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Full-Text Articles in Medicine and Health Sciences

Identification And Characterization Of Spcu, A Chaperone Required For Efficient Secretion Of The Exou Cytotoxin, Viviane Finck-Barbançon, Timothy L. Yahr, Dara W. Frank Dec 1998

Identification And Characterization Of Spcu, A Chaperone Required For Efficient Secretion Of The Exou Cytotoxin, Viviane Finck-Barbançon, Timothy L. Yahr, Dara W. Frank

Dartmouth Scholarship

In recent studies, we have shown that Pseudomonas aeruginosa strains that are acutely cytotoxic in vitro damage the lung epithelium in vivo. Genetic analysis indicated that the factor responsible for acute cytotoxicity was controlled by ExsA and therefore was part of the exoenzyme S regulon. The specific virulence determinant responsible for epithelial damage in vivo and cytotoxicity in vitro was subsequently mapped to the exoU locus. The present studies are focused on a genetic characterization of the exoU locus. Northern blot analyses and complementation experiments indicated that a region downstream of exoU was expressed and that the expression of this …


The Seca Subunit Of Escherichia Coli Preprotein Translocase Is Exposed To The Periplasm, Jerry Eichler, William Wickner Nov 1998

The Seca Subunit Of Escherichia Coli Preprotein Translocase Is Exposed To The Periplasm, Jerry Eichler, William Wickner

Dartmouth Scholarship

SecA undergoes conformational changes during translocation, inserting domains into and across the membrane or enhancing the protease resistance of these domains. We now show that some SecA bound at SecYEG is accessible from the periplasm to a membrane-impermeant probe in cells with a permeabilized outer membrane but an intact plasma membrane.


Exoy, An Adenylate Cyclase Secreted By The Pseudomonas Aeruginosa Type Iii System, Timothy L. Yahr, Amy J. Vallis, Michael Hancock, Joseph T. Barbieri, Dara W. Frank Nov 1998

Exoy, An Adenylate Cyclase Secreted By The Pseudomonas Aeruginosa Type Iii System, Timothy L. Yahr, Amy J. Vallis, Michael Hancock, Joseph T. Barbieri, Dara W. Frank

Dartmouth Scholarship

The exoenzyme S regulon is a set of coordinately regulated virulence genes of Pseudomonas aeruginosa. Proteins encoded by the regulon include a type III secretion and translocation apparatus, regulators of gene expression, and effector proteins. The effector proteins include two enzymes with ADP-ribosyltransferase activity (ExoS and ExoT) and an acute cytotoxin (ExoU). In this study, we identified ExoY as a fourth effector protein of the regulon. ExoY is homologous to the extracellular adenylate cyclases of Bordetella pertussis (CyaA) and Bacillus anthracis (EF). The homology among the three adenylate cyclases is limited to two short regions, one of which possesses an …


Identification Of Putative Cytoskeletal Protein Homologues In The Protozoan Host Hartmannella Vermiformis As Substrates For Induced Tyrosine Phosphatase Activity Upon Attachment To The Legionnaires' Disease Bacterium, Legionella Pneumophila, Chandrasekar Venkataraman, Lian-Yang Gao, Subbarao Bondada, Yousef Abu Kwaik Aug 1998

Identification Of Putative Cytoskeletal Protein Homologues In The Protozoan Host Hartmannella Vermiformis As Substrates For Induced Tyrosine Phosphatase Activity Upon Attachment To The Legionnaires' Disease Bacterium, Legionella Pneumophila, Chandrasekar Venkataraman, Lian-Yang Gao, Subbarao Bondada, Yousef Abu Kwaik

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Legionnaires' disease bacterium, Legionella pneumophila, is a facultative intracellular pathogen that invades and replicates within two evolutionarily distant hosts, free living protozoa and mammalian cells. Invasion and intracellular replication within protozoa are thought to be major factors in the transmission of Legionnaires' disease. We have recently reported the identification of a galactose/N-acetyl-d-galactosamine (Gal/GalNAc) lectin in the protozoan host Hartmannella vermiformis as a receptor for attachment and invasion by L. pneumophila (Venkataraman, C., B.J. Haack, S. Bondada, and Y.A. Kwaik. 1997. J. Exp. Med. 186:537–547). In this report, we extended our studies to the …


Expression Of Toxoplasma Gondii-Specific Heat Shock Protein 70 During In Vivo Conversion Of Bradyzoites To Tachyzoites, Neide M. Silva, Ricardo T. Gazzinelli, Deise A. O. Silva, Eloisa A. V. Ferro, Lloyd H. Kasper, Jose R. Mineo Aug 1998

Expression Of Toxoplasma Gondii-Specific Heat Shock Protein 70 During In Vivo Conversion Of Bradyzoites To Tachyzoites, Neide M. Silva, Ricardo T. Gazzinelli, Deise A. O. Silva, Eloisa A. V. Ferro, Lloyd H. Kasper, Jose R. Mineo

Dartmouth Scholarship

Stage conversion between bradyzoites and tachyzoites was investigated in C57BL/6 mice chronically infected with the ME-49 strain of Toxoplasma gondii. In order to promote bradyzoite-tachyzoite conversion, mice were treated in vivo with neutralizing doses of anti-gamma interferon (IFN-gamma) or anti-tumor necrosis factor alpha (TNF-alpha) antibodies. Expression of parasite-specific antigens SAG-1, SAG-2, and heat shock protein 70 (Hsp-70) was visualized in the central nervous system by immunocytochemistry and measured by photometric assay. The immunosuppressive effect of anti-IFN-gamma or anti-TNF-alpha treatment was immediate, leading to parasite stage conversion as indicated by the increased expression of tachyzoite-specific antigens (SAG-1 and SAG-2) and by …


Expression Of Constitutively Active Raf-1 In The Mitochondria Restores Antiapoptotic And Leukemogenic Potential Of A Transformation-Deficient Bcr/Abl Mutant., P Salomoni, M A Wasik, R F Riedel, K Reiss, J K Choi, T Skorski, B Calabretta Jun 1998

Expression Of Constitutively Active Raf-1 In The Mitochondria Restores Antiapoptotic And Leukemogenic Potential Of A Transformation-Deficient Bcr/Abl Mutant., P Salomoni, M A Wasik, R F Riedel, K Reiss, J K Choi, T Skorski, B Calabretta

Department of Microbiology and Immunology Faculty Papers

The oncogenic BCR/ABL protein protects hematopoietic cells from apoptosis induced by growth factor deprivation, but the mechanisms are only partially understood. A BCR/ABL mutant lacking amino acids 176-426 in the BCR domain (p185DeltaBCR) failed to protect interleukin 3-deprived 32Dcl3 myeloid precursor cells from apoptosis, although it possessed tyrosine kinase activity and was capable of activating the Ras-Raf-MAP kinase pathway. Compared to p185 wild-type transfectants, p185DeltaBCR-transfected cells showed markedly reduced levels of Bcl-2 and expressed the hypophosphorylated, proapoptotic form of BAD. Bcl-2 expression in the mitochondrial fraction of p185DeltaBCR cells was also markedly diminished and mitochondrial RAF was undetectable. In p185DeltaBCR …


The Sequential Role Of Lymphotoxin And B Cells In The Development Of Splenic Follicles, Mercedes Gonzalez, Fabienne Mackay, Jeffrey L. Browning, Marie H. Kosco-Vilbois, Randolph J. Noelle Apr 1998

The Sequential Role Of Lymphotoxin And B Cells In The Development Of Splenic Follicles, Mercedes Gonzalez, Fabienne Mackay, Jeffrey L. Browning, Marie H. Kosco-Vilbois, Randolph J. Noelle

Dartmouth Scholarship

The transfer of lymphocytes into severe combined immunodeficiency (SCID) mice induces a series of histological changes in the spleen, including the appearance of mature follicular dendritic cells (FDCs). Studies were undertaken to clarify the role of lymphotoxin (LT) in this process. The results show that SCID mice have a small and partially differentiated white pulp containing marginal zone and interdigitating dendritic cells, but lacking FDCs. Transferred spleen cells can segregate into T and B cell areas shortly after their injection to SCID mice. This ability is dependent on signaling through LT-β receptor (LT-βR), since blocking ligand–receptor interaction in recipient SCID …


Antigen-Specific Cd8+ T Cells Protect Against Lethal Toxoplasmosis In Mice Infected With Neospora Caninum, Lloyd H. Kasper, Imtiaz A. Khan Apr 1998

Antigen-Specific Cd8+ T Cells Protect Against Lethal Toxoplasmosis In Mice Infected With Neospora Caninum, Lloyd H. Kasper, Imtiaz A. Khan

Dartmouth Scholarship

Neospora caninum is a coccidial protozoan parasite that appears morphologically indistinguishable from Toxoplasma gondii and that infects a large range of mammals. Both inbred and outbred strains of mice exhibit a high degree of resistance to infection with N. caninum. Three inbred strains of mice (A/J, BALB/c, and C57BL/6) that were infected intraperitoneally with N. caninum were protected against a lethal challenge from T. gondii. Vaccine-induced protection was Neospora dose dependent. A rise in the CD8+ T-cell population in mice that had been vaccinated with N. caninum and challenged with T. gondii was observed. Adoptive transfer of CD8+ T-cell splenocytes …


Chlamydia Trachomatis Infection In The Female Reproductive Tract Of The Rat: Influence Of Progesterone On Infectivity And Immune Response, Charu Kaushic, Andrew D. Murdin, Brian J. Underdown, Charles R. Wira Mar 1998

Chlamydia Trachomatis Infection In The Female Reproductive Tract Of The Rat: Influence Of Progesterone On Infectivity And Immune Response, Charu Kaushic, Andrew D. Murdin, Brian J. Underdown, Charles R. Wira

Dartmouth Scholarship

As the most common cause of sexually transmitted disease in women, chlamydial infections can lead to pelvic inflammatory disease, infertility, and ectopic pregnancy. To better understand the role played by sex hormones in modulating the immune response of the genital tract to microbial infections, we have developed a rat model to study Chlamydia trachomatis infection. Inbred female Lewis rats were primed with progesterone and inoculated by intrauterine instillation of C. trachomatis (mouse pneumonitis strain MoPn) into each uterine horn. When infected animals were examined for the presence of chlamydial antigens 14 days postinfection, both the uterus and vagina were found …


Investigation Of The Roles Of Toxin-Coregulated Pili And Mannose-Sensitive Hemagglutinin Pili In The Pathogenesis Of Vibrio Cholerae O139 Infection, Carol O. Tacket, Ronald K. Taylor, Genevieve Losonsky, Yu Lim Feb 1998

Investigation Of The Roles Of Toxin-Coregulated Pili And Mannose-Sensitive Hemagglutinin Pili In The Pathogenesis Of Vibrio Cholerae O139 Infection, Carol O. Tacket, Ronald K. Taylor, Genevieve Losonsky, Yu Lim

Dartmouth Scholarship

In this study, adult volunteers were fed tcpA and mshA deletion mutants of V. cholerae O139 strain CVD 112 to determine the role of toxin-coregulated pili (TCP) and mannose-sensitive hemagglutinin (MSHA) in intestinal colonization. Eight of 10 volunteers who received CVD 112 or CVD 112 ΔmshA shed the vaccine strains in their stools; the geometric mean peak excretion for both groups was 1.4 × 105 CFU/g of stool. In contrast, only one of nine recipients of CVD 112 ΔtcpA shed vibrios in his stool (P < 0.01); during the first 24 h after inoculation, 3 × 102 CFU/g was recovered from this volunteer. All recipients of CVD …