine confirmation of mycobacteria species in the cases of adverse events following BCG vaccination is highly expected, especially in clinical practice of patients with primary immunodeficiency.
Introduction: The control of tuberculosis (TB) requires methods for rapid detection and tracing sources of infection, so that further transmission can be arrested. Recent developments in molecular biology have resulted in techniques that allow prompt identification and tracking specific strains of M. tuberculosis as they spread through the population. Most of these techniques take advantage of M. tuberculosis DNA polymorphism and are based on various repetitive DNA elements as genetic markers. Each method yields strain-specific genetic profiles (fingerprints). Strains showing identical fingerprints are referred to as clustered and are usually associated with recent transmission, whereas strains whose fingerprints are unique are presumed to represent remote transmission, a reactivation of infection acquired in the distant past. Material and methods: In recent years, spoligotyping has become one of the most widely used genotyping method for epidemiological studies of TB. Spoligotyping is a PCR-based method allowing to analyze strain-dependent polymorphisms observed in spacer sequences present within the direct repeat (DR) genomic region of M. tuberculosis complex strains. Spoligotyping provides some important advantages over other genotyping techniques. These are simplicity, rapidity, high reproducibility and stability of the results, with the latter being expressed in a simple digital pattern, readily named and databased, and the ability to perform spoligotyping directly on clinical samples, without the need for prior culture. However, spoligotyping has relatively low discriminatory capacity, which makes it necessary to use secondary fingerprinting methods to prove clonality between isolates. Results: The aim of this study was to evaluate the usefulness of spoligotyping in epidemiological investigations of TB by analyzing 16 isoniazid-resistant M. tuberculosis strains isolated from patients with pulmonary TB in the central region of Poland. A total of 11 distinct spoligopatterns were obtained. 9 isolates were represented by a unique pattern, whereas 7 were clustered in 2 groups of 5 and 2 isolates, respectively. When compared with an international spoligodatabase SpolDB4, 13 isolates shared already described spoligotypes, whereas 3 did not match any existing spoligopattern in database and were defined as orphans. Spoligotyping overestimated the number of clustered isolates in one of its two clusters when compared to IS6110 Mtb1/ /Mtb2 PCR. Strains clustered using the latter method were assumed to be closely epidemiologically related. Conclusions: This report demonstrates the utility of spoligotyping as an initial screening technique, to be supplemented by another typing method of greater discriminatory power, such as the IS6110 Mtb1/Mtb2 PCR in order to better recognize the epidemiological links between TB patients.
Tuberculosis (TB) continues to be one of the most challenging public health problems in the world. An important contributor to the global burden of the disease is the emergence and spread of drug-resistant and particularly multidrug-resistant Mycobacterium tuberculosis strains (MDR), defined as being resistant to at least isoniazid and rifampicin. In recent years, the introduction of different DNA-based molecular typing methods has substantially improved the knowledge of the epidemiology of TB. The purpose of this study was to employ a combination of two PCR-based genotyping methods, namely spoligotyping and IS6110-Mtb1/Mtb2 PCR to investigate the clonal relatedness of MDR M. tuberculosis clinical isolates recovered from pulmonary TB patients from Poland. Among the 50 isolates examined, 28 (56%) were clustered by spoligotyping, whereas IS6110-Mtb1/Mtb2 PCR resulted in 16 (32%) clustered isolates. The isolates that clustered in both typing methods were assumed to be clonally related. A two-step strategy consisting of spoligotyping as a first-line test, performed on the entire pool of isolates, and IS6110-Mtb1/Mtb2 PCR typing as a confirmatory subtyping method, performed only within spoligotype-defined clusters, is an efficient approach for determining clonal relatedness among M. tuberculosis clinical isolates.
Introduction: The retrospective analysis of frequency of drug resistant tuberculosis XDR (XDR = MDR + resistance to: fluoroquinolones + amikacin and/or capreomycin) in Poland have been tested. Material and methods: Pattern of resistance to first, second and third line drugs has been tested among new and treated patients. The total number of 10,913 Mycobacterium tuberculosis strains isolated from the same number of the patients surveyed in 1997–2004 in WHO programme Drug resistance surveillance countrywide study. Results: One HIV-negative patient (43 years old men) was infected by XDR (0.4% among new and treated MDR cases). Molecular analysis of the XDR strain by spoligotyping has been shown the T11558 cluster. Three others tuberculosis patients living in the same region of Poland excreted the Mycobacterium tuberculosis strains belonged to the same T11558 cluster, but they had not pattern of XDR resistance. In the same T11558 molecular cluster 13/15—87% strains have been isolated from polish patients. Conclusions: In Poland Mycobacterium tuberculosis resistance to fluoroquinolones, capreomycin and amikacine among MDR strains has been observed very rarely.
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