A5083680583- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Computational Drug Discovery Methods
- Biosensors and Analytical Detection
- Genomics and Phylogenetic Studies
- Synthesis and Biological Evaluation
- Cytomegalovirus and herpesvirus research
- Legionella and Acanthamoeba research
- Synthesis and biological activity
- Advanced biosensing and bioanalysis techniques
- Listeria monocytogenes in Food Safety
- Identification and Quantification in Food
- Microbial Metabolism and Applications
- Modular Robots and Swarm Intelligence
- RNA modifications and cancer
- Soft Robotics and Applications
- Cancer therapeutics and mechanisms
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Synthesis and Catalytic Reactions
- Adhesion, Friction, and Surface Interactions
- Diagnosis and treatment of tuberculosis
Broad Institute
2013-2019
Hamilton Thorne (United States)
2005-2010
A key to the pathogenic success of Mycobacterium tuberculosis (Mtb), causative agent tuberculosis, is capacity survive within host macrophages. Although several factors required for this survival have been identified, a comprehensive knowledge such and how they work together manipulate environment benefit bacterial are not well understood. To systematically identify Mtb intracellular growth, we screened an arrayed, non-redundant transposon mutant library by high-content imaging characterize...
The phylogenetic interrelationships of members the genus Listeria were investigated by using reverse transcriptase sequencing 16S rRNA. sequence data indicate that at intrageneric level consists following two closely related but distinct lines descent: (i) monocytogenes group species (including innocua, ivanovii, seeligeri, and welshimeri) (ii) grayi murrayi. At intergeneric a specific relationship between genera Brochothrix was evident. clearly demonstrated is phylogenetically remote from...
During Mycobacterium tuberculosis infection, a population of bacteria is thought to exist in nonreplicating state, refractory antibiotics, which may contribute the need for prolonged antibiotic therapy. The identification inhibitors state provides tools that can be used probe this hypothesis and physiology state. development such also has potential shorten duration therapy required. Here we describe novel assay amenable high-throughput chemical screening coupled with secondary assays use...
In an era of increasing resistance, new and effective strategies are needed for antibiotic discovery. Whole-cell active screens yield candidate compounds lacking mechanism-of-action (MOA) information thus do not provide biological insight prioritization. We previously reported PROSPECT ( PR imary screening O f S trains to P rioritize E xpanded C hemistry T argets), antimicrobial discovery strategy that measures chemical-genetic interactions between small molecules a pool Mycobacterium...
The nucleotide sequence of 1.5 Mb genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. genome to ∼66% completion. sequences, derived 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 rRNAs, and 15 tRNAs. gene density one per 1.4 kb is slightly lower than that Mycoplasma (1.2 kb). Of protein coding 44% have significant matches genes with well-defined functions....
Previous work established a coumarin scaffold as starting point for inhibition of Mycobacterium tuberculosis (Mtb) FadD32 enzymatic activity. After further profiling the inhibitor 4 revealed chemical instability, we discovered that quinoline ring circumvented this instability and had advantage offering additional substitution vectors to optimize. Ensuing SAR studies gave rise quinoline-2-carboxamides with potent anti-tubercular Further optimization ADME/PK properties culminated in 21b...
Amplification of single-stranded DNA circles has wide utility for a variety applications. The two-primer ramified rolling circle amplification (RAM) reaction provides exponential under isothermal conditions, creating regular laddered series double-stranded products. However, the molecular mechanism RAM remains unexplained. A model predicts accumulation product size series, and product-size ratios, that are consistent with observed involves generation increasing intermediate templates; those...
We describe a modified rRNA sequence analysis method which we used to determine the phylogenetic relationships among 58 species belonging genus Mycobacterium. combined sensitivity of reverse transcriptase PCR for amplifying nanogram amounts template material with elevated extension temperatures thermostable DNA polymerase from Thermus thermophilus. A 70°C transcription step permitted improved read-through highly structured templates members Mycobacterium, have G+C contents 66 71 mol%. The...
We report on a rapid, sensitive, Q-Beta replicase-amplified nucleic acid hybridization assay for the detection of Mycobacterium tuberculosis directly from spiked human sputum. Specimens were processed by either an N-acetyl-L-cysteine-NaOH or 2% NaOH digestion-decontamination method and then washed to neutralize pH cell pellet. The sputum pellets heated at 100 degrees C inactivate M. organisms. heat-inactivated samples mechanically lysed 5,000 rpm 6 min in GENE-TRAK Sample Processing...