A5046949754- Legionella and Acanthamoeba research
- Vibrio bacteria research studies
- Bacterial Genetics and Biotechnology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bacterial biofilms and quorum sensing
- Enzyme Structure and Function
- Antibiotic Resistance in Bacteria
- Drug Transport and Resistance Mechanisms
- Water Treatment and Disinfection
- Heme Oxygenase-1 and Carbon Monoxide
- Bacteriophages and microbial interactions
- Amino Acid Enzymes and Metabolism
- Protein Structure and Dynamics
- Parasitic Infections and Diagnostics
- RNA and protein synthesis mechanisms
- Enzyme Production and Characterization
- Cancer Research and Treatments
- Metabolism and Genetic Disorders
- Neonatal Health and Biochemistry
- Pediatric Hepatobiliary Diseases and Treatments
- Lipid Membrane Structure and Behavior
- DNA Repair Mechanisms
- Antifungal resistance and susceptibility
- Genomics and Phylogenetic Studies
- Pneumocystis jirovecii pneumonia detection and treatment
University of Chicago
2013-2023
Manhattan College
2020
Columbia University Irving Medical Center
2005-2014
Columbia University
1999-2014
Argonne National Laboratory
2014
Cummings Foundation
2012
Howard Hughes Medical Institute
2005
Tel Aviv University
2004
Institut Pasteur
1975-2004
Roswell Park Comprehensive Cancer Center
2004
A 22-kb DNA locus of Legionella pneumophila is described that contains 18 genes, 16 which are required for macrophage killing ( icm genes). In this paper two previously loci were linked by the discovery five genes located between loci. Four newly icmMLKE ) and one dispensable. The appeared to be organized as six individual icmR , icmQ icmG icmC icmD, icmF ), four operons icmTS icmPO icmJB ). icmP icmO icmL icmE show significant sequence similarity plasmid involved in conjugation, whereas...
Cryptococcus neoformans ( Cn ) is a soil fungus that causes life-threatening meningitis in immunocompromised patients and facultative intracellular pathogen capable of replication inside macrophages. The mechanism by which environmental fungi acquire maintain virulence for mammalian hosts unknown. We hypothesized the survival strategies after ingestion macrophages amoebae were similar. Microscopy, fungal killing assays, phagocytosis assays revealed phagocytosed replicates Acanthamoeba...
We present the genomic sequence of Legionella pneumophila, bacterial agent Legionnaires' disease, a potentially fatal pneumonia acquired from aerosolized contaminated fresh water. The genome includes 45-kilobase pair element that can exist in chromosomal and episomal forms, selective expansions important gene families, genes for unexpected metabolic pathways, previously unknown candidate virulence determinants. highlight may account Legionella's ability to survive protozoa, mammalian...
Gil Segal, Howard Shuman and colleagues sequence the genomes of 38 Legionella species analyze 5,885 predicted effector proteins. Their analysis identifies a core set seven effectors shared by all numerous previously unidentified conserved domains. Infection human pathogen pneumophila relies on translocation ∼300 virulence proteins, termed effectors, which manipulate host cell processes. However, almost no information exists regarding in other pathogens. Here we sequenced, assembled...
Gallium disrupts bacterial iron metabolism and treats infections in mice patients with chronic airway infections.
Legionella pneumophila, the causative agent of Legionnaires' disease, evades phago-lysosome fusion in mammalian and protozoan hosts to create a suitable niche for intracellular replication. To modulate vesicle trafficking pathways, L. pneumophila translocates effector proteins into eukaryotic cells through Type IVB macro-molecular transport system called Icm-Dot system. In this study, we employed fluorescence-based translocation assay show that 33 previously identified eukaryotic-like genes...
Legionella pneumophila was mutagenized with Tn903dIIlacZ, and a collection of mutants screened for defects in macrophage killing (Mak-). Of 4,564 independently derived mutants, 55 (1.2%) showed reduced or complete lack the ability to kill HL-60-derived human macrophages. Forty-nine Mak- could be assigned one 16 DNA hybridization groups. Only group (9 10 members) complemented by fragment containing icm dot, two recently described L. loci that are required killing. Phenotypic analysis none...
The legionnaires' disease bacterium, Legionella pneumophila, is a facultative intracellular parasite. Its interaction with phagocytes has characteristics in common several other parasites. Critical aspects of L. pneumophila multiplication are evasion lysosomal host cell defenses and the presence nutritionally appropriate environment. Following phagocytosis, wild-type multiply within specialized phagosome which does not fuse secondary lysosomes. Mutants have lost ability to grow no longer...
ABSTRACT In previous reports we described a 22-kb Legionella pneumophila chromosomal locus containing 18 genes. Thirteen of these genes ( icmT , - R Q P O M L K E C D J and B ) were found to be completely required for intracellular growth killing human macrophages. Three icmS G F partially required, two lphA tphA dispensable Here, analyzed the requirement in protozoan host Acanthamoeba castellanii well-established important environmental L. . We that all are macrophages also A. However,...
Legionella pneumophila, the bacterial agent of legionnaires' disease, replicates intracellularly within a specialized vacuole mammalian and protozoan host cells. Little is known about except that Icm/Dot type IV secretion system essential for its formation maintenance. The genome database contains two open reading frames encoding polypeptides (LepA LepB) with predicted coiled-coil regions weak homology to SNAREs; these are delivered cells by an Icm/Dot-dependent mechanism. Analysis mutant...
Maltose transport across the cytoplasmic membrane of Escherichia coli is dependent on presence a periplasmic maltose-binding protein (MBP), product malE gene. The products malF, malG, and malK genes form membrane-associated complex that catalyzes hydrolysis ATP to provide energy for event. Previously, mutants were isolated had gained ability grow maltose in absence MBP. After reconstitution into proteoliposomes, measurement ATPase activity wild-type mutant complexes MBP revealed hydrolyzed...
ABSTRACT Intracellular pathogens exploit host cell functions to create a replication niche inside eukaryotic cells. The causative agent of Legionnaires' disease, the γ-proteobacterium Legionella pneumophila , resides and replicates within modified vacuole protozoan mammalian L. translocates effector proteins into cells through Icm-Dot complex, specialized type IVB secretion system that is required for intracellular growth. To find out if some may have been acquired interdomain horizontal...
Legionella pneumophila invades and replicates intracellularly in human protozoan hosts. The bacteria use the Icm/Dot type IVB secretion system to translocate effectors that inhibit phagosome maturation modulate host vesicle trafficking pathways. To understand how L. modulates organelle cells, we carried out pathogen effector protein screening yeast, identifying genes produced membrane [vacuole sorting (VPS)] defects yeast. We identified four DNA fragments perturb of vacuolar proteins. Three...
Summary Legionella pneumophila , the causative agent of Legionnaires’ disease and related pneumonias, infects, replicates within eventually kills human macrophages. A key feature intracellular lifestyle is ability organism to replicate a specialized phagosome which does not fuse with Iysosomes or acidify. Avirulent mutants that are defective in multiplication host‐cell killing unable prevent phagosome–Iysosome fusion. In previous study, 12kb fragment L. genome containing icm locus...
Legionella and Coxiella are intracellular pathogens that use the virulence-related Icm/Dot type-IVB secretion system to translocate effector proteins into host cells during infection. These effectors were previously shown contain a C-terminal signal required for their translocation. In this research, we implemented hidden semi-Markov model characterize amino acid composition of signal, thus providing comprehensive computational signal. This accounts dependencies among sites captures spatial...
Closely similar but nonidentical NH2-terminal amino acid sequences have been reported for a protein or proteins in human neutrophils whose bioactivities is/are diverse (as serine protease, antibiotic, and Wegener's granulomatosis autoantigen) that share(s) several features: localization the azurophil granules, molecular mass of approximately 29 kD, reactivity with diisopropylfluorophosphate, ability to degrade elastin. We previously purified one such entity, termed p29b. Using monospecific...
The active transport of maltose in Escherichia coli requires the products five genes. These include a water-soluble periplasmic maltose-binding protein, three cytoplasmic membrane proteins, and an outer protein. In order to evaluate role protein transport, nonpolar internal deletion structural gene for was constructed. A strain which contains this is unable grow on at external concentration 25 mM, even when remaining components system are synthesized constitutively. This demonstrates that...
We isolated mutants of Escherichia coli in which the maltose-binding protein (MBP) is no longer required for growth on maltose as sole source carbon and energy. These were selected Mal+ revertants a strain carries deletion MBP structural gene, malE. In one class these mutants, transported into cell independently by remaining components system. The mutations strains map either malF or malG. genes code two cytoplasmic membrane transport some actually inhibits transport. demonstrate that still...
Escherichia coli strains have been isolated that produce hybrid proteins comprised of an NH2-terminal sequence from the lamB gene product (an outer membrane protein) and a major portion COOH-terminal beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23; cytoplasmic protein). These exhibit activity. One such strain, pop 3105, produces protein containing very little protein; is found in cytoplasm. The second 3186, contains much more substantial fraction activity membrane,...