A5068460948- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Antibiotic Resistance in Bacteria
- Plant-Microbe Interactions and Immunity
- Plant Pathogenic Bacteria Studies
- Biochemical and Molecular Research
- Diagnosis and treatment of tuberculosis
- Cancer therapeutics and mechanisms
- Bacterial Genetics and Biotechnology
- Legume Nitrogen Fixing Symbiosis
- RNA and protein synthesis mechanisms
- Enzyme function and inhibition
- Phenothiazines and Benzothiazines Synthesis and Activities
- Plant Virus Research Studies
- Escherichia coli research studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Bacterial biofilms and quorum sensing
- Gut microbiota and health
- Clostridium difficile and Clostridium perfringens research
- Pneumonia and Respiratory Infections
- Microbial infections and disease research
- Genomics and Phylogenetic Studies
- Microbial Community Ecology and Physiology
- Planarian Biology and Electrostimulation
- Adenosine and Purinergic Signaling
Michigan State University
2016-2025
Pediatrics and Genetics
2025
Kazakhstan Medical University
2021
GTx (United States)
2020
Michigan United
2017
Cornell University
2004-2015
New York State College of Veterinary Medicine
2013
Ithaca College
2005-2007
Rockefeller University
2005
United States Department of Agriculture
2002
The Pseudomonas syringae protein AvrPtoB is translocated into plant cells, where it inhibits immunity-associated programmed cell death (PCD). structure of a C-terminal domain that essential for anti-PCD activity reveals an unexpected homology to the U-box and RING-finger components eukaryotic E3 ubiquitin ligases, we show has ligase activity. Mutation conserved residues involved in binding E2 ubiquitin–conjugating enzymes abolishes this vitro, as well tomato leaves, which dramatically...
Mycobacterium tuberculosis (Mtb) relies on a specialized set of metabolic pathways to support growth in macrophages. By conducting an extensive, unbiased chemical screen identify small molecules that inhibit Mtb metabolism within macrophages, we identified significant number novel compounds limit macrophages and medium containing cholesterol as the principle carbon source. Based this observation, developed chemical-rescue strategy target enzymes involved metabolism. This approach two HsaAB...
Successful chemotherapy against Mycobacterium tuberculosis (Mtb) must eradicate the bacterium within context of its host cell. However, our understanding impact this environment on antimycobacterial drug action remains incomplete. Intriguingly, we find that Mtb in myeloid cells isolated from lungs experimentally infected mice exhibit tolerance to both isoniazid and rifampin a degree proportional activation status cells. These data are confirmed by vitro infections resting versus activated...
The ability of Pseudomonas syringae pv. tomato DC3000 to parasitize and Arabidopsis thaliana depends on genes activated by the HrpL alternative sigma factor. To support various functional genomic analyses DC3000, specifically, identify involved in pathogenesis, we developed a draft sequence used an iterative process involving computational gene expression techniques virulence-implicated downstream HrpL-responsive promoters. Hypersensitive response pathogenicity (Hrp) promoters are known...
Microbial pathogens of both plants and animals employ virulence factors that suppress the host immune response. The tomato pathogen Pseudomonas syringae injects AvrPtoB type III effector protein into plant cell to programmed death (PCD) associated with immunity. also inhibits PCD in yeast, indicating manipulates a conserved component eukaryotic PCD. To identify targets AvrPtoB, we performed yeast two-hybrid screen identified ubiquitin (Ub) as strong interactor. is ubiquitinated vitro...
Following phagocytosis by macrophages, Mycobacterium tuberculosis (Mtb) senses the intracellular environment and remodels its gene expression for growth in phagosome. We have identified an acid phagosome regulated (aprABC) locus that is unique to Mtb complex whose induced during acidic environments vitro macrophages. Using aprA promoter, we generated a strain exhibits high levels of inducible fluorescence response medium aprABC dependent on two-component regulator phoPR, linking phoPR...
The ability of Mycobacterium tuberculosis (Mtb) to thrive in its phagosomal niche is critical for establishment a chronic infection. This requires that Mtb senses and responds intraphagosomal signals such as pH. We hypothesized would respond additional factors correlate with maturation. Here, we demonstrate [Cl⁻] pH inversely phagosome maturation, identify Cl⁻ novel environmental cue Mtb. synergistically, part through the activity two-component regulator phoPR. Following identification...
Summary During pathogenesis, M ycobacterium tuberculosis ( Mtb ) colonizes environments, such as the macrophage or necrotic granuloma, that are acidic and rich in cholesterol fatty acids. The goal of this study was to examine how pH available carbon sources interact regulate physiology. Here we report growth at requires host‐associated function intersection glycolysis TCA cycle, pyruvate, acetate, oxaloacetate cholesterol. In contrast, other tested sources, fully arrests its establishes a...
ABSTRACT Mycobacterium tuberculosis must sense and adapt to host environmental cues establish maintain an infection. The two-component regulatory system PhoPR plays a central role in sensing responding acidic pH within the macrophage is required for M. intracellular replication growth vivo . Therefore, isolation of compounds that inhibit PhoPR-dependent adaptation may identify new antivirulence therapies treat tuberculosis. Here, we report carbonic anhydrase inhibitor ethoxzolamide inhibits...
Mycobacterium tuberculosis (Mtb) senses and adapts to acidic environments during the course of infection. Acidic pH-dependent adaptations include induction metabolic genes associated with anaplerosis growth arrest on specific carbon sources. Here we report that deletion isocitrate lyase or phosphoenolpyruvate carboxykinase results in reduced at pH altered metabolite profiles, supporting remodeling anaplerotic metabolism is required for adaptation. Mtb cultured 5.7 minimal medium containing...
Emergence of drug-resistant and multidrug-resistant Mycobacterium tuberculosis (Mtb) strains is a major barrier to (TB) eradication, as it leads longer treatment regimens in many cases failure. Thus, there an urgent need explore new TB drugs combinations, order shorten improve outcomes. Here, we evaluated the potential two Asian African traditional medicinal plants, Artemisia annua, natural source artemisinin (AN), afra, sources novel antitubercular agents. Our goal was measure activity A....
Summary Resistance to bacterial speck disease in tomato is activated by the physical interaction of host Pto kinase with either sequence‐dissimilar type III effector proteins AvrPto or AvrPtoB (HopAB2) from Pseudomonas syringae pv. . Pto‐mediated immunity requires Prf, a protein nucleotide‐binding site and leucine‐rich repeats. The N‐terminal 307 amino acids were previously reported interact kinase, we show here that this region (AvrPtoB 1‐307 ) sufficient for eliciting Pto/Prf‐dependent...
Mycobacterium tuberculosis (Mtb) possesses a two-component regulatory system, DosRST, that enables Mtb to sense host immune cues and establish state of nonreplicating persistence (NRP). NRP bacteria are tolerant several antimycobacterial drugs in vitro thought play role the long course therapy. Previously, we reported discovery six novel chemical inhibitors named HC101A–106A, from whole cell, reporter-based phenotypic high throughput screen. Here, report functional mechanism action studies...
A search for alternative Mycobacterium abscessus treatments led to our interest in the two-component regulator DosRS, which, tuberculosis , is required bacterium establish a state of nonreplicating, drug-tolerant persistence response variety host stresses. We show here that genetic disruption dosRS impairs adaptation M. hypoxia, resulting decreased bacterial survival after oxygen depletion, reduced tolerance number antibiotics vitro and vivo, inhibition biofilm formation. determined three...
Significance Mycobacteria use ESX systems to transport protein substrates across the cytoplasmic membrane. The ESX-1 system is required for mycobacterial pathogenesis in Mycobacterium tuberculosis ( M. tb ), cause of (TB). Differences expression genes encoding directly impacts transmission and virulence. Deletion exporters results reduced levels mycobacteria. Here, we define a fundamental mechanism regulation marinum , pathogenic species model . We demonstrate that transcriptional linked...