bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunization with the
Chlamydia trachomatis
Mouse Pneumonitis Major Outer Membrane Protein by Use of CpG Oligodeoxynucleotides as an Adjuvant Induces a Protective Immune Response against an Intranasal Chlamydial Challenge
Authors: Pal Sukumar , Davis Heather L. , Peterson Ellena M. , de la Maza Luis M. 
Published: October 2002

ABSTRACT

Recently, we have shown that a vaccine consisting of a purified preparation of the
Chlamydia trachomatis
mouse pneumonitis (MoPn) major outer membrane protein (MOMP) and Freund's adjuvant can protect mice against a genital challenge. Here, we wanted to determine if CpG motifs could be used as an immune modulator to the MOMP to induce protection in mice against an intranasal (i.n.) challenge. One-week-old BALB/c mice were immunized intramuscularly and subcutaneously either once or three times at 2-week intervals with MOMP and CpG suspended in aluminum hydroxide (alum). Negative controls received ovalbumin, CpG, and alum. Positive controls were immunized i.n. with
C. trachomatis
MoPn elementary bodies (EB). Six weeks after the last immunization, mice were challenged i.n. with 10
4
inclusion-forming units (IFU) of the
C. trachomatis
MoPn serovar. Mice that received MOMP, CpG, and alum had a strong immune response, as shown by a high titer of serum antibodies to
Chlamydia
and significant lymphoproliferation of T-cells following stimulation with
C. trachomatis
EB. After the i.n. challenge mice immunized with MOMP, CpG, and alum showed significantly less body weight loss than the corresponding control mice immunized with ovalbumin, CpG, and alum. Ten days after the challenge the animals were euthanized, their lungs were weighed, and the numbers of IFU in the lungs were determined. The average weight of the lungs of the mice immunized with MOMP, CpG, and alum was significantly less than average weight of the lungs of the mice immunized with ovalbumin, CpG, and alum. Also, the average number of IFU recovered per mouse immunized with MOMP, CpG, and alum was significantly less than the average number of IFU per mouse detected in the mice inoculated with ovalbumin, CpG, and alum. In conclusion, our data show that CpG sequences can be used as an effective adjuvant with the
C. trachomatis
MoPn MOMP to elicit a protective immune response in mice against a chlamydial respiratory challenge.
The YadA Protein ofYersinia pseudotuberculosisMediates High-Efficiency Uptake into Human Cells under Environmental Conditions in Which Invasin Is Repressed
Authors: Eitel Julia , Dersch Petra 
Published: October 2002

ABSTRACTThe YadA protein is a major adhesin ofYersinia pseudotuberculosisthat promotes tight adhesion to mammalian cells by binding to extracellular matrix proteins. In this study, we first addressed the possibility of competitive interference of YadA and the major invasive factor invasin and found that expression of YadA in the presence of invasin affected neither the export nor the function of invasin in the outer membrane. Furthermore, expression of YadA promoted both bacterial adhesion and high-efficiency invasion entirely independently of invasin. Antibodies against fibronectin and β1integrins blocked invasion, indicating that invasion occurs via extracellular-matrix-dependent bridging between YadA and the host cell β1integrin receptors. Inhibitor studies also demonstrated that tyrosine and Ser/Thr kinases, as well as phosphatidylinositol 3-kinase, are involved in the uptake process. Further expression studies revealed thatyadAis regulated in response to several environmental parameters, including temperature, ion and nutrient concentrations, and the bacterial growth phase. In complex medium, YadA production was generally repressed but could be induced by addition of Mg2+. Maximal expression ofyadAwas obtained in exponential-phase cells grown in minimal medium at 37°C, conditions under which the invasin gene is repressed. These results suggest that YadA ofY. pseudotuberculosisconstitutes another independent high-level uptake pathway that might complement other cell entry mechanisms (e.g., invasin) at certain sites or stages during the infection process.
Streptococcal Inhibitor of Complement Inhibits Two Additional Components of the Mucosal Innate Immune System: Secretory Leukocyte Proteinase Inhibitor and Lysozyme
Authors: Fernie-King Barbara A. , Seilly David J. , Davies Alexandra , Lachmann Peter J. 
Published: October 2002

ABSTRACT

Streptococcal inhibitor of complement (SIC) is a 31-kDa extracellular protein of a few, very virulent, strains of
Streptococcus pyogenes
(particularly M1 strains). It is secreted in large quantities (about 5 mg/liter) and inhibits complement lysis by blocking the membrane insertion site on C5b67. We describe investigations into the interaction of SIC with three further major components of the innate immune system found in airway surface liquid, namely, secretory leukocyte proteinase inhibitor (SLPI), lysozyme, and lactoferrin. Enzyme-linked immunosorbent assays showed that SIC binds to SLPI and to both human and hen egg lysozyme (HEL) but not to lactoferrin. Studies using
125
I-labeled proteins showed that SIC binds approximately two molecules of SLPI and four molecules of lysozyme. SLPI binding shows little temperature dependence and a small positive enthalpy, suggesting that the binding is largely hydrophobic. By contrast, lysozyme binding shows strong temperature dependence and a substantial negative enthalpy, suggesting that the binding is largely ionic. Lysozyme is precipitated from solution by SIC. Further studies examined the ability of SIC to block the biological activities of SLPI and lysozyme. An M1 strain of group A streptococci was killed by SLPI, and the antibacterial activity of this protein was inhibited by SIC. SIC did not inhibit the antiproteinase activity of SLPI, implying that there is specific inhibition of the antibacterial domain. The antibacterial and enzymatic activities of lysozyme were also inhibited by SIC. SIC is the first biological inhibitor of the antibacterial action of SLPI to be described and may prove to be an important tool for investigating this activity in vivo. Inhibition of the antibacterial actions of SLPI and lysozyme would be advantageous to
S. pyogenes
in establishing colonization on mucosal surfaces, and we propose that this is the principal function of SIC.
Pneumococcal Infections in Humans Are Associated with Increased Apoptosis and Trafficking of Type 1 Cytokine-Producing T Cells
Authors: Kemp Kåre , Bruunsgaard Helle , Skinhøj Peter , Klarlund Pedersen Bente 
Published: October 2002

ABSTRACT

Streptococcus pneumoniae
infections are associated with considerable morbidity and mortality throughout the world. The immunopathology is characterized by an intense inflammatory reaction, including a strong acute-phase response and increased numbers of neutrophils in the circulation. However, little is known regarding the T-cell response during in vivo infections in humans. The purpose of this study was to test the hypothesis that activated T cells producing type 1 cytokines were engaged in the host response to pneumococcal infections. The phenotype and function of T cells were studied in 22 patients at admission to a department of infectious diseases and after antibiotic treatment for 1 week compared with an age-matched, healthy control group. Pneumococcal infections induced lymphopenia in the circulation due to the disappearance of activated T lymphocytes with a type 1 cytokine profile. In contrast, the numbers of naive T cells and interleukin-4-producing T cells did not change. Activated type 1 cytokine-producing cells reappeared in the circulation in relation to the treatment and clinical improvement. The underlying mechanisms during infection may include sequestration in the peripheral tissues and/or apoptosis. In fact, increased activation-induced apoptosis in the remaining peripheral lymphocytes and elevated levels of soluble Fas ligand were detected at admission to the hospital. In conclusion, these data suggest that activated T lymphocytes with a type 1 cytokine profile are highly engaged in the in vivo immune response to
S. pneumoniae
.
Nitric Oxide InhibitsCoxiella burnetiiReplication and Parasitophorous Vacuole Maturation
Authors: Howe Dale , Barrows Lorraine F. , Lindstrom Nicole M. , Heinzen Robert A. 
Published: October 2002

ABSTRACTNitric oxide is a recognized cytotoxic effector against facultative and obligate intracellular bacteria. This study examined the effect of nitric oxide produced by inducible nitric oxide synthase (iNOS) up-regulated in response to cytokine stimulation, or by a synthetic nitric oxide donor, on replication of obligately intracellularCoxiella burnetiiin murine L-929 cells. Immunoblotting and nitrite assays revealed thatC. burnetiiinfection of L-929 cells augments expression of iNOS up-regulated in response to gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Infection in the absence of cytokine stimulation did not result in demonstrable up-regulation of iNOS expression or in increased nitrite production. Nitrite production by cytokine-treated cells was significantly inhibited by the iNOS inhibitorS-methylisothiourea (SMT). Treatment of infected cells with IFN-γ and TNF-α or the synthetic nitric oxide donor 2,2′-(hydroxynitrosohydrazino)bis-ethanamine (DETA/NONOate) had a bacteriostatic effect onC. burnetiireplication. Inhibition of replication was reversed upon addition of SMT to the culture medium of cytokine-treated cells. Microscopic analysis of infected cells revealed that nitric oxide (either cytokine induced or donor derived) inhibited formation of the mature (large) parasitophorous vacuole that is characteristic ofC. burnetiiinfection of host cells. Instead, exposure of infected cells to nitric oxide resulted in the formation of multiple small, acidic vacuoles usually containing oneC. burnetiicell. Removal of nitrosative stress resulted in the coalescence of small vacuoles to form a large vacuole harboring multipleC. burnetiicells. These experiments demonstrate that nitric oxide reversibly inhibits replication ofC. burnetiiand formation of the parasitophorous vacuole.
Increased Host Resistance againstPneumocystis cariniiPneumonia in γδ T-Cell-Deficient Mice: Protective Role of Gamma Interferon and CD8+T Cells
Authors: Steele Chad , Zheng Mingquan , Young Erana , Marrero Luis , Shellito Judd E. , Kolls Jay K. 
Published: October 2002

ABSTRACTAlthough a clear relationship between αβ T-cell receptor-positive (αβ-TCR+) CD4+T cells and susceptibility toPneumocystis cariniiinfection exists, the role of other T-cell subsets is less clearly defined. Previous studies have shown that γδ-TCR+T cells infiltrate into the lung duringP. cariniipneumonia. Therefore, the present study examined the role of γδ-TCR+T cells in host defense againstP. cariniipneumonia. C57BL/6 (control) and B6.129P2-Tcrdtm1Mom(γδ-TCR+T-cell-deficient) mice were inoculated intratracheally withP. carinii. At specific time points, mice were sacrificed and analyzed forP. cariniiburden, T-cell subsets, and cytokine levels in lung tissue. Analysis ofP. cariniiburden showed a more rapid and complete resolution of infection in γδ-TCR+T-cell-deficient mice than in C57BL/6 controls. This augmented resolution was associated with elevated gamma interferon (IFN-γ) levels in bronchoalveolar lavage fluid predominantly produced by CD8+T cells, as well as an increased recruitment of CD8+T cells in general. In separate experiments, neutralization of IFN-γ or depletion of CD8+T cells early during infection abolished the augmented resolution previously observed in γδ-TCR+T-cell-deficient mice. These results show that the presence of γδ-TCR+T cells modulates host susceptibility toP. cariniipneumonia through interactions with pulmonary CD8+T cells and tissue production of IFN-γ.
Campylobacter jejunifrom Patients with Guillain-Barré Syndrome Preferentially Expresses a GD1a-Like Epitope
Authors: Nachamkin Irving , Liu Jirong , Li Ming , Ung Huong , Moran Anthony P. , Prendergast Martina M. , Sheikh Kazim 
Published: October 2002

ABSTRACTGM1- and GD1a-like ganglioside mimicry inCampylobacter jejunilipooligosaccharide (LOS) is considered to be involved in the pathogenesis ofCampylobacter-induced Guillain-Barré syndrome (GBS). Compared with gastroenteritis-related isolates, GBS-relatedC. jejuniisolates were strongly associated with the expression of GD1a-like mimicry. The presence of a few genes involved in LOS ganglioside mimicry,cst-II,cgtA, andcgtB, was also associated with GBS-related strains. GD1a-like epitope expression may be an important virulence phenotype associated with the risk of developing GBS following campylobacter infection.
Salmonella enterica
Serovar Typhimurium Periplasmic Superoxide Dismutases SodCI and SodCII Are Required for Protection against the Phagocyte Oxidative Burst
Authors: Sly Laura M. , Guiney Donald G. , Reiner Neil E. 
Published: October 2002

ABSTRACT

Vitamin D
3
(1,25-dihydroxycholecalciferol) induced the phagocyte oxidative burst and intracellular killing of
Salmonella enterica
serovar Typhimurium in a phosphatidylinositol 3-kinase-dependent manner. The antimicrobial effect was more pronounced for
Salmonella
SodCI and SodCII mutants, confirming the role of the phagocyte oxidase in the vitamin D
3
effect. The results for an in vitro system with human THP-1 cells correlate with in vivo virulence data for mice and show that both the SodCI and SodCII enzymes are required to protect against the oxidative burst.
The Human Immune Response to
Plasmodium falciparum
Includes Both Antibodies That Inhibit Merozoite Surface Protein 1 Secondary Processing and Blocking Antibodies
Authors: Nwuba Roseangela I. , Sodeinde Olugbemiro , Anumudu Chiaka I. , Omosun Yusuf O. , Odaibo Alexander B. , Holder Anthony A. , Nwagwu Mark 
Published: October 2002

ABSTRACT
Malaria merozoite surface protein 1 (MSP1) is cleaved in an essential step during erythrocyte invasion. The responses of children to natural malaria infection included antibodies that inhibit this cleavage and others that block the binding of these inhibitory antibodies. There was no correlation between the titer of the antibody to the 19-kDa fragment of MSP1 and its inhibitory activity. These findings have implications for the design of MSP1-based vaccines.
Chlamydia pneumoniae
and Hyperlipidemia Are Co-Risk Factors for Atherosclerosis: Infection Prior to Induction of Hyperlipidemia Does Not Accelerate Development of Atherosclerotic Lesions in C57BL/6J Mice
Authors: Blessing Erwin , Campbell Lee Ann , Rosenfeld Michael E. , Kuo Cho-chou 
Published: October 2002

ABSTRACT

Chlamydia pneumoniae
has been shown to accelerate atherosclerotic lesion development in hyperlipidemic animals. This study showed that
C. pneumoniae
did not accelerate lesion development in mice if a high-fat/high-cholesterol diet was started after infection, indicating that
C. pneumoniae
is a co-risk factor with hyperlipidemia for cardiovascular disease.
Yersinia
High-Pathogenicity Island Contributes to Virulence in
Escherichia coli
Causing Extraintestinal Infections
Authors: Schubert Sören , Picard Bertrand , Gouriou Stéphanie , Heesemann Jürgen , Denamur Erick 
Published: October 2002

ABSTRACT

The
Yersinia
high-pathogenicity island (HPI) encodes an iron uptake system mediated by the siderophore yersiniabactin (Ybt) and confers the virulence of highly pathogenic
Yersinia
species. This HPI is also widely distributed in human pathogenic members of the family of
Enterobacteriaceae
, above all in extraintestinal pathogenic
Escherichia coli
(ExPEC). In the present study we demonstrate a highly significant correlation of a functional HPI and extraintestinal virulence in
E. coli
. Moreover, using a mouse infection model, we show for the first time that the HPI contributes to the virulence of ExPEC.
The
N
-Acetyltransferase RimJ Responds to Environmental Stimuli To Repress
pap
Fimbrial Transcription in
Escherichia coli
Authors: White-Ziegler Christine A. , Black Alia M. , Eliades Stacie H. , Young Sarah , Porter Kimberly 
Published: October 2002

ABSTRACT

In uropathogenic
Escherichia coli
, P pili (Pap) facilitate binding to host epithelial cells and subsequent colonization. Whereas P pili can be produced at 37°C, the expression of these fimbriae is suppressed at 23°C. Previously, insertion mutations in
rimJ
, a gene encoding the N-terminal acetyltransferase of ribosomal protein S5, were shown to disrupt this thermoregulatory response, allowing
papBA
transcription at low temperature. In this study, we created an in-frame deletion of
rimJ
. This deletion relieved the repressive effects not only of low temperature but also of rich (Luria-Bertani [LB]) medium and glucose on
papBA
transcription, indicating that RimJ modulates
papBA
transcription in response to multiple environmental stimuli.
papI
transcription was also shown to be regulated by RimJ.
papBA
transcription is also controlled by a phase variation mechanism. We demonstrated that the regulators necessary to establish a phase ON state—PapI, PapB, Dam, Lrp, and cyclic AMP-CAP-are still required for
papBA
transcription in a
rimJ
mutant strain.
rimJ
mutations increase the rate at which bacteria transition into the phase ON state, indicating that RimJ inhibits the phase OFF→ON transition. A Δ
rimJ hns651
mutant is viable on LB medium but not on minimal medium. This synthetic lethality, along with transcriptional analyses, indicates that RimJ and H-NS work through separate pathways to control
papBA
transcription. Mutations in
rimJ
do not greatly influence the transcription of the
fan
,
daa
, or
fim
operon, suggesting that RimJ may be a
pap
-specific regulator. Overexpression of
rimJ
under conditions repressive for
papBA
transcription complements the Δ
rimJ
mutation but has little effect on transcription under activating conditions, indicating that the ability of RimJ to regulate transcription is environmentally controlled.
Trehalose-Mediated Inhibition of the Plasma Membrane H
+
-ATPase from
Kluyveromyces lactis
: Dependence on Viscosity and Temperature
Authors: Sampedro José G. , Muñoz-Clares Rosario A. , Uribe Salvador 
Published: October 2002

ABSTRACT

The effect of increasing trehalose concentrations on the kinetics of the plasma membrane H
+
-ATPase from
Kluyveromyces lactis
was studied at different temperatures. At 20°C, increasing concentrations of trehalose (0.2 to 0.8 M) decreased
V
max
and increased
S
0.5
(substrate concentration when initial velocity equals 0.5
V
max
), mainly at high trehalose concentrations (0.6 to 0.8 M). The quotient
V
max
/
S
0.5
decreased from 5.76 μmol of ATP mg of protein
−1
min
−1
mM
−1
in the absence of trehalose to 1.63 μmol of ATP mg of protein
−1
min
−1
mM
−1
in the presence of 0.8 M trehalose. The decrease in
V
max
was linearly dependent on solution viscosity (η), suggesting that inhibition was due to hindering of protein domain diffusional motion during catalysis and in accordance with Kramer's theory for reactions in solution. In this regard, two other viscosity-increasing agents, sucrose and glycerol, behaved similarly, exhibiting the same viscosity-enzyme inhibition correlation predicted. In the absence of trehalose, increasing the temperature up to 40°C resulted in an exponential increase in
V
max
and a decrease in enzyme cooperativity (
n
), while
S
0.5
was not modified. As temperature increased, the effect of trehalose on
V
max
decreased to become negligible at 40°C, in good correlation with the temperature-mediated decrease in viscosity. The trehalose-mediated increase in
S
0.5
was similar at all temperatures tested, and thus, trehalose effects on
V
max
/
S
0.5
were always observed. Trehalose increased the activation energy for ATP hydrolysis. Trehalose-mediated inhibition of enzymes may explain why yeast rapidly hydrolyzes trehalose when exiting heat shock.
Role of the C-Terminal Domain of the Alpha Subunit of RNA Polymerase in LuxR-Dependent Transcriptional Activation of the
lux
Operon during Quorum Sensing
Authors: Finney Angela H. , Blick Robert J. , Murakami Katsuhiko , Ishihama Akira , Stevens Ann M. 
Published: October 2002

ABSTRACT

During quorum sensing in
Vibrio fischeri
, the luminescence, or
lux
, operon is regulated in a cell density-dependent manner by the activator LuxR in the presence of an acylated homoserine lactone autoinducer molecule [
N
-(3-oxohexanoyl) homoserine lactone]. LuxR, which binds to the
lux
operon promoter at a position centered at −42.5 relative to the transcription initiation site, is thought to function as an ambidextrous activator making multiple contacts with RNA polymerase (RNAP). The specific role of the α-subunit C-terminal domain (αCTD) of RNAP in LuxR-dependent transcriptional activation of the
lux
operon promoter has been investigated. The effects of 70 alanine substitution variants of the α subunit were determined in vivo by measuring the rate of transcription of the
lux
operon via luciferase assays in recombinant
Escherichia coli
. The mutant RNAPs from strains exhibiting at least twofold-increased or -decreased activity in comparison to the wild type were further examined by in vitro assays. Since full-length LuxR has not been purified, an autoinducer-independent N-terminally truncated form of LuxR, LuxRΔN, was used for in vitro studies. Single-round transcription assays were performed using reconstituted mutant RNAPs in the presence of LuxRΔN, and 14 alanine substitutions in the αCTD were identified as having negative effects on the rate of transcription from the
lux
operon promoter. Five of these 14 α variants were also involved in the mechanisms of both LuxR- and LuxRΔN-dependent activation in vivo. The positions of these residues lie roughly within the 265 and 287 determinants in α that have been identified through studies of the cyclic AMP receptor protein and its interactions with RNAP. This suggests a model where residues 262, 265, and 296 in α play roles in DNA recognition and residues 290 and 314 play roles in α-LuxR interactions at the
lux
operon promoter during quorum sensing.
Genome-Wide Transcriptional Profiling in a Histidine Kinase Mutant of
Helicobacter pylori
Identifies Members of a Regulon
Authors: Forsyth Mark H. , Cao Ping , Garcia Preston P. , Hall Joshua D. , Cover Timothy L. 
Published: October 2002

ABSTRACT

To identify putative members of a regulon controlled by the
H. pylori
sensory histidine kinase HP0164 (HK0164), we constructed HK0164 null mutant
H. pylori
strains and analyzed bacterial gene transcription using DNA arrays. Seven genes were differentially expressed in multiple HK0164 mutant strains compared to their expression in control strains. Strain-dependent variations in differential expression were also detected. These results indicate that the signal transduction circuit utilizing HK0164 controls the transcription of at least seven genes in
H. pylori
.