Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multidrug-resistant tuberculosis (MDR-TB) caused by Mycobacterium tuberculosis resistant to both isoniazid and rifampicin with or without resistance to other drugs is among the most worrisome elements of the pandemic of antibiotic resistance. Globally, about three per cent of all newly diagnosed patients have MDR-TB. The proportion is higher in patients who have previously received antituberculosis treatment reflecting the failure of programmes designed to ensure complete cure of patients with tuberculosis. While host genetic factors may probably contribute, incomplete and inadequate treatment is the most important factor leading to the development of MDR-TB. The definitive diagnosis of MDR-TB is difficult in resource poor low income countries because of non-availability of reliable laboratory facilities. Efficiently run tuberculosis control programmes based on directly observed treatment, short-course (DOTS) policy is essential for preventing the emergence of MDR-TB. Management of MDR-TB is a challenge which should be undertaken by experienced clinicians at centres equipped with reliable laboratory service for mycobacterial culture and in vitro sensitivity testing as it requires prolonged use of expensive second-line drugs with a significant potential for toxicity. Judicious use of drugs, supervised individualised treatment, focussed clinical, radiological and bacteriological follow up, use of surgery at the appropriate juncture are key factors in the successful management of these patients. In certain areas, currently available programme approach may not be adequate and innovative approaches such as DOTS-plus may have to be employed to effectively control MDR-TB.
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PMID:Multidrug-resistant tuberculosis. 1552 Apr 86

234 isolates of Mycobacterium tuberculosis obtained from 1000 suspected cases of tuberculosis reporting at National Institute of Communicable Disease, Delhi for laboratory investigation between Jan 2001 to August 2002 were subjected to invitro drug sensitivity test against the first line drugs (Isoniazid, Streptomycin, Rifampicin, Ethambutol and Thiacetazone) by proportion method using Lowenstein Jensen (LJ) media. Out of 234 isolates of Mycobacterium tuberculosis, 142 were from cases of untreated tuberculosis, whereas only 92 isolates were from treated cases of tuberculosis. An initial drug resistance of 21.83% was seen against INH, 9.85% against Streptomycin, 15.49% against Rifampicin, 4.22% against ethambutol and 2.11% to thiacetazone. Multidrug resistance (MDR-i.e. Resistance to both INH and Rifampicin) was seen in 11.97% of isolates. 4(2.8%) isolates were found to be resistant to all drugs tested. A much higher level of acquired resistance was seen the figures being 61.95% for INH, 53.36% for rifampicin, 35.86% for streptomycin, 20.65% for ethambutol and 10.86% for thiacetazone. Avery high acquired MDR to the tune of 42.39% was seen. 24(26%) isolates were found to be resistant to all drugs tested. No significant difference were observed in the drug resistance pattern between pulmonary and extrapulmonary cases of tuberculosis in both initial and acquired drug resistance category.
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PMID:Drug resistance in tuberculosis in Delhi: a 2 year profile (2001--2002). 1556 52

Mycobacterium (M.) tuberculosis is the most common individual causative agent of infectious disease in the world. It is responsible for 26% of preventable deaths in adulthood. Because the number of new cases grows at an annual rate of 2%, in 1993 WHO proclaimed tuberculosis a global health problem. The immediate cause for this was coinfection with causative agents of tuberculosis and human immunodeficiency virus, and spread of resistant and multiresistant strains of M. tuberculosis (MDR TB). It is estimated that 50 million people are infected with resistant strains of M. tuberculosis. Tuberculosis has emerged as a major public health problem for its high mortality (50%-80%) in the first 4-16 weeks of the disease and 100 times more expensive therapy for drug-resistant than for drug-susceptible tuberculosis. Mycobacteriologic laboratories play a fundamental role in the detection, combat and control of tuberculosis, especially in preventing the spread of drug-resistant tuberculosis. In this connection, there is an increased need of a rapid and reliable determination of the susceptibility of isolated strains of M. tuberculosis to the first- and second-line antituberculotic drugs.
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PMID:[Drug-resistant tuberculosis: resistance mechanisms and drug susceptibility of Mycobacterium tuberculosis]. 1570 Jun 89

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality due to a bacterial pathogen. According to the 2004 Global TB Control Report of the World Health Organization, there are 300,000 new cases per year of multi-drug resistant strains (MDR-TB), defined as resistant to isoniazid and rifampicin, and 79% of MDR-TB cases are now "super strains," resistant to at least three of the four main drugs used to treat TB. Thus there is a need for the development of effective new agents to treat TB. The shikimate pathway is an attractive target for the development of antimycobacterial agents because it has been shown to be essential for the viability of M. tuberculosis, but absent from mammals. The M. tuberculosis aroG-encoded 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (mtDAHPS) catalyzes the first committed step in this pathway. Here we describe the PCR amplification, cloning, and sequencing of aroG structural gene from M. tuberculosis H37Rv. The expression of recombinant mtDAHPS protein in the soluble form was obtained in Escherichia coli Rosetta-gami (DE3) host cells without IPTG induction. An approximately threefold purification protocol yielded homogeneous enzyme with a specific activity value of 0.47U mg(-1) under the experimental conditions used. Gel filtration chromatography results demonstrate that recombinant mtDAHPS is a pentamer in solution. The availability of homogeneous mtDAHPS will allow structural and kinetics studies to be performed aiming at antitubercular agents development.
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PMID:DAHP synthase from Mycobacterium tuberculosis H37Rv: cloning, expression, and purification of functional enzyme. 1572 68

Little is known about the intracellular events that occur following the initial inhibition of Mycobacterium tuberculosis by the first-line antituberculosis drugs isoniazid (INH) and ethambutol (EMB). Understanding these pathways should provide significant insights into the adaptive strategies M. tuberculosis undertakes to survive antibiotics. We have discovered that the M. tuberculosis iniA gene (Rv 0342) participates in the development of tolerance to both INH and EMB. This gene is strongly induced along with iniB and iniC (Rv 0341 and Rv 0343) by treatment of Mycobacterium bovis BCG or M. tuberculosis with INH or EMB. BCG strains overexpressing M. tuberculosis iniA grew and survived longer than control strains upon exposure to inhibitory concentrations of either INH or EMB. An M. tuberculosis strain containing an iniA deletion showed increased susceptibility to INH. Additional studies showed that overexpression of M. tuberculosis iniA in BCG conferred resistance to ethidium bromide, and the deletion of iniA in M. tuberculosis resulted in increased accumulation of intracellular ethidium bromide. The pump inhibitor reserpine reversed both tolerance to INH and resistance to ethidium bromide in BCG. These results suggest that iniA functions through an MDR-pump like mechanism, although IniA does not appear to directly transport INH from the cell. Analysis of two-dimensional crystals of the IniA protein revealed that this predicted transmembrane protein forms multimeric structures containing a central pore, providing further evidence that iniA is a pump component. Our studies elucidate a potentially unique adaptive pathway in mycobacteria. Drugs designed to inhibit the iniA gene product may shorten the time required to treat tuberculosis and may help prevent the clinical emergence of drug resistance.
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PMID:The Mycobacterium tuberculosis iniA gene is essential for activity of an efflux pump that confers drug tolerance to both isoniazid and ethambutol. 1575 3

From August to December 1998, over a period of 5 months, a cross-sectional study had been carried out in Abidjan in order to analyze the epidemiological and microbiological features of BAAR+ TB patients in situation of failure or relapse after specific treatment. We investigated 79 patients enrolled in the departments of pulmonary disease of two general hospitals in Abidjan (CHU of Cocody and Treichville) and a TB outpatients' clinic. From 45 strains of Mycobacterium obtained by culture, 33 antibiograms were performed. The rate of multi-drug-resistance (MDR-TB) was 79%. Among MDR--TB patients, those aged of 20-40 years were the most concerned age group (72%) with a clear male predominant rate (sex ratio: 3). Among them 49/79 (62%) had an educational level lower or equal to primary school standarts and most of them lived in dwellings with common yard (67%). In their medical history only 40% had tuberculosis and 2 cases of self-medication were reported. MDR--TB prevailed among patients having at first a positive bacilloscopy. No link between HIV infection and MDR--TB was found.
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PMID:[Epidemiological, clinical and biological profile of resistant or recurrent pulmonary tuberculosis in Abidjan]. 1578 67

The decision to develop a new chemical entity should not only be based on its ability to inhibit multidrug-resistant tuberculosis (MDR-TB) strains but also on its ability to enter macrophages and be active against intracellular bacteria. RBx 7644 and RBx 8700, two novel extended spectrum oxazolidinones, were investigated for their activity against sensitive and MDR isolates of Mycobacterium tuberculosis and for activity against bacteria within a macrophage cell line. RBx 8700 showed excellent in vitro activity against sensitive as well as MDR M. tuberculosis strains with MIC(50) and MIC(90) values of 0.032 and 0.25mg/L (sensitive) and 0.25 and 1.0mg/L (MDR) strains. The corresponding MIC(50) and MIC(90) values of RBx 7644, linezolid, rifampicin and isoniazid were 8 and 16; 32 and 64; 64 and 64; 64 and 64 mg/L, respectively. RBx 8700 and rifampicin were bactericidal at 0.5 and 0.25mg/L when tested intracellularly whereas linezolid reduced the count by 100-fold at a concentration of 8 mg/L. In combination studies with standard antimycobacterial drugs, RBx 8700 did not show any antagonistic effect.
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PMID:Activity of RBx 7644 and RBx 8700, new investigational oxazolidinones, against Mycobacterium tuberculosis infected murine macrophages. 1588 88

The frequency of resistance genotypes among Beijing and non-Beijing strains was compared using a reverse blot hybridization assay to detect mutations within genes associated with rifampicin (rpoB) and isoniazid (katG, inhA, and ahpC) resistance. Of the 743 Mycobacterium tuberculosis isolates, 569 (77%) belonged to Beijing family. The proportion of Beijing strains was significantly higher among MDR-TB isolates than among drug-susceptible strains (82% vs. 72%, p<0.01). Genotype analysis of the rpoB gene revealed significantly lower rates of the Ser531Leu mutation rate among Beijing vs. non-Beijing MDR-TB strains (41% vs. 66%, p<0.005). While the mutation for Ser315Thr in the katG gene was more common among Beijing vs. non-Beijing family strains (65% vs. 50%, p<0.01), the mutation rate of promoter region of the inhA gene was lower among Beijing strains compared with non-Beijing strains (14% vs. 25%, p<0.05). Reverse hybridization successfully detected over 80% of isoniazid-resistant strains and over 92% of rifampicin-resistant strains among Korean isolates. Significant differences in mutation rates in the rpoB, katG, and inhA genes between Beijing strains and non-Beijing strains could explain discrepancies in mutation rates of genotypes in different countries. Reverse hybridization was useful for rapid detection of isoniazid and rifampicin resistant strains.
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PMID:Comparison of drug resistance genotypes between Beijing and non-Beijing family strains of Mycobacterium tuberculosis in Korea. 1589 92

Almost a third of the world's population is infected with Mycobacterium tuberculosis, the organism that causes tuberculosis disease. Most of those infected never fall ill, but individuals who do can recover if they have access to effective therapies. This paper discusses certain ethical and ethnographic issues raised by cases in which patients are infected with M. tuberculosis strains resistant to at least the two most powerful drugs on which therapy is usually based. In most poor countries, people with such multidrug-resistant tuberculosis (MDR-TB) were, until very recently, considered "untreatable." In addition to being consigned to a permanent state of ill health, they were also at risk of transmitting their resistant strain to others. In this paper we discuss the logic of "cost-effectiveness," which international health policy-makers utilized to make the case that treatment of MDR-TB is not feasible in resource poor settings. These analyses, which have held sway in public health policy for many years, are flawed, we argue, because they ignore and conceal the social determinants of access to health services and often rely on assumptions rather than evidence. We propose that policies based solely on analyses of cost-effectiveness of specific interventions for individual settings can be short-sighted and, because they do not pay sufficient attention to the social, political, economic, epidemiological and pathophysiological factors influencing the production of health, will ultimately hinder progress toward effective global TB control.
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PMID:Limited good and limited vision: multidrug-resistant tuberculosis and global health policy. 1589 95

Conjugate addition of diamines to glycosyl olefinic esters 1a and 1b followed by reduction of resulting bis-glycosyl beta-amino esters (2-7 and 14-19) with lithium aluminium hydride led to the respective glycosyl amino alcohols (8-13 and 20-25) in moderate to good yields. All the compounds were evaluated for antitubercular activity against Mycobacterium tuberculosis H(37)Ra and H(37)Rv. Few of the compounds exhibited antitubercular activity with MIC as low as 6.25-3.12microg/mL in virulent and avirulent strains. Compound 13 was found to be active against MDR strain and showed mild protection in mice.
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PMID:Synthesis and antitubercular activities of bis-glycosylated diamino alcohols. 1595 3


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