bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paucibacillary Tuberculosis in Mice after Prior Aerosol Immunization with
Mycobacterium bovis
BCG
Authors: Nuermberger E. L. , Yoshimatsu T. , Tyagi S. , Bishai W. R. , Grosset J. H. 
Published: January 2004

ABSTRACT

To develop a murine model of paucibacillary tuberculosis for experimental chemotherapy of latent tuberculosis infection, mice were immunized with viable
Mycobacterium bovis
BCG by the aerosol or intravenous route and then challenged six weeks later with virulent
Mycobacterium tuberculosis
. The day after immunization, the counts were 3.71 ± 0.10 log
10
CFU in the lungs of aerosol-immunized mice and 3.65 ± 0.11 and 4.93 ± 0.07 log
10
CFU in the lungs and spleens of intravenously immunized mice, respectively. Six weeks later, the lungs of all BCG-immunized mice had many gross lung lesions and splenomegaly; the counts were 5.97 ± 0.14 and 3.54 ± 0.07 log
10
CFU in the lungs and spleens of aerosol-immunized mice, respectively, and 4.36 ± 0.28 and 5.12 ± 0.23 log
10
CFU in the lungs and spleens of intravenously immunized mice, respectively. Mice were then aerosol challenged with
M. tuberculosis
by implanting 2.37 ± 0.13 log
10
CFU in the lungs. Six weeks after challenge,
M. tuberculosis
had multiplied so that the counts were 6.41 ± 0.27 and 4.44 ± 0.14 log
10
CFU in the lungs and spleens of control mice, respectively. Multiplication of
M. tuberculosis
was greatly limited in BCG-immunized mice. Six weeks after challenge, the counts were 4.76 ± 0.24 and 3.73 ± 0.34 log
10
CFU in the lungs of intravenously immunized and aerosol-immunized mice, respectively. In contrast to intravenously immunized mice, there was no detectable dissemination to the spleen in aerosol-immunized mice. Therefore, immunization of mice with BCG by the aerosol route prior to challenge with a low dose of
M. tuberculosis
resulted in improved containment of infection and a stable paucibacillary infection. This model may prove to be useful for evaluation of new treatments for latent tuberculosis infection in humans.
New Aspects Regarding Evolution and Virulence of
Listeria monocytogenes
Revealed by Comparative Genomics and DNA Arrays
Authors: Doumith Michel , Cazalet Christel , Simoes Natalie , Frangeul Lionel , Jacquet Christine , Kunst Frank , Martin Paul , Cossart Pascale , Glaser Philippe , Buchrieser Carmen 
Published: January 2004

ABSTRACT

Listeria monocytogenes
is a food-borne bacterial pathogen that causes a wide spectrum of diseases, such as meningitis, septicemia, abortion, and gastroenteritis, in humans and animals. Among the 13
L. monocytogenes
serovars described, invasive disease is mostly associated with serovar 4b strains. To investigate the genetic diversity of
L. monocytogenes
strains with different virulence potentials, we partially sequenced an epidemic serovar 4b strain and compared it with the complete sequence of the nonepidemic
L. monocytogenes
EGDe serovar 1/2a strain. We identified an unexpected genetic divergence between the two strains, as about 8% of the sequences were serovar 4b specific. These sequences included seven genes coding for surface proteins, two of which belong to the internalin family, and three genes coding for transcriptional regulators, all of which might be important in different steps of the infectious process. Based on the sequence information, we then characterized the gene content of 113
Listeria
strains by using a newly designed
Listeria
array containing the “flexible” part of the sequenced
Listeria
genomes. Hybridization results showed that all of the previously identified virulence factors of
L. monocytogenes
were present in the 93
L. monocytogenes
strains tested. However, distinct patterns of the presence or absence of other genes were identified among the different
L. monocytogenes
serovars and
Listeria
species. These results allow new insights into the evolution of
L. monocytogenes
, suggesting that early divergence of the ancestral
L. monocytogenes
serovar 1/2c strains from the serovar 1/2b strains led to two major phylogenetic lineages, one of them including the serogroup 4 strains, which branched off the serovar 1/2b ancestral lineage, leading (mostly by gene loss) to the species
Listeria innocua
. The identification of 30
L. monocytogenes
-specific and several serovar-specific marker genes, such as three
L. monocytogenes
serovar 4b-specific surface protein-coding genes, should prove powerful for the rapid tracing of listeriosis outbreaks, but it also represents a fundamental basis for the functional study of virulence differences between
L. monocytogenes
strains.
Molecular Characterization of a Glucose-Inhibited Division Gene,
gidA
, That Regulates Cytotoxic Enterotoxin of
Aeromonas hydrophila
Authors: Sha Jian , Kozlova E. V. , Fadl A. A. , Olano J. P. , Houston C. W. , Peterson J. W. , Chopra A. K. 
Published: January 2004

ABSTRACT

By using a mini-transposon, we obtained two mutated strains of a diarrheal isolate, SSU, of
Aeromonas hydrophila
that exhibited a 50 to 53% reduction in the hemolytic activity and 83 to 87% less cytotoxic activity associated with the cytotoxic enterotoxin (Act). Act is a potent virulence factor of
A. hydrophila
and has been shown to contribute significantly to the development of both diarrhea and septicemia in animal models. Subsequent cloning and DNA sequence analysis revealed that transposon insertion occurred at different locations in these two mutants within the same 1,890-bp open reading frame for the glucose-inhibited division gene (
gidA
). A similar reduction in hemolytic (46%) and cytotoxic (81%) activity of Act was noted in the
gidA
isogenic mutant of
A. hydrophila
that was generated by marker exchange mutagenesis. Northern blot analysis revealed that the transcription of the cytotoxic enterotoxin gene (
act
) was not altered in the
gidA
transposon and isogenic mutants. However, by generating a chromosomal
act
::alkaline phosphatase gene (
phoA
) reporter construct, we demonstrated significantly reduced phosphatase activity in these mutants, indicating the effect of glucose-inhibited division (GidA) protein in modulating
act
gene expression at the translational level. The biological effects of Act in the
gidA
mutants were restored by complementation. The virulence of the
gidA
mutants in mice was dramatically reduced compared to the those of the wild-type (WT) and complemented strains of
A. hydrophila
. The histopathological examination of lungs, in particular, indicated severe congestion, alveolar hemorrhage, and acute inflammatory infiltrate in the interstitial compartment and the alveolar spaces when mice were infected with the WT and complemented strains. Minimal-to-mild changes were noted in the lungs with the
gidA
mutants. Taken together, our data indicate for the first time that GidA regulates the most-potent virulence factor of
A. hydrophila
, Act.
Conservation ofBabesia bovisSmall Heat Shock Protein (Hsp20) among Strains and Definition of T Helper Cell Epitopes Recognized by Cattle with Diverse Major Histocompatibility Complex Class II Haplotypes
Authors: Norimine Junzo , Mosqueda Juan , Palmer Guy H. , Lewin Harris A. , Brown Wendy C. 
Published: January 2004

ABSTRACTBabesia bovissmall heat shock protein (Hsp20) is recognized by CD4+T lymphocytes from cattle that have recovered from infection and are immune to challenge. This candidate vaccine antigen is related to a protective antigen ofToxoplasma gondii, Hsp30/bag1, and both are members of the α-crystallin family of proteins that can serve as molecular chaperones. In the present study, immunofluorescence microscopy determined that Hsp20 is expressed intracellularly in all merozoites. Importantly, Hsp20 is also expressed by tick larval stages, including sporozoites, so that natural tick-transmitted infection could boost a vaccine-induced response. The predicted amino acid sequence of Hsp20 from merozoites is completely conserved among differentB. bovisstrains. To define the location of CD4+T-cell epitopes for inclusion in a multiepitope peptide or minigene vaccine construct, truncated recombinant Hsp20 proteins and overlapping peptides were tested for their ability to stimulate T cells from immune cattle. Both amino-terminal (amino acids [aa] 1 to 105) and carboxy-terminal (aa 48 to 177) regions were immunogenic for the majority of cattle in the study, stimulating strong proliferation and IFN-γ production. T-cell lines from all individuals with distinctDRB3haplotypes responded to aa 11 to 62 of Hsp20, which contained one or more immunodominant epitopes for each animal. One epitope, DEQTGLPIKS (aa 17 to 26), was identified by T-cell clones. The presence of strain-conserved T helper cell epitopes in aa 11 to 62 of the ubiquitously expressed Hsp20 that are presented by major histocompatibility complex class II molecules represented broadly in the Holstein breed supports the inclusion of this region in vaccine constructs to be tested in cattle.
Protection against CD95-Induced Apoptosis by Chlamydial Infection at a Mitochondrial Step
Authors: Fischer Silke F. , Harlander Thomas , Vier Juliane , Häcker Georg 
Published: January 2004

ABSTRACTChlamydiae are obligate intracellular bacteria that infect human epithelial and myeloid cells. Previous work has established that chlamydiae are able to protect a cell against apoptosis induced by certain experimentally applied stimuli. Here we provide an analysis of this protective activity against the signal transduction during CD95-induced apoptosis. In HeLa cells overexpressing CD95, infection withChlamydia trachomatisinhibited the appearance of apoptotic morphology, effector caspase activity, the activation of caspase-9 and -3, and the release of cytochromecfrom mitochondria. However, caspase-8-processing and activity (measured as cleavage of Bid) were unaffected by the chlamydial infection. Similarly, infection with the speciesC. pneumoniaedid not prevent the activation of caspase-8 but inhibited the appearance of effector caspase activity upon signaling through CD95. Furthermore, infection withC. trachomatiswas able to inhibit CD95-induced apoptosis in Jurkat lymphoid cells, where a mitochondrial contribution is required, but not in SKW6.4 lymphoid cells, where caspase-8 directly activates caspase-3. Taken together, these data show that chlamydial infection can protect cells against CD95-induced apoptosis but only where a mitochondrial signaling step is necessary for apoptotic signal transduction.
Gastroenteritis in NF-κB-Deficient Mice Is Produced with Wild-TypeCamplyobacter jejunibut Not withC. jejuniLacking Cytolethal Distending Toxin despite Persistent Colonization with Both Strains
Authors: Fox James G. , Rogers Arlin B. , Whary Mark T. , Ge Zhongming , Taylor Nancy S. , Xu Sandy , Horwitz Bruce H. , Erdman Susan E. 
Published: January 2004

ABSTRACTCampylobacter jejunicontinues to be a leading cause of bacterial enteritis in humans. However, because there are no readily available animal models to study the pathogenesis ofC. jejuni-related diseases, the significance of potential virulence factors, such as cytolethal distending toxin (CDT), in vivo are poorly understood. Mice deficient in NF-κB subunits (p50−/−p65+/−) in a C57BL/129 background are particularly susceptible to colitis induced by another enterohepatic microaerobe,Helicobacter hepaticus, which, likeC. jejuni, produces CDT. Wild-typeC. jejuni81-176 and an isogenic mutant lacking CDT activity (cdtBmutant) were inoculated into NF-κB-deficient (3X) and C57BL/129 mice. Wild-typeC. jejunicolonized 29 and 50% of the C57BL/129 mice at 2 and 4 months postinfection (p.i.), respectively, whereas theC. jejuni cdtBmutant colonized 50% of the C57BL/129 mice at 2 p.i. but none of the mice at 4 months p.i. Although the C57BL/129 mice developed mild gastritis and typhlocolitis, they had robust immunoglobulin G (IgG) and Th1-promoted IgG2a humoral responses to both the wild-type strain and theC. jejuni cdtBmutant. In contrast, 75 to 100% of the 3X mice were colonized with both the wild type and theC. jejuni cdtBmutant at similar levels at all times examined. Wild-typeC. jejunicaused moderately severe gastritis and proximal duodenitis in 3X mice that were more severe than the gastrointestinal lesions caused by theC. jejuni cdtBmutant. Persistent colonization of NF-κB-deficient mice with the wild type and theC. jejuni cdtBmutant was associated with significantly impaired IgG and IgG2a humoral responses (P< 0.001), which is consistent with an innate or adaptive immune system defect(s). These results suggest that the mechanism of clearance ofC. jejuniis NF-κB dependent and that CDT may have proinflammatory activity in vivo, as well as a potential role in the ability ofC. jejunito escape immune surveillance. NF-κB-deficient mice should be a useful model to further study the role of CDT and other aspects ofC. jejunipathogenesis.
Antibodies to Malaria Peptide Mimics Inhibit
Plasmodium falciparum
Invasion of Erythrocytes
Authors: Casey Joanne L. , Coley Andrew M. , Anders Robin F. , Murphy Vince J. , Humberstone Karen S. , Thomas Alan W. , Foley Michael 
Published: January 2004

ABSTRACT

Apical membrane antigen 1 (AMA1) is expressed on the surfaces of
Plasmodium falciparum
merozoites and is thought to play an important role in the invasion of erythrocytes by malaria parasites. To select for peptides that mimic conformational B-cell epitopes on AMA1, we screened a phage display library of >10
8
individual peptides for peptides bound by a monoclonal anti-AMA1 antibody, 4G2dc1, known to inhibit
P. falciparum
invasion of erythrocytes. The most reactive peptides, J1, J3, and J7, elicited antibody responses in rabbits that recognized the peptide immunogen and both recombinant and parasite AMA1. Human antibodies in plasma samples from individuals exposed to chronic malaria reacted with J1 and J7 peptides and were isolated using immobilized peptide immunoadsorbents. Both rabbit and human antibodies specific for J1 and J7 peptides were able to inhibit the invasion of erythrocytes by
P. falciparum
merozoites. This is the first example of phage-derived peptides that mimic an important epitope of a blood-stage malaria vaccine candidate, inducing and isolating functional protective antibodies. Our data support the use of J1 and J7 peptide mimics as in vitro correlates of protective immunity in future AMA1 vaccine trials.
Platelet-Activating Factor Receptor Deficiency Delays Elimination of Adult Worms but Reduces Fecundity inStrongyloides venezuelensis-Infected Mice
Authors: Negrão-Corrêa Deborah , Souza Danielle G. , Pinho Vanessa , Barsante Michele M. , Souza Adriano L. S. , Teixeira Mauro M. 
Published: January 2004

ABSTRACTWe describe the parasitological kinetics and histopathological and immunological alterations in platelet-activating factor receptor-deficient (PAFR−/−) and wild-type mice after a singleStrongyloides venezuelensisinfection (subcutaneous inoculation of 500 L3 larvae). There was no difference in the numbers of worms that reached and became established in the small intestines of PAFR−/−and wild-type mice. However, at 12 days after infection, significantly more worms were recovered from PAFR−/−mice. Although PAFR−/−infected mice showed a delay in elimination of adult worms, worms established in the small intestine of these mice produced a significantly lower number of eggs due to a reduction in worm fecundity. There were also significant reductions in the number of circulating and tissue eosinophils and tumor necrosis factor levels in the small intestines of PAFR−/−mice infected for 7 days compared to the number and level in wild-type mice. Histological analysis confirmed the reduced inflammatory process and revealed that the PAFR−/−mice had a smaller number of goblet cells. The concentrations of the type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-10 were lower in small intestine homogenates and in supernatants of antigen-stimulated lymphocytes from spleens or mesenteric lymph nodes of PAFR−/−mice than in the corresponding preparations from wild-type mice. Thus, inS. venezuelensis-infected PAFR−/−mice, decreased intestinal inflammation is associated with enhanced worm survival but decreased fecundity. We suggest that although a Th2-predominant inflammatory response decreases worm survival, the worm may use factors produced during this response to facilitate egg output and reproduction. PAFR-mediated responses appear to modulate these host-derived signals that are important for worm fecundity.
Haemophilus ducreyi
Strain ATCC 27722 Contains a Genetic Element with Homology to the
Vibrio
RS1 Element That Can Replicate as a Plasmid and Confer NAD Independence on
Haemophilus influenzae
Authors: Munson Robert S. , Zhong Huachun , Mungur Rachna , Ray William C. , Shea Robin J. , Mahairas Gregory G. , Mulks Martha H. 
Published: January 2004

ABSTRACT

The nucleotide sequence of pNAD1, a plasmid from
Haemophilus ducreyi
identified on the basis of its ability to confer NAD independence on
Actinobacillus pleuropneumoniae
and
H. influenzae
, has been determined. In addition to containing the
nadV
gene, the plasmid contains homologues of the
rstR
and
rstA
genes, genes encoding repressor and replication proteins, respectively, in the
Vibrio
CTXφ and the
Vibrio
RS1 element, suggesting a single-stranded bacteriophage origin for pNAD1. Tandem copies of the plasmid are integrated into the
H. ducreyi
35000HP genome.
Rapid Accumulation of Eosinophils in Lung Lesions in Guinea Pigs Infected with
Mycobacterium tuberculosis
Authors: Lasco Todd M. , Turner Oliver C. , Cassone Lynne , Sugawara Isamu , Yamada Hiroyuki , McMurray David N. , Orme Ian M. 
Published: January 2004

ABSTRACT

Guinea pig eosinophils were positively identified in bronchoalveolar lavage populations and in the lung granulomas of
Mycobacterium tuberculosis
-infected guinea pigs. It is possible that the rapid influx of these cells, and their subsequent degranulation during acute pulmonary tuberculosis, may play a key role in the susceptibility of this animal model.
Type III Secretion: a Virulence Factor Delivery System Essential for the Pathogenicity of
Burkholderia mallei
Authors: Ulrich Ricky L. , DeShazer David 
Published: January 2004

ABSTRACT

By creating mutations in the
Burkholderia mallei
ATCC 23344 animal pathogen-like type III secretion system (TTSS), this study analyzes the correlation between type III secretion and the pathogenicity of ATCC 23344 in vivo. Mutagenesis demonstrated that a functional TTSS was required for the full pathogenicity of ATCC 23344 in the BALB/c mouse and Syrian hamster models of infection. However, vaccination with each mutant failed to elicit a protective immunity against challenge with wild-type ATCC 23344.
Heat Shock Protein 60 Is the Major Antigen Which Stimulates Delayed-Type Hypersensitivity Reaction in the Macaque Model ofChlamydia trachomatisSalpingitis
Authors: Lichtenwalner Anne B. , Patton Dorothy L. , Van Voorhis Wesley C. , Sweeney Yvonne T. Cosgrove , Kuo Cho-Chou 
Published: January 2004

ABSTRACTChlamydial delayed-type hypersensitivity antigens were analyzed by using the subcutaneous salpingeal autotransplant model ofMacaca nemestrinainfected withChlamydia trachomatisserovar E. Heat shock protein 60 was the only antigen shown to induce delayed-type hypersensitivity among other antigens tested, including UV-inactivated organisms, recombinant major outer membrane protein, purified outer membrane proteins, and heat shock protein 10.
Evidence for Acquisition of the Lipooligosaccharide Biosynthesis Locus inCampylobacter jejuniGB11, a Strain Isolated from a Patient with Guillain-Barré Syndrome, by Horizontal Exchange
Authors: Gilbert Michel , Godschalk Peggy C. R. , Karwaski Marie-France , Ang C. Wim , van Belkum Alex , Li Jianjun , Wakarchuk Warren W. , Endtz Hubert P. 
Published: January 2004

ABSTRACTCampylobacter jejuniGB11, a strain isolated from a patient with Guillain-Barré syndrome, has been shown to be genetically closely related to the completely sequenced strainC. jejuniNCTC 11168 by various molecular typing and serotyping methods. However, we observed that the lipooligosaccharide (LOS) biosynthesis genes strongly diverged between GB11 and NCTC 11168. We sequenced the LOS biosynthesis locus of GB11 and found that it was nearly identical to the class A LOS locus from theC. jejuniHS:19 Penner serotype strain (ATCC 43446). Analysis of the DNA sequencing data showed that a horizontal exchange event involving at least 14.26 kb had occurred in the LOS biosynthesis locus of GB11 betweengalE(Cj1131c in NCTC 11168) andgmhA(Cj1149 in NCTC 11168). Mass spectrometry of the GB11 LOS showed that GB11 expressed an LOS outer core that mimicked the carbohydrate portion of the gangliosides GM1a and GD1a, similar toC. jejuniATCC 43446. The serum from the GB11-infected patient was shown to react with the LOS from both GB11 and ATCC 43446 but not with that from NCTC 11168. These data indicate that the antiganglioside response in the GB11-infected patient was raised against the structures synthesized by the acquired class A LOS locus.
Periodontitis Vaccine Decreases Local Prostaglandin E
2
Levels in a Primate Model
Authors: Roberts Frank A. , Houston Laura S. , Lukehart Sheila A. , Mancl Lloyd A. , Persson G. Rutger , Page Roy C. 
Published: January 2004

ABSTRACT

Interleukin-1β, tumor necrosis factor alpha, prostaglandin E
2
(PGE
2
), and
Porphyromonas gingivalis-
specific immunoglobulin G levels in gingival crevicular fluid were measured in primates immunized with a
P. gingivalis
vaccine followed by ligature-induced periodontitis. Only PGE
2
levels were dramatically suppressed (
P
< 0.0001) in immunized animals versus controls. A significant correlation (
P
< 0.027) was also found between PGE
2
levels and decreased bone loss scores. This study presents the first evidence of a potential mechanism involved in periodontitis vaccine-induced suppression of bone loss in a nonhuman primate model and offers insight into the role of PGE
2
in periodontal destruction.
Activated THP-1 Cells: an Attractive Model for the Assessment of Intracellular Growth Rates ofMycobacterium tuberculosisIsolates
Authors: Theus S. A. , Cave M. D. , Eisenach K. D. 
Published: January 2004

ABSTRACTCapacity of certainMycobacterium tuberculosisisolates to grow more rapidly in human macrophages may be indicative of increased virulence. Significant differences were observed in intracellular growth of two isolates from sites of tuberculosis transmission, with an outbreak-associated strain growing faster than a strain causing disease in only one person. Activated THP-1 cells are a suitable alternative to peripheral blood monocyte models.
An
msbB
Homologue Carried in Plasmid pO157 Encodes an Acyltransferase Involved in Lipid A Biosynthesis in
Escherichia coli
O157:H7
Authors: Kim Sang-Hyun , Jia Wenyi , Bishop Russell E. , Gyles Carlton 
Published: January 2004

ABSTRACT

Escherichia coli
O157:H7 carries a chromosomal
msbB1
and a plasmid-encoded
msbB2
gene. We characterized
msbB2
function as a homologue of
msbB1
by examination of wild-type organisms and mutant strains that lacked functional
msbB1
,
msbB2
, and both
msbB1
and
msbB2.
The
msbB
double-mutant strain generated pentaacyl lipid A, while the single-mutant strains synthesized hexaacyl lipid A. Complementation with overexpressed
msbB2
converted pentaacyl into hexaacyl lipid A in the double-mutant strain. The transcription of both
msbB
genes occurred simultaneously. Lack of MsbB2 activity slightly increased the microheterogeneity of the lipid A species. These results suggest that the
msbB2
gene plays a role not only in the routine generation of fully hexaacylated lipid A but also in suppressing the microheterogeneity of lipid A species, the endotoxic determinant of the organism.
Needle-Free Skin Patch Vaccination Method for Anthrax
Authors: Matyas Gary R. , Friedlander Arthur M. , Glenn Gregory M. , Little Stephen , Yu Jianmei , Alving Carl R. 
Published: January 2004

ABSTRACT
Three immunizations of mice with recombinant protective antigen (rPA) by transcutaneous immunization (TCI) induced long-term neutralizing antibody titers that were superior to those obtained with aluminum-adsorbed rPA. In addition, rPA alone exhibited adjuvant activity for TCI. Forty-six weeks after completion of TCI, 100% protection was observed against lethal anthrax challenge.