33 results for "Smith, Issar"
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Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence
Tuberculosis (TB), one of the oldest known human diseases. is still is one of the major causes of mortality, since two million people die each year from this malady. TB has many manifestations, affecting bone, the central nervous system, and many other organ systems, but it is primarily a pulmonary…
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Location of the SPO2 Attachment Site and the Bryamycin Resistance Marker on the Bacillus subtilis Chromosome
The attachment site on the Bacillus subtilis chromosome for the lysogenic bacteriophage SPO2 has been mapped by PBS1-mediated transduction and was found to be between spc-2 and lin-2, showing 90% linkage to the former and 30% linkage to the latter marker. In the course of these studies the bry-2…
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Identification of an ABC Transporter Required for Iron Acquisition and Virulence in Mycobacterium tuberculosis
Iron availability affects the course of tuberculosis infection, and the ability to acquire this metal is known to be essential for replication of Mycobacterium tuberculosis in human macrophages. M. tuberculosis overcomes iron deficiency by producing siderophores. The relevance of siderophore…
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Progress and New Directions in Genetics of Tuberculosis
Tuberculosis (TB), along with AIDS and malaria, is one of the three major killers among infectious diseases. New approaches to preventing, diagnosing, and curing TB are needed, which depend on a better understanding of Mycobacterium tuberculosis and the host. The National Heart, Lung, and Blood…
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Structure of the DNA-binding domain of the response regulator PhoP from Mycobacterium tuberculosis
The PhoP-PhoR two-component signaling system from Mycobacterium tuberculosis is essential for the virulence of the tubercle bacillus. The response regulator, PhoP, regulates expression of over 110 genes. In order to elucidate the regulatory mechanism of PhoP, we determined the crystal structure of…
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Responses of Mycobacterium tuberculosis to Growth in the Mouse Lung
Using a promoter trap, we have identified 56 Mycobacterium tuberculosis genes preferentially expressed in the mouse lung. Quantitative real-time PCR showed that RNA levels of several genes were higher from bacteria growing in mouse lungs than from broth cultures. These results support the current…
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Rv1106c from Mycobacterium tuberculosis is a 3β-hydroxysteroid dehydrogenase
New approaches are required to combat M. tuberculosis (Mtb), especially the multi and extremely drug resistant and organisms (MDR-TB and XDR-TB). There are many reports that mycobacteria oxidize 3β-hydroxysterols to 3-ketosteroids, but the enzyme(s) responsible for this activity have not been…
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Protein Dynamics in Iron-Starved Mycobacterium Tuberculosis Revealed by Turnover and Abundance Measurement Using Hybrid-Linear Ion Trap-Fourier Transform Mass Spectrometry
To study the proteome response of Mycobacterium tuberculosis H37Rv to a change in iron level, iron-starved late-log-phase cells were diluted in fresh low- and high-iron media containing [(15)N] labeled asparagine as the sole nitrogen source for labeling the proteins synthesized upon dilution. We…
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The Mycobacterium tuberculosis High-Affinity Iron Importer, IrtA, Contains an FAD-Binding Domain
Iron is an essential nutrient not freely available to microorganisms infecting mammals. To overcome iron deficiency, bacteria have evolved various strategies including the synthesis and secretion of high-affinity iron chelators known as siderophores. The siderophores produced and secreted by…
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Immunogenicity and Protection Induced by a Mycobacterium tuberculosis sigE Mutant in a BALB/c Mouse Model of Progressive Pulmonary Tuberculosis
Tuberculosis is still one of the main challenges to human global health, leading to about two million deaths every year. One of the reasons for its success is the lack of efficacy of the widely used vaccine Mycobacterium bovis BCG. In this article, we analyze the potential use of an attenuated…
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Global Transcriptional Profile of Mycobacterium tuberculosis during THP-1 Human Macrophage Infection
During lung infection, Mycobacterium tuberculosis resides in macrophages and subverts the bactericidal mechanisms of these professional phagocytes. Comprehension of this host-pathogen relationship is fundamental for the development of new therapies to cure and prevent tuberculosis. In this work, we…
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Cholesterol Is Not an Essential Source of Nutrition for Mycobacterium tuberculosis during Infection
Rv1106c (hsd; 3β-hydroxysteroid dehydrogenase) is required by Mycobacterium tuberculosis for growth on cholesterol as a sole carbon source, whereas Rv3409c is not. Mutation of Rv1106c does not reduce Mycobacterium tuberculosis growth in infected macrophages or guinea pigs. We conclude that…
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Differential gene expression between Mycobacterium bovis and Mycobacterium tuberculosis
The high sequence identity among the Mycobacterium bovis and Mycobacterium tuberculosis genomes contrasts with the physiological differences reported between these pathogens, suggesting that variations in gene expression may be involved. In this study, microarray hybridization was used to compare…
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Analysis of tnrA Alleles Which Result in a Glucose-Resistant Sporulation Phenotype in Bacillus subtilis
Bacillus subtilis cells cannot sporulate in the presence of catabolites such as glucose. During the analysis of Tn10-generated mutants, we found that deletion of the C-terminal region of the tnrA gene, which encodes a global regulator that positively regulates a number of genes in response to…
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Mycobacterium tuberculosis Genes Induced during Infection of Human Macrophages†
We identified Mycobacterium tuberculosis genes preferentially expressed during infection of human macrophages using a promoter trap adapted for this pathogen. inhA encodes an enoyl-acyl carrier protein reductase that is required for mycolic acid biosynthesis (A. Quemard et al., Biochemistry…
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Binding of Thiostrepton to Ribosomes from Thiostrepton-Sensitive and -Resistant Bacillus subtilis Strains
Binding of [(35)S]thiostrepton to ribosomes from thiostrepton-sensitive and -resistant strains of Bacillus subtilis was studied. Ribosomes from thiostrepton-resistant strains bound relatively little thiostrepton compared with ribosomes from thiostrepton-sensitive B. subtilis. In addition, ribosomes…
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σ Factors and Global Gene Regulation in Mycobacterium tuberculosis
Also available at: PubMed Central
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Cholesterol Metabolism Increases the Metabolic Pool of Propionate in M. tuberculosis
Mycobacterium tuberculosis can metabolize cholesterol to both acetate and propionate. The mass of isolated phthiocerol dimycoserate, a methyl-branched fatty acylated polyketide, was used as a reporter for intracellular propionate metabolic flux. When Mycobacterium tuberculosis is grown using…
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Real-time measurement of in vitro transcription
We have developed a simple method to measure RNA synthesis in real time. In this technique, transcription reactions are performed in the presence of molecular beacons that possess a 2′-O-methylribonucleotide backbone. These probes become fluorescent as they hybridize to nascent RNA during the…