bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Inflammation, Organ Damage, and Oxidant Stress Induced by
Salmonella enterica
Serovar Muenchen Flagellin and Serovar Enteritidis Lipopolysaccharide
Authors: Liaudet Lucas , Murthy Kanneganti G. K. , Mabley Jon G. , Pacher Pál , Soriano Francisco G. , Salzman Andrew L. , Szabó Csaba 
Published: July 2002

ABSTRACT

Gram-negative sepsis is related to the activation of interconnected inflammatory cascades in response to bacteria and their products. Recent work showed that flagellin, the monomeric subunit of bacterial flagella, triggers innate immune responses mediated by Toll-like receptor 5. Here, we compared the effects of
Salmonella enterica
serovar Enteritidis lipopolysaccharide (LPS) and recombinant
Salmonella enterica
serovar Muenchen flagellin administered intravenously (100 μg) to mice. Flagellin and LPS both elicited a prototypical systemic inflammatory response, with increased levels of tumor necrosis factor alpha, gamma interferon, interleukin 6 and 10, and nitrate in plasma. Flagellin induced a widespread oxidative stress, evidenced by an increase in malondialdehyde and a decrease in reduced glutathione in most organs, as well as liver (increased plasma aminotransferases), but not renal, injury. Alternatively, LPS resulted in a less severe oxidative stress and triggered renal, but not liver, damage. Sequestration of polymorphonuclear neutrophils (increased myeloperoxidase activity) in the lungs was observed with both toxins, while only LPS recruited neutrophils in the gut. In additional experiments, the simultaneous administration of small doses of LPS and flagellin (10 μg) induced a synergistic enhancement of the production of proinflammatory cytokines. Our data support a novel concept implicating flagellin as a mediator of systemic inflammation, oxidant stress, and organ damage induced by gram-negative bacteria.
icmTIs Essential for Pore Formation-Mediated Egress ofLegionella pneumophilafrom Mammalian and Protozoan Cells
Authors: Molmeret Maelle , Alli O. A. Terry , Zink Steven , Flieger Antje , Cianciotto Nicholas P. , Kwaik Yousef Abu 
Published: July 2002

ABSTRACTThe final step of the intracellular life cycle ofLegionella pneumophilaand other intracellular pathogens is their egress from the host cell after termination of intracellular replication. We have previously isolated five spontaneous mutants ofL. pneumophilathat replicate intracellularly similar to the wild-type strain but are defective in pore formation-mediated cytolysis and egress from mammalian and protozoan cells, and the mutants have been designatedrib(release of intracellular bacteria). Here, we show that theribmutants are not defective in the activity of enzymes secreted through the type II secretion system, including phospholipase A, lysophospholipase A, and monoacylglycerol lipase, although they are potential candidates for factors that lyse host cell membranes. In addition, thepilDandlspGmutants, which are defective in the type II secretion system, are not defective in the pore-forming toxin. We show that all fiveribmutants have an identical point mutation (deletion) following a stretch of poly(T) in theicmTgene. Spontaneous revertants of theribmutants, due to an insertion of a nucleotide following the poly(T) stretch inicmT,have been isolated and shown to have regained the wild-type phenotype. We constructed anicmTinsertion mutant (AA100kmT) in the chromosome of the wild-type strain by allelic exchange. The AA100kmT mutant was as defective as theribmutant in pore formation-mediated cytolysis and egress from mammalian and protozoan cells. Both theribmutant and the AA100kmT mutant were complemented by theicmTgene for their phenotypic defect.rtxA, a gene that is thought to have a minor role in pore formation, was not involved in pore formation-mediated cytolysis and egress from mammalian and protozoan cells. We conclude that theicmTgene is essential for pore formation-mediated lysis of mammalian and protozoan cells and the subsequent bacterial egress.
Differential Binding of Host Complement Inhibitor Factor H byBorrelia burgdorferiErp Surface Proteins: a Possible Mechanism Underlying the Expansive Host Range of Lyme Disease Spirochetes
Authors: Stevenson Brian , El-Hage Nazira , Hines Melissa A. , Miller Jennifer C. , Babb Kelly 
Published: July 2002

ABSTRACTThe Lyme disease spirochete,Borrelia burgdorferi, is capable of infecting a wide variety of vertebrates. This broad host range implies thatB. burgdorferipossesses the ability to contravene the immune defenses of many potential hosts.B. burgdorferiproduces multiple different Erp proteins on its outer membrane during mammalian infection. It was reported previously that one Erp protein can bind human factor H (J. Hellwage, T. Meri, T. Heikkilä, A. Alitalo, J. Panelius, P. Lahdenne, I. J. T. Seppälä, and S. Meri, J. Biol. Chem. 276:8427–8435, 2001). In this paper we report that the ability to bind the complement inhibitor factor H is a general characteristic of Erp proteins. Furthermore, each Erp protein exhibits different relative affinities for the complement inhibitors of various potential animal hosts. The data suggest that the presence of multiple Erp proteins on the surface can allow a singleB. burgdorferibacterium to resist complement-mediated killing in any of the wide range of potential hosts that it might infect. Thus, Erp proteins likely contribute to the persistence ofB. burgdorferiin nature and to the ability of this bacterium to cause Lyme disease in humans and other animals.
Fas Ligand-Expressing B-1a Lymphocytes Mediate CD4+-T-Cell Apoptosis during Schistosomal Infection: Induction by Interleukin 4 (IL-4) and IL-10
Authors: Lundy Steven K. , Boros Dov L. 
Published: July 2002

ABSTRACTA previous study of the murine model ofSchistosoma mansoniinfection has implicated splenic CD19+B lymphocytes as Fas ligand (FasL)-bearing mediators of CD4+T-lymphocyte apoptosis. The present study shows that B-cell deficiency leads to decreased CD4+T-cell apoptosis during infection and compares FasL expression and killer function of B-1a- and CD5−B-lymphocyte subsets. B-1a cells from uninfected mice displayed constitutive expression of FasL compared with that of CD5−B cells. FasL expression was enhanced following worm egg deposition and antigenic stimulation on both subsets of B cells. Purified B-1a cells from uninfected mice were potent effectors of CD4+T-cell apoptosis, and the killing effect was enhanced during schistosome infection. FasL expression by splenic B cells required CD4+-T-cell help that was replaced by addition of culture supernatants from antigen-stimulated splenocytes of infected mice. The culture-supernatant-stimulated FasL expression was inhibited by anti-interleukin 10 (IL-10) and anti-IL-4 antibodies. Culture of purified B cells with recombinant IL-4 (rIL-4), rIL-10, and soluble egg antigens (SEA) led to increased expression of FasL on B-1a cells. These results suggest that FasL-expressing, splenic B-1a cells are important mediators of SEA-stimulated CD4+-T-cell apoptosis and that maximal FasL expression on B-1a cells is dependent on antigenic stimulation and the presence of IL-4 and IL-10.
Transcriptional Regulators Cph1p and Efg1p Mediate Activation of the
Candida albicans
Virulence Gene
SAP5
during Infection
Authors: Staib Peter , Kretschmar Marianne , Nichterlein Thomas , Hof Herbert , Morschhäuser Joachim 
Published: July 2002

ABSTRACT

The opportunistic fungal pathogen
Candida albicans
can cause superficial as well as systemic infections. Successful adaptation to the different host niches encountered during infection requires coordinated expression of various virulence traits, including the switch between yeast and hyphal growth forms and secretion of aspartic proteinases. Using an in vivo expression technology that is based on genetic recombination as a reporter of gene activation during experimental candidiasis in mice, we investigated whether two signal transduction pathways controlling hyphal growth, a mitogen-activated protein kinase cascade ending in the transcriptional activator Cph1p and a cyclic AMP-dependent regulatory pathway that involves the transcription factor Efg1p, also control expression of the
SAP5
gene, which encodes one of the secreted aspartic proteinases and is induced by host signals soon after infection. Our results show that both transcriptional regulators are important for
SAP5
activation in vivo.
SAP5
expression was reduced in a
cph1
mutant, although filamentous growth in infected tissue was not detectably impaired.
SAP5
expression was also reduced, but not eliminated, in an
efg1
null mutant, although this strain grew exclusively in the yeast form in infected tissue, demonstrating that in contrast to in vitro conditions,
SAP5
activation during infection does not depend on growth of
C. albicans
in the hyphal form. In a
cph1 efg1
double mutant, however,
SAP5
expression in infected mice was almost completely eliminated, suggesting that the two signal transduction pathways are important for
SAP5
expression in vivo. The avirulence of the
cph1 efg1
mutant seemed to be caused not only by the inability to form hyphae but also by a loss of expression of additional virulence genes in the host.
Transcript Heterogeneity of the
p44
Multigene Family in a Human Granulocytic Ehrlichiosis Agent Transmitted by Ticks
Authors: Zhi Ning , Ohashi Norio , Tajima Tomoko , Mott Jason , Stich Roger W. , Grover Debra , Telford Sam R. , Lin Quan , Rikihisa Yasuko 
Published: July 2002

ABSTRACT

Human granulocytic ehrlichiosis (HGE) is an emerging tick-borne zoonosis caused by a strain of
Anaplasma phagocytophila
called the HGE agent, an obligatory intracellular bacterium. The agent expresses immunodominant 44-kDa outer membrane proteins (P44s) encoded by a multigene family. The present study established an experimental process for transmission of the HGE agent from infected mice (a reservoir model) to nymphal
Ixodes scapularis
ticks (a biological vector) and subsequently to horses (a patient model) by the adult infected ticks. Overall, a total of 20 different
p44
transcripts were detected in the mammals, ticks, and cell cultures. Among them, a transcript from a
p44
-
18
gene was major at acute stage in mice and horses but minor in ticks. Both mRNA and protein produced from the
p44
-
18
gene were detected in the HGE agent cultivated in HL-60 cells at 37°C, but their expression levels decreased in the organisms cultivated at 24°C, suggesting that temperature is one of the factors that influence the expression of members of the
p44
multigene family. Several additional
p44
transcripts that were not detected in the mammals at the acute stage of infection were detected in ticks. Phylogenetic analysis of the 20 different
p44
transcripts revealed that the major transcripts found in mammals and ticks were distinct, suggesting a difference in surface properties between populations of the HGE agent in different host environments. The present study provides new information for understanding the role of the
p44
multigene family in transmission of the HGE agent between mammals and ticks.
Lack of Fusion of Azurophil Granules with Phagosomes during Phagocytosis ofMycobacterium smegmatisby Human Neutrophils Is Not Actively Controlled by the Bacterium
Authors: Cougoule Céline , Constant Patricia , Etienne Gilles , Daffé Mamadou , Maridonneau-Parini Isabelle 
Published: July 2002

ABSTRACTBiogenesis of phagolysosomes is a very rapid event in neutrophils which takes place with nascent unclosed phagosomes, leading to the release of lysosomal enzymes such as β-glucuronidase in the extracellular medium. We have previously shown that, under nonopsonic conditions, both pathogenic and nonpathogenic mycobacteria uncouple phagocytosis from fusion of azurophil granules (specialized secretory lysosomes) with phagosomes. In the present study we questioned whether they actively act on neutrophils to block this process or use phagocytic receptors that negatively control the biogenesis of phagolysosomes. As for live unicellularMycobacterium smegmatis, we observed that nonopsonic phagocytosis of heat-killed mycobacteria did not induce the release of β-glucuronidase, indicating thatM. smegmatisdoes not actively act on the fusion process in neutrophils. In contrast, phagocytosis of unicellularM. smegmatisopsonized in immune serum or that of small nonopsonized mycobacterial aggregates restored the biogenesis of phagolysosomes. Aggregates were internalized in a CR3- and cholesterol-dependent manner as unicellular mycobacteria. However, aggregates but not unicellular bacteria triggered F-actin and Hck recruitment at the phagosomes, events that have been associated with lysosome fusion. Thus, we propose thatM. smegmatisdoes not actively control the fusion of azurophil granules at early time points postinfection and that mycobacterial aggregates recruit large clusters of receptors at the neutrophil surface which could trap proteins implicated in the biogenesis of phagolysosomes.
Pseudomonas aeruginosa
Quorum-Sensing Systems May Control Virulence Factor Expression in the Lungs of Patients with Cystic Fibrosis
Authors: Erickson David L. , Endersby Ryan , Kirkham Amanda , Stuber Kent , Vollman Dolina D. , Rabin Harvey R. , Mitchell Ian , Storey Douglas G. 
Published: July 2002

ABSTRACT

Individuals with cystic fibrosis (CF) are commonly colonized with
Pseudomonas aeruginosa
. The chronic infections caused by
P. aeruginosa
are punctuated by acute exacerbations of the lung disease, which lead to significant morbidity and mortality. As regulators of virulence determinants,
P. aeruginosa
quorum-sensing systems may be active in the chronic lung infections associated with CF. We have examined the levels of autoinducer molecules and transcript accumulation from the bacterial populations found in the lungs of patients with CF. We detected biologically active levels of
N
-(3-oxododecanoyl)-
l
-homoserine (3-oxo-C12-HSL) and
N
-butyryl-
l
-homoserine lactone (C4-HSL) in sputum from CF patients. Interestingly, it appears that C4-HSL is less frequently detected than 3-oxo-C12-HSL in the lungs of patients with CF. We also examined the transcription of the autoinducer synthase gene
lasI
and showed that it is frequently expressed in the lungs of patients with CF. We observed a significant correlation between the expression of
lasI
and four target genes of the Las quorum-sensing system. Taken together, our results indicate that quorum-sensing systems are active and may control virulence factor expression in the lungs of patients with CF.
Phase I Evaluation of Δ
virG Shigella sonnei
Live, Attenuated, Oral Vaccine Strain WRSS1 in Healthy Adults
Authors: Kotloff Karen L. , Taylor David N. , Sztein Marcelo B. , Wasserman Steven S. , Losonsky Genevieve A. , Nataro James P. , Venkatesan Malabi , Hartman Antoinette , Picking William D. , Katz David E. , Campbell James D. , Levine Myron M. , Hale Thomas L. 
Published: July 2002

ABSTRACT

We conducted a phase I trial with healthy adults to evaluate WRSS1, a live, oral Δ
virG Shigella sonnei
vaccine candidate. In a double-blind, randomized, dose-escalating fashion, inpatient volunteers received a single dose of either placebo (
n
= 7) or vaccine (
n
= 27) at 3 × 10
3
CFU (group 1), 3 × 10
4
CFU (group 2), 3 × 10
5
CFU (group 3), or 3 × 10
6
CFU (group 4). The vaccine was generally well tolerated, although a low-grade fever or mild diarrhea occurred in six (22%) of the vaccine recipients. WRSS1 was recovered from the stools of 50 to 100% of the vaccinees in each group. The geometric mean peak anti-lipopolysaccharide responses in groups 1 to 4, respectively, were 99, 39, 278, and 233 for immunoglobulin (IgA) antibody-secreting cell counts; 401, 201, 533, and 284 for serum reciprocal IgG titers; and 25, 3, 489, and 1,092 for fecal IgA reciprocal titers. Postvaccination increases in gamma interferon production in response to
Shigella
antigens occurred in some volunteers. We conclude that WRSS1 vaccine is remarkably immunogenic in doses ranging from 10
3
to 10
6
CFU but elicits clinical reactions that must be assessed in further volunteer trials.
Construction of atetR-IntegratedSalmonella entericaSerovar Typhi CVD908 Strain That Tightly Controls Expression of the Major Merozoite Surface Protein ofPlasmodium falciparumfor Applications in Human Vaccine Production
Authors: Qian Feng , Pan Weiqing 
Published: July 2002

ABSTRACTAttenuatedSalmonellastrains are an attractive live vector for delivery of a foreign antigen to the human immune system. However, the problem with this vector lies with plasmid segregation and the low level of expression of the foreign gene in vivo when constitutive expression is employed, leading to a diminished immune response. We have established inducible expressions of foreign genes in theSalmonella entericaserovar Typhi CVD908 vaccine strain using the tetracycline response regulatory promoter. To set up this system, a tetracycline repressor (tetR) was integrated into a defined ΔaroClocus of the chromosome via suicide plasmid pJG12/tetR-neo. To remove theneogene conferring kanamycin resistance from the locus, acreexpression vector under the control of the tetracycline response promoter was transformed into the clone; expression of the Cre recombinase excised theneogene and generated the end strain CVD908-tetR. Expression of the luciferase reporter gene in this strain is dependent on the presence of tetracycline in the medium and can be regulated up to 4,773-fold. Moreover, the tightly controlled expression of major merozoite surface protein 1 (MSP1) and parts ofPlasmodium falciparumwas achieved, and the product yield was increased when the inducible expression system was employed. Inoculation of bacteria harboring plasmid pZE11/MSP142in mice produced the protein in liver and spleen controlled by the inducer. The persistence of the plasmid-carrying bacteria in mice was determined. Peak colonization of both liver and spleen was detected on the third day postinoculation and was followed by a decline in growth curves. After 14 days postinfection, the majority of the bacteria (>90%) recovered from the liver and spleen of the mice retained the plasmid when expression was induced; this clearly indicated that stability of the expression vector in vivo was improved by inducible expression. Establishment of the regulatory system in the vaccine strain may broaden the range of its use by enhancing plasmid stability and expression levels in vivo. Moreover, the availability of the vaccine strain inducibly expressing the entire MSP1 provides possibilities for examining its immunogenicity, particularly the cellular response in animal models.
Campylobacter Protein Glycosylation Affects Host Cell Interactions
Authors: Szymanski Christine M. , Burr Donald H. , Guerry Patricia 
Published: July 2002

ABSTRACT

Campylobacter jejuni
81-176
pgl
mutants impaired in general protein glycosylation showed reduced ability to adhere to and invade INT407 cells and to colonize intestinal tracts of mice.
NovelAeromonas hydrophilaPPD134/91 Genes Involved in O-Antigen and Capsule Biosynthesis
Authors: Zhang Y. L. , Arakawa E. , Leung K. Y. 
Published: July 2002

ABSTRACTThe sequences of the O-antigen and capsule gene clusters of the virulentAeromonas hydrophilastrain PPD134/91 were determined. The O-antigen gene cluster is 17,296 bp long and comprises 17 genes. Seven pathway genes for the synthesis of rhamnose and mannose, six transferase genes, one O unit flippase gene, and one O-antigen chain length determinant gene were identified by amino acid sequence similarity. PCR and Southern blot analysis were performed to survey the distribution of these 17 genes among 11A. hydrophilastrains of different serotypes.A. hydrophilaPPD134/91 might belong to serotype O:18, as represented by JCM3980; it contained all the same O-antigen genes as JCM3980 (97 to 100% similarity at the DNA and amino acid levels). The capsule gene cluster ofA. hydrophilaPPD134/91 is 17,562 bp long and includes 13 genes, which were assembled into three distinct regions similar to those of the group II capsule gene cluster ofEscherichia coliand other bacteria. Regions I and III contained four and two capsule transport genes, respectively. Region II had five genes which were highly similar to capsule synthesis pathway genes found in other bacteria. Both the purified O-antigen and capsular polysaccharides increased the ability of the avirulentA. hydrophilastrain PPD35/85 to survive in naïve tilapia serum. However, the purified surface polysaccharides had no inhibitory effect on the adhesion ofA. hydrophilaPPD134/91 to carp epithelial cells.
Chlamydia pneumoniaeInfection Induces Differentiation of Monocytes into Macrophages
Authors: Yamaguchi Hiroyuki , Haranaga Shusaku , Widen Ray , Friedman Herman , Yamamoto Yoshimasa 
Published: July 2002

ABSTRACTMigration and differentiation of monocytes to the intima of blood vessels may be a crucial first step in the development of atherosclerosis associated withChlamydia(Chlamydophila)pneumoniae. However, the involvement ofC. pneumoniaeinfection in such steps is not clear. In the present study, therefore, the differentiation-inducing activity ofC. pneumoniaeto monocytes was examined. Human THP-1 monocytic cell line cells were infected withC. pneumoniae, and the differentiation of monocytes to macrophages was assessed by cell morphology, phagocytic activity, and expression of a cell surface adhesion molecule. The monocytic cells infected with viable bacteria markedly differentiated into macrophages associated with diffused cell morphology, increased uptake of polystyrene beads and increased ICAM-1 (intercellular adhesion molecule 1) expression on the cell surfaces. Heat-killed bacteria did not induce any morphological changes or increase of phagocytosis, but they did induce an increase of cell surface ICAM-1 expressions in THP-1 monocytic cells. The antibiotic minocycline treatment of infected cells resulted in marked inhibition of the cell differentiation as well asC. pneumoniaegrowth in the cells, but not ICAM-1 expression. In addition, the experiments with human peripheral blood monocytes infected withC. pneumoniaealso showed the differentiation of macrophages assessed by morphological change and phagocytic activity. These results indicate thatC. pneumoniaeinfection may directly induce the differentiation of monocytes to macrophages. However, antigenic stimulation of monocytes with bacteria may not be sufficient for a full macrophage differentiation.
Antigenic Diversity inEimeria maximaand the Influence of Host Genetics and Immunization Schedule on Cross-Protective Immunity
Authors: Smith Adrian L. , Hesketh Patricia , Archer Andrew , Shirley Martin W. 
Published: July 2002

ABSTRACTEimeriaspp. are a group of highly successful intracellular protozoan parasites that develop within enterocytes.Eimeria maximafrom the chicken is characterized by high immunogenicity (a small priming infection gives complete immunity to subsequent homologous challenge) and naturally occurring antigenically variant populations that do not completely cross-protect. In this study we examined the expression of antigenic diversity inE. maxima, as manifested by cross-strain protection in a series of inbred chicken lines. The IAH line of Light Sussex chickens and all lines of inbred White Leghorns were susceptible to primary infections with either of two strains (H and W) ofE. maximaand were protected completely against challenge with the homologous strain of parasite. The extent of cross-protection against the heterologous parasite strain varied from 0 to almost 100% depending on host genetics. Interestingly, in one inbred line of chickens (line 15I) the cross-protective phenotype was directional and intensely influenced by the infection history of the host. The basis for the observed variation in cross-protection is not known, but our results suggest that the major histocompatibility complex is not a major genetic component of the phenotype. These results are discussed in relation to the number of protective antigens presented by complex pathogens and the development of immunoprotective responses in hosts of different genetic backgrounds.