A5113520618- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Antibiotic Resistance in Bacteria
- Virus-based gene therapy research
- Clostridium difficile and Clostridium perfringens research
- Viral gastroenteritis research and epidemiology
- Bacteriophages and microbial interactions
- Infectious Diseases and Tuberculosis
- Viral Infections and Outbreaks Research
- Hepatitis B Virus Studies
- Diagnosis and treatment of tuberculosis
- Bacterial Genetics and Biotechnology
- Viral Infections and Vectors
- Biochemical and Molecular Research
- Poxvirus research and outbreaks
- Appendicitis Diagnosis and Management
- Immune Response and Inflammation
- interferon and immune responses
- Immune Cell Function and Interaction
- Vitamin K Research Studies
- Microbial Natural Products and Biosynthesis
- Vanadium and Halogenation Chemistry
- Vibrio bacteria research studies
- SARS-CoV-2 and COVID-19 Research
- Toxoplasma gondii Research Studies
Icahn School of Medicine at Mount Sinai
2010-2024
Georgia State University
2018-2022
Albert Einstein College of Medicine
2007-2019
Maharaja Sayajirao University of Baroda
2018
Biocom
2018
Virginia Tech
2018
Louisiana State University
2018
Montefiore Medical Center
2000-2017
Howard Hughes Medical Institute
2014-2016
University of Pennsylvania
2005
The authors have developed a simple and highly efficient system for generating allelic exchanges in both fast- slow-growing mycobacteria. In this procedure gene of interest, disrupted by selectable marker, is cloned into conditionally replicating (temperature-sensitive) shuttle phasmid to generate specialized transducing mycobacteriophage. temperature-sensitive mutations the mycobacteriophage genome permit replication at permissive temperature 30 °C but prevent non-permissive 37 °C....
The granulomatous reaction is the hallmark of host response to infection with Mycobacterium tuberculosis. Despite its apparent importance defence against tubercle bacillus, remains be completely defined. present study used histological, immunohistochemical and flow-cytometric analyses characterize pulmonic tissues tuberculous mice humans. kinetics recruitment neutrophils, macrophages, dendritic cells, T B lymphocytes into lungs infected aerogenically virulent Erdman strain M. tuberculosis...
Significance Mycobacterium tuberculosis (Mtb) uses type VII secretion systems to secrete cognate protein pairs that alter host interactions. Here, we address the contributions of ESX-3 system Mtb growth and pathogenesis through a combination genetics, proteomics, studies both in vitro vivo. is demonstrated play critical role iron acquisition pair pf proteins belonging PE–PPE family (PE5–PPE4). In vivo, importance PE5–PPE4 was found depend upon genotype, likely reflecting capacity restrict...
ABSTRACT Specialized transduction has proven to be useful for generating deletion mutants in most mycobacteria, including virulent Mycobacterium tuberculosis . We have improved this system by developing (i) a single-step strategy the construction of allelic exchange substrates (AES), (ii) temperature-sensitive shuttle phasmid with greater cloning capacity than phAE87, and (iii) bacteriophage-mediated transient expression site-specific recombinase precisely excise antibiotic markers. The...
ABSTRACT Approximately one-third of the human population is latently infected with Mycobacterium tuberculosis , comprising a critical reservoir for disease reactivation. Despite importance latency in maintaining M. population, little known about mycobacterial factors that regulate persistence and Previous vitro studies have implicated family five related proteins, called resuscitation promoting (Rpfs), regulating growth. We studied vivo role rpf genes an established mouse model After aerosol...
Resuscitation-promoting factors (Rpfs), apparent peptidoglycan hydrolases, have been implicated in the reactivation of dormant bacteria. We previously demonstrated that deletion rpfB impaired Mycobacterium tuberculosis a mouse model. Because M. encodes five Rpf paralogues, redundant functions among family members might obscure rpf single-knockout phenotypes. A series double knockouts were therefore generated. One mutant, DeltarpfAB, exhibited several striking Consistent with proposed cell...
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...
Abstract A major constraint for developing new anti-tuberculosis drugs is the limited number of validated targets that allow eradication persistent infections. Here, we uncover a vulnerable component Mycobacterium tuberculosis (Mtb) persistence metabolism, aspartate pathway. Rapid death threonine and homoserine auxotrophs points to distinct susceptibility Mtb inhibition this Combinatorial metabolomic transcriptomic analysis reveals inability produce leads deregulation kinase, causing flux...
Mycobacterium tuberculosis possesses five genes with significant homology to the resuscitation-promoting factor (Rpf) of Micrococcus luteus. The M. luteus Rpf is a secreted approximately 16-kDa protein which restores active growth cultures rendered dormant by prolonged incubation in stationary phase. More recently, Rpf-like proteins have been shown stimulate extended-stationary-phase bovis BCG. These data suggest that can influence mycobacteria; however, studies do not demonstrate specific...
ABSTRACT Drug resistance in Mycobacterium tuberculosis has become a serious global health threat, which is now complicated by the emergence of extensively drug-resistant strains. New drugs that are active against (TB) needed. We chose to search for new inhibitors enoyl-acyl carrier protein (ACP) reductase InhA, target first-line TB drug isoniazid (also known as isonicotinoic acid hydrazide [INH]). A subset chemical library, composed 300 compounds inhibiting Plasmodium falciparum enoyl...
We have previously shown that the Mycobacterium tuberculosis universal stress protein Rv2623 regulates mycobacterial growth and may be required for establishment of tuberculous persistence. Here, yeast two-hybrid affinity chromatography experiments demonstrated interacts with one two forkhead-associated domains (FHA I) Rv1747, a putative ATP-binding cassette transporter annotated to export lipooligosaccharides. FHA are signaling modules mediate protein-protein interactions modulate wide...
Mycobacterium tuberculosis (Mtb) possesses five type VII secretion systems (T7SS), virulence determinants that include the apparatus and associated substrates. Mtb strains deleted for genes encoding substrates of ESX-3 T7SS, esxG or esxH, require iron supplementation in vitro growth are highly attenuated vivo. In a subset infected mice, suppressor mutants esxH deletions were isolated, which enabled to high titers restored virulence. Suppression was conferred by mechanisms cause...
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 G enetic engineering has contributed greatly to our understanding of Mycobacterium tuberculosis biology and facilitated antimycobacterial vaccine development. However, methods generate M. deletion mutants remain labor-intensive relatively inefficient. Here, are described that significantly enhance the efficiency (greater than 100-fold) recovering by expression mycobacteriophage recombineering functions during course infection with specialized transducing phages delivering allelic...
The 14.7-kilodalton protein (14.7K protein) encoded by the adenovirus (Ad) E3 region inhibits tumor necrosis factor alpha (TNF-alpha)-mediated lysis of cells in tissue culture experiments, but relevance this effect vivo is incompletely understood. To examine ability Ad 14.7K to block TNF upon viral pathogenesis a murine model, we cloned protein-encoding gene into vaccinia virus (VV), permitting its study isolation from other immunomodulatory proteins. for TNF-alpha was inserted same VV...
Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet mechanisms that regulate these processes remain unclear.The Mycobacterium tuberculosis universal stress protein (USP) homolog, rv2623, is among most highly induced genes when tubercle bacillus subjected to hypoxia nitrosative stress, conditions thought promote latency.Induction rv2623 also occurs M. encounters associated with growth arrest, such as intracellular milieu macrophages lungs mice...
The adenovirus (Ad) 14.7-kDa protein, which is called "14.7K," has been shown to function as a general inhibitor of tumor necrosis factor alpha (TNF) cytolysis in tissue culture assays, and the effect this antagonism on viral pathogenesis vivo recently explored. In infections immunocompetent BALB/c mice, we have previously that Ad type 2 (Ad2) 14.7K, when cloned into vaccinia virus (VV) vector combination with gene for murine TNF, able counteract much attenuating TNF VV virulence. present...
Human adenoviruses (Ad) contain a complex transcription region (E3) which codes for proteins that interact with several arms of the immune system. However, E3 genes are not essential replication in tissue culture. An E3-encoded 19,000-molecular-weight (19K) glycoprotein (gp19K) binds to class I major histocompatibility (MHC) endoplasmic reticulum and prevents MHC transport cell surface. Three other involved inhibition apoptosis by tumor necrosis factor alpha. The entire genomic DNA was...