A5070828411- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Biochemical and Molecular Research
- Bacteriophages and microbial interactions
- Metabolomics and Mass Spectrometry Studies
- Antibiotic Resistance in Bacteria
- Pneumocystis jirovecii pneumonia detection and treatment
- ATP Synthase and ATPases Research
- Cancer therapeutics and mechanisms
- Bacterial Genetics and Biotechnology
- Neurological diseases and metabolism
- Vitamin C and Antioxidants Research
- Diet, Metabolism, and Disease
- Gut microbiota and health
- Multiple Myeloma Research and Treatments
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Marketing and Advertising Strategies
- Transportation and Mobility Innovations
- Infectious Diseases and Mycology
- Advanced Proteomics Techniques and Applications
- Platelet Disorders and Treatments
- Microbial Metabolic Engineering and Bioproduction
- Ocular Infections and Treatments
- Clostridium difficile and Clostridium perfringens research
Weill Cornell Medicine
2019-2025
Cornell University
2003-2025
Center for Global Health
2020
New York Proton Center
2017
Albert Einstein College of Medicine
2007-2017
United States Department of the Navy
2017
Howard Hughes Medical Institute
2013-2016
The Bronx Defenders
2014
Excessive consumption of beverages sweetened with high-fructose corn syrup (HFCS) is associated obesity and an increased risk colorectal cancer. Whether HFCS contributes directly to tumorigenesis unclear. We investigated the effects daily oral administration in adenomatous polyposis coli (APC) mutant mice, which are predisposed develop intestinal tumors. The HFCS-treated mice showed a substantial increase tumor size grade absence metabolic syndrome. concentrations fructose glucose lumen...
Significance Tuberculosis (TB) patients would greatly benefit from shorter treatment options. The of drug-susceptible TB, a disease caused by the bacillus Mycobacterium tuberculosis , is lengthy and strenuous process. This long therapy because ability small population cells to become drug-tolerant. Here, we demonstrate that addition thiols drug-treated M. prevents emergence drug-tolerant but also drug-resistant leading sterilization cultures in vitro. potentiate drug activity preventing...
In chronic infection, Mycobacterium tuberculosis bacilli are thought to enter a metabolic program that provides sufficient energy for maintenance of the protonmotive force, but is insufficient meet demands cellular growth. We sought understand this downshift genetically by targeting succinate dehydrogenase, enzyme which couples growth processes controlled TCA cycle with production resulting from electron transport chain. M. contains two operons predicted encode dehydrogenase enzymes (sdh-1...
A potent, noncytotoxic indazole sulfonamide was identified by high-throughput screening of >100,000 synthetic compounds for activity against Mycobacterium tuberculosis (Mtb). This compound did not directly inhibit cell wall biogenesis but triggered a slow lysis Mtb cells as measured release intracellular green fluorescent protein (GFP). Isolation resistant mutants followed whole-genome sequencing showed an unusual gene amplification 40 region spanning from Rv3371 to Rv3411c and in one case...
ABSTRACT Succinate:quinone oxidoreductase (Sdh) is a membrane-bound complex that couples the oxidation of succinate to fumarate in cytoplasm reduction quinone quinol membrane. Mycobacterial species harbor genes for two putative sdh operons, but individual roles these operons are unknown. In this communication, we show Mycobacterium smegmatis mc 2 155 expresses dehydrogenases designated Sdh1 and Sdh2. encoded by five-gene operon (MSMEG_0416-MSMEG_0420), Sdh2 four-gene (MSMEG_1672-MSMEG_1669)....
The new medicinal compound bedaquiline (BDQ) kills Mycobacterium tuberculosis by inhibiting F1Fo-ATP synthase. BDQ is bacteriostatic for 4 to 7 days and relatively slowly compared other frontline (TB) drugs. Here we show that killing with can be improved significantly cytochrome bd oxidase, a non-proton-pumping terminal oxidase. was instantly bactericidal against oxidase null mutant of M. tuberculosis, the rate increased more than 50%. We propose this exclusively bacterial enzyme should...
Mycobacterium tuberculosis bacilli display two signature features: acid-fast staining and the capacity to induce long-term latent infections in humans. However, mechanisms governing these important processes remain largely unknown. Ser/Thr phosphorylation has recently emerged as an regulatory mechanism allowing mycobacteria adapt their cell wall structure/composition response environment. Herein, we evaluated whether of KasB, a crucial mycolic acid biosynthetic enzyme, could modulate...
A wrench in the gears of life Tuberculosis is a global health crisis that threatens to become worse as resistance existing drugs emerges. Identifying ideal targets for drug development requires knowledge weak points biochemical pathways are specific pathogen but absent hosts. Ballinger et al. identified small molecule inhibits enzyme phosphopantetheinyl transferase (PptT), which crucial biosynthesis mycobacterial structural and virulence lipids (see Perspective by Mizrahi Warner). Treatment...
The ability of Mycobacterium tuberculosis (Mtb) to resist and tolerate antibiotics complicates the development improved (TB) chemotherapies. Here we define Mtb protein CinA as a major determinant drug tolerance potential target shorten TB chemotherapy. By reducing fraction drug-tolerant persisters, genetic inactivation cinA accelerated killing by four in clinical use: isoniazid, ethionamide, delamanid pretomanid. ΔcinA was killed rapidly conditions known impede efficacy such during nutrient...
The difficulty of diagnosing active tuberculosis (TB) and lack rapid drug susceptibility testing (DST) at the point care remain critical obstacles to TB control. This report describes a high-intensity mycobacterium-specific-fluorophage (φ(2)GFP10) that for first time allows direct visualization Mycobacterium in clinical sputum samples. Engineered features distinguishing φ(2)GFP10 from previous reporter phages include an improved vector backbone with increased cloning capacity superior...
Abstract Mycobacterium tuberculosis (Mtb), a leading cause of death from infection, completes its life cycle entirely in humans except for transmission through the air. To begin to understand how Mtb survives aerosolization, we mimicked liquid and atmospheric conditions experienced by before after exhalation using model aerosol fluid (MAF) based on water-soluble, lipidic cellular constituents necrotic lesions. MAF induced drug tolerance Mtb, remodeled transcriptome protected dying...
Mycobacterium tuberculosis (Mtb), a leading cause of death from infection, completes its life cycle entirely in humans except for transmission through the air. To begin to understand how Mtb survives aerosolization, we mimicked liquid and atmospheric conditions experienced by before after exhalation using model aerosol fluid (MAF) based on water-soluble, lipidic, cellular constituents necrotic lesions. MAF induced drug tolerance Mtb, remodeled transcriptome, protected dying microdroplets...
Mycobacterium tuberculosis (Mtb) displays a high degree of metabolic plasticity to adapt challenging host environments. Genetic evidence suggests that Mtb relies mainly on fatty acid catabolism in the host. However, also maintains functional glycolytic pathway and its role cellular metabolism has yet be understood. Pyruvate kinase catalyzes last rate-limiting step glycolysis genome harbors one putative pyruvate (pykA, Rv1617). Here we show pykA encodes an active is allosterically activated...
Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose glucose-6-phosphate. In order to assess drug potential phosphatase, we generated a conditional mutant M. tuberculosis allowing regulated gene silencing otsB2....
ABSTRACT Mycobacterium haemophilum is an emerging pathogen associated with a variety of clinical syndromes, most commonly skin infections in immunocompromised individuals. M. exhibits unique requirement for iron supplementation to support its growth culture, but the basis this property and how it may shape pathogenesis unclear. Using combination Illumina, PacBio, Sanger sequencing, complete genome sequence was determined. Guided by sequence, experiments were performed define requirements ....
ABSTRACT Nicotinamide adenine dinucleotide (NAD) and its phosphorylated derivative (NADP) are essential cofactors that participate in hundreds of biochemical reactions have emerged as therapeutic targets cancer, metabolic disorders, neurodegenerative diseases, infections, including tuberculosis. The biological basis for the essentiality NAD(P) most settings, however, remains experimentally unexplained. Here, we report inactivation terminal enzyme NAD synthesis, synthetase (NadE), elicits...
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