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One or more keywords matched the following properties of Sassetti, Christopher
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Academic Background:

Ph.D. University of California, San Francisco, CA. 2000
Damon Runyon Foundation Scholar (www.damonrunyon.org)

Other:

Howard Hughes Medical Institute Investigator (www.hhmi.org)

Pathogenesis of tuberculosis

Christopher Sassetti, Ph.D.

Mycobacterium tuberculosis is often called the world's most successful pathogen. It is estimated that one third of the human population has been exposed to this organism, and tuberculosis (TB) kills millions every year. Unlike many other bacterial pathogens that cause acute disease and replicate only in a specific host niche, M. tuberculosis can maintain a chronic infection by adapting to many distinctly different host microenvironments. Our lab is focused on defining the survival strategies used by this pathogen in each of these environments.

To this end, we have developed a variety of new methodologies, which take advantage of both classical genetic tools and genome sequence information. Using these methods, we have identified hundreds of mycobacterial genes that are specifically required for the bacterium to survive under a variety of conditions including acute and chronic infection models. Current work is focused on the characterizing the functional roles played by these virulence systems.

Specific projects include:

1)Understanding how nutrients are acquired in vivo. M. tuberculosis resides largely within a membrane bound compartment during infection, and it remains unclear how the bacterium acquires nutrients in this apparently isolated niche. We have identified a series of lipid and carbohydrate import systems that are critical for growth during specific phases of disease. One of these functions as a sterol uptake system, which has lead to the discovery that host cholesterol is an essential carbon source during chronic infection (see figure). We are currently focused on defining the mechanisms by which the bacterium extracts and degrades nutrients, such as cholesterol, from the host cell and understanding why the nutritional habits of the bacterium change so dramatically as disease progresses.

Cholesterol

RFP-labeledM. tuberculosis resides in
cholesterol rich regions of the cell (green).

2)Understanding the unique physiology of the mycobacterial cell wall. The cell envelope of M. tuberculosis forms a unique barrier to environmental insults and is essential for the viability of the pathogen. Using a combination of high-throughput genetic, biochemical and structural approaches, we are investigating how phosphosignaling cascades regulate the synthesis of this complex structure.

Cell Wall Systhesis

Cell wall synthesis (green) is dysregulated in mycobacterial mutants compared to wild type cells (red).

3)Metabolic regulation of cell growth and antibiotic sensitivity. The immune system of the host exerts a variety of stresses on the bacterium, which cause it to stop replicating and become refractory to antibiotic treatment. Using a combination of genetic and metabolomic approaches, we are defining the mechanisms by which M. tuberculosis senses these stresses and responds by reducing its growth and metabolic rate.

To see information on the Sassetti Lab .

For more information, visit hisHoward Hughes Medical Institute web page.

One or more keywords matched the following items that are connected to Sassetti, Christopher
Item TypeName
Academic Article Comprehensive identification of conditionally essential genes in mycobacteria.
Academic Article A new site-specific integration system for mycobacteria.
Academic Article Characterization of mycobacterial virulence genes through genetic interaction mapping.
Academic Article Transposon site hybridization in Mycobacterium tuberculosis.
Academic Article Nitrile-inducible gene expression in mycobacteria.
Academic Article NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis.
Academic Article Variation among genome sequences of H37Rv strains of Mycobacterium tuberculosis from multiple laboratories.
Academic Article Relics of selection in the mycobacterial genome.
Academic Article Mycobacterium tuberculosis induces an atypical cell death mode to escape from infected macrophages.
Academic Article High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism.
Academic Article Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1?.
Academic Article Bayesian analysis of gene essentiality based on sequencing of transposon insertion libraries.
Academic Article Infection control in cystic fibrosis: share and share alike.
Academic Article Genes required for mycobacterial growth defined by high density mutagenesis.
Academic Article Genetic requirements for mycobacterial survival during infection.
Academic Article The folate pathway is a target for resistance to the drug para-aminosalicylic acid (PAS) in mycobacteria.
Academic Article Mutually dependent secretion of proteins required for mycobacterial virulence.
Academic Article NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2.
Academic Article Mycobacterial persistence requires the utilization of host cholesterol.
Academic Article igr Genes and Mycobacterium tuberculosis cholesterol metabolism.
Academic Article Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide.
Academic Article Phthiocerol dimycocerosate transport is required for resisting interferon-gamma-independent immunity.
Academic Article Role of cholesterol in Mycobacterium tuberculosis infection.
Academic Article Inducible expression systems for mycobacteria.
Academic Article Metabolic regulation of mycobacterial growth and antibiotic sensitivity.
Academic Article A phosphorylated pseudokinase complex controls cell wall synthesis in mycobacteria.
Academic Article Cholesterol catabolism by Mycobacterium tuberculosis requires transcriptional and metabolic adaptations.
Academic Article Role in metal homeostasis of CtpD, a Co²? transporting P(1B4)-ATPase of Mycobacterium smegmatis.
Academic Article Cyclic AMP regulation of protein lysine acetylation in Mycobacterium tuberculosis.
Academic Article Global assessment of genomic regions required for growth in Mycobacterium tuberculosis.
Academic Article A novel P(1B)-type Mn2+-transporting ATPase is required for secreted protein metallation in mycobacteria.
Academic Article DNA methylation impacts gene expression and ensures hypoxic survival of Mycobacterium tuberculosis.
Concept Mycobacterium tuberculosis
Concept Mycobacterium Infections, Nontuberculous
Concept Nontuberculous Mycobacteria
Concept Mycobacterium
Concept Mycobacterium leprae
Concept Mycobacterium smegmatis
Concept Mycobacterium bovis
Academic Article Identification of new drug targets and resistance mechanisms in Mycobacterium tuberculosis.
Academic Article Differential roles for the Co(2+) /Ni(2+) transporting ATPases, CtpD and CtpJ, in Mycobacterium tuberculosis virulence.
Academic Article Immunology: Fixing the odds against tuberculosis.
Academic Article Subpolar addition of new cell wall is directed by DivIVA in mycobacteria.
Academic Article Biochemical and spatial coincidence in the provisional Ser/Thr protein kinase interaction network of Mycobacterium tuberculosis.
Academic Article New TB treatments hiding in plain sight.
Academic Article Identifying essential genes in Mycobacterium tuberculosis by global phenotypic profiling.
Academic Article New insights into TB physiology suggest untapped therapeutic opportunities.
Academic Article Mycobacterial recombineering.
Academic Article Label-free Quantitative Proteomics Reveals a Role for the Mycobacterium tuberculosis SecA2 Pathway in Exporting Solute Binding Proteins and Mce Transporters to the Cell Wall.
Academic Article The Oxidative Stress Network of Mycobacterium tuberculosis Reveals Coordination between Radical Detoxification Systems.
Academic Article Phosphorylation of the Peptidoglycan Synthase PonA1 Governs the Rate of Polar Elongation in Mycobacteria.
Academic Article Peptidoglycan synthesis in Mycobacterium tuberculosis is organized into networks with varying drug susceptibility.
Academic Article Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection.
Academic Article Spatially distinct and metabolically active membrane domain in mycobacteria.
Academic Article Fine-tuning of Substrate Affinity Leads to Alternative Roles of Mycobacterium tuberculosis Fe2+-ATPases.
Academic Article A cytoplasmic peptidoglycan amidase homologue controls mycobacterial cell wall synthesis.
Academic Article Tuberculosis Susceptibility and Vaccine Protection Are Independently Controlled by Host Genotype.
Academic Article Structural and Genetic Analyses of the Mycobacterium tuberculosis Protein Kinase B Sensor Domain Identify a Potential Ligand-binding Site.
Academic Article Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis.
Academic Article Programmable transcriptional repression in mycobacteria using an orthogonal CRISPR interference platform.
Academic Article Statistical analysis of genetic interactions in Tn-Seq data.
Academic Article Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis.
Academic Article A Lysine Acetyltransferase Contributes to the Metabolic Adaptation to Hypoxia in Mycobacterium tuberculosis.
Academic Article A Parallel Adder Coordinates Mycobacterial Cell-Cycle Progression and Cell-Size Homeostasis in the Context of Asymmetric Growth and Organization.
Academic Article Unravelling the pleiotropic role of the MceG ATPase in Mycobacterium smegmatis.
Academic Article Molecular and functional analysis of the mce4 operon in Mycobacterium smegmatis.
Academic Article Consequence of enhanced LC3-trafficking for a live, attenuated M. tuberculosis vaccine.
Academic Article Mycobacterium tuberculosis is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA.
Academic Article Tolerating the Unwelcome Guest; How the Host Withstands Persistent Mycobacterium tuberculosis.
Academic Article The Phagocyte Oxidase Controls Tolerance to Mycobacterium tuberculosis Infection.
Academic Article Modeling Diversity: Do Homogeneous Laboratory Strains Limit Discovery?
Academic Article Advancing Translational Science for Pulmonary Nontuberculous Mycobacterial Infections. A Road Map for Research.
Academic Article Role of Granulocyte-Macrophage Colony-Stimulating Factor Production by T Cells during Mycobacterium tuberculosis Infection.
Academic Article ORBIT: a New Paradigm for Genetic Engineering of Mycobacterial Chromosomes.
Academic Article Large-scale chemical-genetics yields new M. tuberculosis inhibitor classes.
Academic Article Common Variants in the Glycerol Kinase Gene Reduce Tuberculosis Drug Efficacy.
Academic Article Statistical analysis of variability in TnSeq data across conditions using zero-inflated negative binomial regression.
Academic Article Functionally Overlapping Variants Control Tuberculosis Susceptibility in Collaborative Cross Mice.
Academic Article The structure of the endogenous ESX-3 secretion system.
Academic Article Evaluation of IL-1 Blockade as an Adjunct to Linezolid Therapy for Tuberculosis in Mice and Macaques.
Academic Article Granulocytes act as a niche for Mycobacterium tuberculosis growth.
Academic Article CD11cHi monocyte-derived macrophages are a major cellular compartment infected by Mycobacterium tuberculosis.
Academic Article Distinct Bacterial Pathways Influence the Efficacy of Antibiotics against Mycobacterium tuberculosis.
Academic Article Cell-Cycle-Associated Expression Patterns Predict Gene Function in Mycobacteria.
Academic Article A natural polymorphism of Mycobacterium tuberculosis in the esxH gene disrupts immunodomination by the TB10.4-specific CD8 T cell response.
Academic Article M. tuberculosis Reprograms Hematopoietic Stem Cells to Limit Myelopoiesis and Impair Trained Immunity.
Academic Article Phosphorylation on PstP Regulates Cell Wall Metabolism and Antibiotic Tolerance in Mycobacterium smegmatis.
Academic Article Two-Way Regulation of MmpL3 Expression Identifies and Validates Inhibitors of MmpL3 Function in Mycobacterium tuberculosis.
Academic Article Sirtuin 3 Downregulation in Mycobacterium tuberculosis-Infected Macrophages Reprograms Mitochondrial Metabolism and Promotes Cell Death.
Academic Article Host immunity increases Mycobacterium tuberculosis reliance on cytochrome bd oxidase.
Academic Article Characterization of Drug-Resistant Lipid-Dependent Differentially Detectable Mycobacterium tuberculosis.
Academic Article An improved statistical method to identify chemical-genetic interactions by exploiting concentration-dependence.
Academic Article Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice.
Academic Article REL and BHLHE40 Variants Are Associated with IL-12 and IL-10 Responses and Tuberculosis Risk.
Academic Article Chemical-genetic interaction mapping links carbon metabolism and cell wall structure to tuberculosis drug efficacy.
Academic Article Cell Wall Damage Reveals Spatial Flexibility in Peptidoglycan Synthesis and a Nonredundant Role for RodA in Mycobacteria.
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  • Mycobacterium