Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspergillus nidulans conidiospores contain high levels of the non-reducing disaccharide trehalose. We show that upon induction of conidiospore germination, the trehalose pool is rapidly degraded and a glycerol pool is transiently accumulated. A trehalase with an acidic pH optimum was purified from conidiospores. Characterization of the treA gene encoding this trehalase shows that it is homologous to Saccharomyces cerevisiae vacuolar acid trehalase, the product of the ATH1 gene, and to two related proteins of unknown function identified in Mycobacterium tuberculosis and Mycobacterium leprae. A. nidulans mutants that lack acid trehalase activity were constructed by gene replacement at the treA locus. Analysis of these mutants suggests that the treA gene product is localized in the conidiospore wall, is required for growth on trehalose as a carbon source, and is not involved in the mobilization of the intracellular pool of trehalose. Therefore, it is proposed that a cytoplasmic regulatory trehalase is controlling this latter process.
Mol Microbiol 1997 Apr
PMID:Molecular characterization of the Aspergillus nidulans treA gene encoding an acid trehalase required for growth on trehalose. 914 Sep 77

Tuberculosis and other mycobacterial infections are the most serious infectious diseases in terms of human fatalities. The high content of unique cell-wall lipids helps these organisms to resist antimicrobial drugs and host defences. The biosynthesis of these lipids is discussed briefly. The recent advances in recombinant DNA technology have begun to help to elucidate the nature of some of the enzymes involved in this process and the genes that encode them. Gene disruption and other molecular genetic technologies are beginning to provide new approaches to test for the biological functions of these gene products and may lead to identification of new antimycobacterial drug targets.
Mol Microbiol 1997 Apr
PMID:Biochemistry and molecular genetics of cell-wall lipid biosynthesis in mycobacteria. 915 14

The genus Mycobacterium comprises clinically important pathogens such as M. tuberculosis, which has reemerged as a major cause of morbidity and mortality world-wide especially with the emergence of multidrug-resistant strains. The use of fast-growing species such as Mycobacterium smegmatis has allowed important advances to be made in the field of mycobacterial genetics and in the study of the mechanisms of resistance in mycobacteria. The isolation of an aminoglycoside-resistance gene from Mycobacterium fortuitum has recently been described. The aac(2')-Ib gene is chromosomally encoded and is present in all isolates of M. fortuitum. The presence of this gene in other mycobacterial species is studied here and genes homologous to that of M. fortuitum have been found in all mycobacterial species studied. In this report, the cloning of the aac(2')-Ic gene from M. tuberculosis H37Rv and the aac(2')-Id gene from M. smegmatis mc(2)155 is described. Southern blot hybridizations have shown that both genes are present in all strains of this species studied to date. In addition, the putative aac(2')-Ie gene has been located in a recent release of the Mycobacterium leprae genome. The expression of the aac(2')-Ic and aac(2')-Id genes has been studied in M. smegmatis and only aac(2')-Id is correlated with aminoglycoside resistance. In order to elucidate the role of the aminoglycoside 2'-N-acetyltransferase genes in mycobacteria and to determine whether they are silent resistance genes or whether they have a secondary role in mycobacterial metabolism, the aac(2')-Id gene from M. smegmatis has been disrupted in the chromosome of M. smegmatis mc(2)155. The disruptant shows an increase in aminoglycoside susceptibility along with a slight increase in the susceptibility to lysozyme.
Mol Microbiol 1997 Apr
PMID:Aminoglycoside 2'-N-acetyltransferase genes are universally present in mycobacteria: characterization of the aac(2')-Ic gene from Mycobacterium tuberculosis and the aac(2')-Id gene from Mycobacterium smegmatis. 915 28

Specific mutations associated with resistance to streptomycin (SM) in Mycobacterium tuberculosis suggest themselves for its rapid prediction. However, as with any diagnostic test, their predictive values are dependent on their prevalences. In this report, SM resistance associated mutations in the rrs and rpsL genes of 25 SM resistant isolates from Germany and 25 SM resistant isolates from Sierra Leone were characterized and compared. Mutations in the rrs gene were infrequent in isolates from both localities (20% and 12%, respectively) and thus of limited predictive values. In contrast, rpsL mutations were found in 48% of the German isolates but only in 24% of the isolates from Sierra Leone. It is concluded that the predictive values of mutations in this gene may vary significantly with the origin of the samples under investigation.
Mol Cell Probes 1997 Apr
PMID:Geographic variation of the predictive values of genomic mutations associated with streptomycin resistance in Mycobacterium tuberculosis. 916 Mar 26

The objective of this study was to determine whether quantitative-competitive polymerase chain reaction (QC-PCR) can be used for rapid susceptibility testing of Mycobacterium tuberculosis (MTB). QC-PCR was used to determine relative amounts of mycobacterial DNA inoculated at different isoniazid (INH) concentrations. A total of six different INH-sensitive (INH-S) and five INH-resistant (INH-R) strains were inoculated in the presence of 0.0, 0.2, 1.0, and 10.0 micrograms/ml of INH. DNA was quantified using QC-PCR at Week 0 and weekly thereafter for 3 weeks. For the QC-PCR, 10-fold dilutions of control (240 bp) DNA having the same primer set as the target DNA (123 bp) were used. The amount of target DNA was estimated by using known amounts of the internal standard. For INH-S isolates there was > or = 1 log difference in DNA concentration in the presence of each INH concentration compared to that of the control within 1 to 3 weeks. In contrast, for INH-R isolates there were no apparent differences in DNA concentration between the control suspensions and those containing 0.2 and 1.0 microgram/ml INH during the 3-week incubation period. The highest INH concentration (10 micrograms/ml), however, did abolish the DNA increase seen in the other MTB suspensions. This preliminary study suggests that by using concentrations of 0.2 or 1.0 microgram/ml of INH, QC-PCR may differentiate INH-R and INH-S MTB isolates within 1 week. This method may be of particular value when applied directly to clinical specimens with varying numbers of bacilli.
Biochem Mol Med 1997 Apr
PMID:Quantitative-competitive polymerase chain reaction for rapid susceptibility testing of Mycobacterium tuberculosis to isoniazid. 916 1

The emerging awareness that diseases caused by bacterial pathogens cannot be vanquished by chemotherapy alone has recalled interest in the generation of novel vaccines. Vaccines have proven their efficacy for the bacterial pathogens that are controlled by antibodies. In contrast, satisfactory vaccines are not available for intracellular bacteria that are under the control of T lymphocytes. This review describes the T cell populations that must be activated by successful vaccines against intracellular bacteria and discusses parameters that need to be fulfilled by protective T cell antigens. These parameters include: (a) the intracellular localization of the pathogen with major effect on antigen presentation and stimulation of distinct T cell subsets and (b) the antigen display which markedly influences kinetics of T cell activation. Using tuberculosis as an example, the advantages and disadvantages of second-generation vaccine candidates are discussed.
J Mol Med (Berl) 1997 May
PMID:Antibacterial vaccines: impact of antigen handling and immune response. 918 77

Expression or possession of catalase gene may interfere with the iNOS/NO pathway in mycobacteria, hence altering their capacity to survive within macrophages. Therefore, strains of M. smegmatis with an inactive catalase-peroxidase gene (KatG), or into which the KatG gene of Mycobacterium tuberculosis had been transfected, were used to study the influence of catalase on nitric oxide (NO) production and mycobacterial survival within infected murine 1774 macrophages. High levels of nitrite (40-70 nM) were detected in IFN-gamma and LPS activated, infected murine cell culture supernatants, however, NO2- titres produced by infected murine cells did not differ between various catalase phenotype strains. Similarly, no significant difference in mycobacterial killing was also observed among the five strains of M. smegmatis tested over a 3 day infection period.
Biochem Mol Biol Int 1997 Jun
PMID:Influence of Mycobacterium tuberculosis catalase gene (KatG) expression on nitric oxide production and the intracellular growth of transfected Mycobacterium smegmatis strains within murine macrophages. 919 93

In spite of variations in the sequences of tRNAs, the genetic code (anticodon trinucleotides) is conserved in evolution. However, non-anticodon nucleotides which are species specific are known to prevent a given tRNA from functioning in all organisms. Conversely, species-specific tRNA contact residues in synthetases should also prevent cross-species acylation in a predictable way. To address this question, we investigated the relatively small tyrosine tRNA synthetase where contacts of Escherichia coli tRNA(Tyr) with the alpha2 dimeric protein have been localized by others to four specific sequence clusters on the three-dimensional structure of the Bacillus stearothermophilus enzyme. We used specific functional tests with a previously not-sequenced and not-characterized Mycobacterium tuberculosis enzyme and showed that it demonstrates species-specific aminoacylation in vivo and in vitro. The specificity observed fits exactly with the presence of the clusters characteristic of those established as important for recognition of E. coli tRNA. Conversely, we noted that a recent analysis of the tyrosine enzyme from the eukaryote pathogen Pneumocystis carinii showed just the opposite species specificity of tRNA recognition. According to our alignments, the sequences of the clusters diverge substantially from those seen with the M. tuberculosis, B. stearothermophilus and other enzymes. Thus, the presence or absence of species-specific residues in tRNA synthetases correlates in both directions with cross-species aminoacylation phenotypes, without reference to the associated tRNA sequences. We suggest that this kind of analysis can identify those synthetase-tRNA covariations which are needed to preserve the genetic code. These co-variations might be exploited to develop novel antibiotics against pathogens such as M. tuberculosis and P. carinii.
J Mol Biol 1997 May 30
PMID:Species-specific tRNA recognition in relation to tRNA synthetase contact residues. 919 96

DNA vaccines have been demonstrated to be effective in inducing protective cell-mediated immune responses in animal models of infectious disease. In order to investigate this approach for potential use as a vaccine for tuberculosis, DNA constructs encoding Mycobacterium tuberculosis antigen 85A (Ag85A) were prepared. Expression of Ag85A in mammalian cells was demonstrated by transient transfection of cells in vitro. Intramuscular injection of Ag85A DNA vaccines resulted in the generation of anti-Ag85A antibodies and robust cell-mediated immune responses, as measured by lymphoproliferation of spleen cells in vitro upon specific antigen restimulation, leading to protection in animal challenge models. Therefore, the technique of DNA vaccination is effective in inducing relevant immune responses for protection against tuberculosis and may be used to identify the protective antigens of M. tuberculosis.
Cell Mol Biol (Noisy-le-grand) 1997 May
PMID:Induction of humoral and cellular immune responses by vaccination with M. tuberculosis antigen 85 DNA. 919 82

Attachment of Mycobacterium tuberculosis organisms to alveolar macrophages (AMs) is an essential early event in primary pulmonary tuberculosis. Surfactant protein A (SP-A) is a nonimmune opsonin present in the alveolar spaces that binds carbohydrate residues such as mannose. It was hypothesized that SP-A attaches to M. tuberculosis and serves as a ligand between M. tuberculosis and AMs. [125I]SP-A was found to bind to M. tuberculosis in a time- and [Ca2+]-dependent manner with a Kd of 1.9 x 10(-9) M and an apparent number of 6.3 x 10(2) SP-A binding sites/organism. Further, deglycosylated SP-A had minimal binding to M. tuberculosis, indicating that sugar moieties are important in this interaction. SP-A specifically binds to a 60-kD cell-wall protein from M. tuberculosis. SP-A-mediated attachment of 51Cr-labeled M. tuberculosis organisms to AMs is dependent on time, SP-A concentration, and Ca2+. M. tuberculosis attachment to murine AMs in the absence of SP-A was 12.8 +/- 0.9%; however, in the presence of 5 microg/ml SP-A the attachment increased to 38.6 +/- 2.9% (P < 0.001). SP-A-mediated attachment was significantly decreased from 38.6 +/- 2.9% to 18.7 +/- 3.3% (P < 0.05) in the presence of antihuman SP-A antibodies. When the attachment assay was repeated in the presence of alpha-methylene-D-mannosepyranosidase (mannosyl-BSA) and type V collagen, SP-A-mediated attachment decreased from 38.6 +/- 2.9% to 16.6 +/- 1.5% (P < 0.001) and 19.1 +/- 1.4% (P < 0.05), respectively. Further, deglycosylated SP-A had only a minimal effect on M. tuberculosis attachment to AMs. These data indicate that SP-A can mediate M. tuberculosis attachment to AMs, and suggest possible underlying mechanisms for this.
Am J Respir Cell Mol Biol 1997 Aug
PMID:Surfactant protein A (SP-A) mediates attachment of Mycobacterium tuberculosis to murine alveolar macrophages. 927 9


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