bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Hyaluronic Acid Capsule of
Streptococcus uberis
Is Not Required for the Development of Infection and Clinical Mastitis
Authors: Field Terence R. , Ward Philip N. , Pedersen Lars H. , Leigh James A. 
Published: December 2002

ABSTRACT

The frequency at which the genes responsible for capsule biosynthesis occurred in field isolates of
Streptococcus uberis
was determined. Of the two genotypes detected (
hasABC
and
hasC
), the capsular genotype (
hasABC
) was more common. This genotype was present at a higher frequency in a population isolated from mastitis cases than in a population isolated from cattle bedding. The virulence of a mutant strain of
S. uberis
(TRF0-6) that lacked the ability to produce a hyaluronic acid capsule due to an insertion within its single copy of
hasA
(P. N. Ward, T. R. Field, W. G. F. Ditcham, E. Maguin, and J. A. Leigh, Infect. Immun.
69:
392-399, 2001) was compared to that of the capsular parental strain (0140J). Strains TRF0-6 and 0140J infected all mammary gland quarters following experimental challenge. The wild type and the mutant induced overt signs of disease in four out of four and in six out of eight mammary gland quarters, respectively. Both the wild type and the
hasA
mutant were resistant to killing by bovine neutrophils following cultivation in bovine milk. The ability to withstand the bactericidal action of neutrophils following growth in milk was therefore independent of the capsule and coincided with the ability of supernatants from such cultures to prevent the bactericidal action of neutrophils. This investigation revealed that, in the absence of the capsule,
S. uberis
is able to withstand the bactericidal effect of bovine neutrophils and induce mastitis in dairy cows.
Role of S-Layer Protein Antigenic Diversity in the Immune Responses of Sheep Experimentally Challenged with
Campylobacter fetus
subsp.
fetus
Authors: Grogono-Thomas R. , Blaser M. J. , Ahmadi M. , Newell D. G. 
Published: December 2002

ABSTRACT

Surface layer proteins (SLPs) are essential for induction of abortion by
Campylobacter fetus
subsp.
fetus
in experimentally challenged ewes. These proteins are encoded by multiple
sap
genes and vary in size and antigenicity. The role of SLP antigenic variation during experimental ovine infection was investigated. Following subcutaneous challenge, the SLPs were highly antigenic, and antibodies were detected in serum, milk, bile, and urine. Fecal anti-SLP antibodies were detected only in animals challenged orally. Ewes challenged with wild-type strain 23D with variable SLPs developed detectable circulating anti-SLP immunoglobulin G (IgG) antibodies by 2 weeks postchallenge. In contrast, ewes challenged with mutants of 23D that had fixed expression of a single SLP developed antibodies within 1 week postchallenge, suggesting that antigenic variation in SLPs may delay the host antibody response. Although not statistically significant, the data from challenge experiments in which vaccinated ewes were used suggested that SLP-expressing vaccines could protect animals from abortion and that this effect was independent of the SLP expressed, indicating involvement of conserved epitopes in the SLP. The conserved 184-amino-acid N-terminal region of the SLP, identified from previously published sequences, was epitope mapped with rabbit anti-SLP antisera by using overlapping synthetic 20-mer peptides. Two putative epitopes were identified at amino acids 81 to 110 and 141 to 160. Amino acids 81 to 100 also bound serum IgG antibodies from experimentally challenged sheep. Conserved antigenic regions of the SLP that induce protective immune responses may enable development of synthetic vaccine candidates for
C. fetus
subsp.
fetus
-associated ovine abortion.
Two-Component Systems in
Haemophilus influenzae
: a Regulatory Role for ArcA in Serum Resistance
Authors: De Souza-Hart J. A. , Blackstock W. , Di Modugno V. , Holland I. B. , Kok M. 
Published: December 2002

ABSTRACT

Knockout mutations were constructed in the
arcA
gene of a virulent type b strain of
Haemophilus influenzae
, and the behavior of the resulting mutants was investigated in a number of conditions that mimicked distinct steps in the natural infection pathway. In
arcA
mutants, synthesis of capsule and lipooligosaccharide (LOS) and growth in synthetic media were unaltered compared to synthesis of capsule and LOS and growth in synthetic media in the wild-type
H. influenzae
type b parent strain. However, the virulence of the
arcA
mutants for BALB/c mice was significantly reduced. Upon exposure to human blood or serum, the
arcA
mutants showed markedly reduced survival compared with the survival of its wild-type parent. Serum resistance could be fully restored by complementation in
cis
with the
H. influenzae arcA
gene but not by complementation in
cis
with the homologous gene from
Escherichia coli
. The proteomes of wild-type and mutant bacteria were markedly different, especially under anaerobic conditions, underscoring the global regulatory role of ArcAB in
H. influenzae
. Evaluation of antibody titers and classical complement activities in various serum samples pointed to complement-mediated bactericidal activity as the factor that distinguishes between the
arcA
mutant and wild-type phenotypes. Comparative analysis of the membrane fractions of the
arcA
mutants and the wild-type strain revealed several ArcA-regulated proteins, some of which may be implicated in the serum hypersensitivity phenotype.
4-1BB (CD137) Differentially Regulates Murine In Vivo Protein- and Polysaccharide-Specific Immunoglobulin Isotype Responses toStreptococcus pneumoniae
Authors: Wu Zheng-Qi , Khan Abdul Q. , Shen Yi , Wolcott Karen M. , Dawicki Wojciech , Watts Tania H. , Mittler Robert S. , Snapper Clifford M. 
Published: December 2002

ABSTRACT4-1BB (CD137) is induced on activated CD4+and CD8+T cells and delivers a costimulatory signal upon binding the 4-1BB ligand (4-1BBL) expressed on antigen-presenting cells. Induction of 4-1BB is dependent on activation via the T-cell receptor (TCR) and possibly CD28. It was previously demonstrated that both an in vivo protein (pneumococcal surface protein A [PspA])- and polysaccharide (phosphorylcholine [PC] determinant of teichoic acid)-specific immunoglobulin (Ig) isotype response toStreptococcus pneumoniaewas dependent on CD4+TCRαβ+T cells and B7-dependent costimulation through CD28. We thus postulated that 4-1BB costimulation would also play a role in regulating the in vivo anti-PspA and anti-PC response toS. pneumoniae. We demonstrate that mice genetically deficient in 4-1BBL elicit a markedly reduced IgM and IgG anti-PC but normal primary and secondary IgG anti-PspA responses toS. pneumoniaerelative to those for wild-type mice. However, injection of an agonistic anti-4-1BB monoclonal antibody (MAb), while having no significant effect on the anti-PC response, strongly inhibits the primary anti-PspA response, the generation of PspA-specific memory, and germinal center formation but does not induce a lasting state of tolerance. In contrast, anti-4-1BB MAb has no effect on the anti-PspA response when injected only at the time of secondary immunization. Delay of the addition of anti-4-1BB leads to progressively less inhibition of the primary response up to day 8. This inhibition is independent of CD8+T cells and is associated with the expansion of CD4+T cells with an activated phenotype, which is partly dependent on B7-dependent costimulation. These data are the first to suggest a stimulatory role for endogenous 4-1BB-4-1BBL interactions during a humoral immune response to a pathogen and further underscore significant differences in costimulation requirements for an in vivo protein- versus polysaccharide-specific Ig isotype response to an extracellular bacterium.
Cleavage of Antigen-Bound Immunoglobulin G by SpeB Contributes to Streptococcal Persistence in Opsonizing Blood
Authors: Eriksson Anna , Norgren Mari 
Published: December 2002

ABSTRACTGroup A streptococci (GAS) express a superantigen, SpeB, having cysteine protease activity. SpeB exhibits several properties that might contribute to virulence, the most recently discovered being the ability to cleave immunoglobulin G (IgG) in a manner similar to that of papain. In the present study, we confirmed this latter finding and found that the irreversible inhibition of SpeB protease activity completely abolishes IgG cleavage. SpeB cleavage of IgG was not species restricted since SpeB cleaved both human, rabbit, and mouse IgG. In order to investigate the nature of the SpeB cleavage of IgG, antibodies were immobilized prior to exposure to SpeB, either by unspecific binding of the Fc to GAS surface proteins or by antigen-specific binding. Analysis of the IgG molecules by SDS-PAGE showed that SpeB could cleave antigen-bound antibodies, while the IgG bound to IgG-binding proteins was protected from cleavage. In a phagocytosis assay using whole blood, the M49 GAS strain NZ131 showed a significantly higher survival than its isogenicspeBmutant. Furthermore, the addition of extracellular supernatant derived from an overnight culture of native NZ131 increased the survival of its isogenicspeBderivative. This indicates that SpeB's ability to cleave off the Fc part of antigen-bound IgG contributes to GAS escape from opsonophagocytosis while not interfering with the formation of a host-like coat by unspecific IgG binding.
Genetic Alteration of Capsule Type but Not PspA Type Affects Accessibility of Surface-Bound Complement and Surface Antigens ofStreptococcus pneumoniae
Authors: Abeyta Melanie , Hardy Gail G. , Yother Janet 
Published: December 2002

ABSTRACTTheStreptococcus pneumoniaecapsular polysaccharides and pneumococcal surface protein A (PspA) are major determinants of virulence that are antigenically variable and capable of eliciting protective immune responses. By genetically switching the pspA genes of the capsule type 2 strain D39 and the capsule type 3 strain WU2, we showed that the different abilities of antibody to PspA to protect against these strains was not related to the PspA type expressed. Similarly, the level of specific antibody binding to PspA, other surface antigens, and surface-localized C3b did not depend on the PspA type but instead was correlated with the capsule type. The type 3 strain WU2 and an isogenic derivative of D39 that expresses the type 3 capsule bound nearly identical amounts of antibody to PspA and other surface antigens, and these amounts were less than one-half the amount observed with the type 2 parent strain D39. Expression of the type 3 capsule in D39 also reduced the amount of C3b deposited and its accessibility to antibody, resulting in a level intermediate between the levels observed with WU2 and D39. Despite these effects, the capsule type was not the determining factor in anti-PspA-mediated protection, as both D39 and its derivative expressing the type 3 capsule were more resistant to protection than WU2. The specific combination of PspA and capsule type also did not determine the level of protection. The capsule structure is thus a major determinant in accessibility of surface antigens to antibody, but certain strains appear to express other factors that can influence antibody-mediated protection.
Resistance of Macrophages toMycobacterium aviumIs Induced by α2-Adrenergic Stimulation
Authors: Weatherby Kelly E. , Zwilling Bruce S. , Lafuse William P. 
Published: December 2002

ABSTRACTThe ability of macrophages to control the growth of microorganisms is increased by macrophage activation. Previously, it was shown that epinephrine activated mouse macrophages to resist the growth ofMycobacterium aviumvia α2-adrenergic stimulation. In the present study, we show that the α2-adrenergic agonist (α2-agonist) clonidine induced resistance toM. aviumgrowth in the RAW264.7 mouse macrophage cell line. The ability of catecholamines to induce resistance to mycobacteria was specific to α2-adrenergic stimulation, as α1-, β1-, and β2-agonists had no effect. Receptor signaling through Gi proteins was required. A G-protein antagonist specific for the α subunits of the Go/Gi family blocked the increased resistance induced by clonidine, while a Gs-protein antagonist was without effect. Both nitric oxide (NO) production and superoxide (O2−) production were required for the increased resistance toM. aviumgrowth induced by clonidine. Although NO production was required, clonidine did not increase the level of NO inM. avium-infected cells. Since NO and O2−interact to produce peroxynitrite (ONOO−), we examined whether ONOO−mediates the increased resistance toM. aviuminduced by clonidine. 5,10,15,20-Tetrakis(4-sulfonatophenyl)prophyrinato iron (III) chloride (FeTPPS), a specific scavenger of ONOO−, inhibited the effect of clonidine onM. aviumgrowth. Clonidine also increased the production of ONOO−inM. avium-infected RAW264.7 cells, as measured by the oxidation of 123-dihydrorhodamine and the production of nitrated tyrosine residues. We therefore conclude that α2-adrenergic stimulation activates macrophages to resist the growth ofM. aviumby enhancing the production of ONOO−.
Induction of Osteoclastogenesis and Matrix Metalloproteinase Expression by the Lipooligosaccharide ofTreponema denticola
Authors: Choi Bong-Kyu , Lee Hyun Jung , Kang Jung Hwa , Jeong Gook Jin , Min Cheon Ki , Yoo Yun-Jung 
Published: December 2002

ABSTRACTAlveolar bone destruction is a characteristic feature of periodontitis.Treponema denticolais known to be involved in periodontitis. To elucidate the role ofT. denticolain alveolar bone destruction in periodontitis, the effects of lipooligosaccharide (LOS) fromT. denticolaon osteoclast formation and on expression of osteoclast differentiation factor (ODF) and osteoprotegerin (OPG) mRNAs were examined in a coculture system by using mouse calvaria and bone marrow cells. In addition, the effect ofT. denticolaLOS on expression of matrix metalloproteinases (MMPs), which are involved in bone resorption, was estimated in mouse calvaria-derived osteoblastic cells. When the mouse calvaria and bone marrow cells were challenged with LOS (0.1 to 10 μg/ml) for 4 days, the number of tartrate-resistant acid phosphatase-positive multinucleated cells increased in a dose-dependent manner. The expression of ODF mRNA increased, while OPG mRNA expression decreased. Polymyxin B changed the effect of LOS (10 μg/ml) on ODF and OPG mRNA expression to the control level. LOS (10 μg/ml) stimulated prostaglandin E2(PGE2) production in the cocultures. Adding indomethacin, an inhibitor of prostaglandin synthesis, resulted in a reduction in the number of osteoclasts induced by LOS and eliminated the effect ofT. denticolaLOS on ODF and OPG mRNA expression.T. denticolaLOS increased the levels of mRNAs encoding MMP-3, -8, -9, -10, -13, and -14. Expression of one of these mRNAs, MMP-9 mRNA, was significantly induced byT. denticolaLOS. These findings suggest that LOS fromT. denticolastimulates osteoclastogenesis and MMP expression. Up-regulation of ODF and down-regulation of OPG by a PGE2-dependent mechanism were involved in the osteoclastogenesis induced byT. denticolaLOS.
Seeligeriolysin O, a Cholesterol-Dependent Cytolysin ofListeria seeligeri, Induces Gamma Interferon from Spleen Cells of Mice
Authors: Ito Yutaka , Kawamura Ikuo , Kohda Chikara , Baba Hisashi , Nomura Takamasa , Kimoto Terumi , Watanabe Isao , Mitsuyama Masao 
Published: December 2002

ABSTRACTSeeligeriolysin O (LSO), one of the cholesterol-dependent cytolysins produced byListeria seeligeri, shows 80% homology to listeriolysin O (LLO) produced byListeria monocytogenesat the amino acid sequence level. In addition to cytolytic activity, LLO has been shown to exhibit cytokine-inducing activity. In order to determine whether LSO is also capable of exhibiting these two different activities, we constructed a recombinant full-length LSO (rLSO530) and a noncytolytic truncated derivative with a C-terminal deletion (rLSO483) and compared these molecules with recombinant LLO. The cytolytic rLSO530 molecule could induce gamma interferon (IFN-γ) production in spleen cells when the cytolytic activity was blocked by treatment with cholesterol. The noncytolytic truncated rLSO483 molecule also induced IFN-γ production. Anti-LLO polyclonal antibody inhibited not only LLO-induced IFN-γ production but also LSO-induced IFN-γ production. Both NK cells and CD11b+cells were required for LSO-induced IFN-γ production. Among the various cytokines expressed in CD11b+cells, interleukin-12 (IL-12) and IL-18 appeared to be essential. We concluded that LSO exhibits the same biological activity as LLO.
Placental Tumor Necrosis Factor Alpha but Not Gamma Interferon Is Associated with Placental Malaria and Low Birth Weight in Malawian Women
Authors: Rogerson Stephen J. , Brown Heidi C. , Pollina Elena , Abrams Elizabeth T. , Tadesse Eyob , Lema Valentino M. , Molyneux Malcolm E. 
Published: December 2002

ABSTRACTMalaria in pregnancy predisposes to maternal anemia and low birth weight (LBW). We examined the possible roles of the cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) in these adverse outcomes. We measured cytokine concentrations in placental, peripheral, and cord blood plasma in relation to malaria parasitemia and placental monocyte accumulation in 276 Malawian women. Maternal hemoglobin concentration, human immunodeficiency virus status, and infant birth weight were determined. Concentrations of TNF-α in placental blood were correlated with densities ofPlasmodium falciparum-infected erythrocytes (P< 0.0001) and of intervillous monocyte infiltrates (P< 0.0001) on placental histology. Peripheral blood TNF-α concentrations were relatively low and were weakly associated with malaria. TNF-α concentrations were higher in placental blood, where they were strongly associated with malaria. Placental plasma TNF-α levels were higher in women who had LBW babies (P= 0.0027), women with febrile symptoms (P< 0.0001), and teenage mothers (P= 0.04) than in other women. The presence of TNF-α in cord blood was not associated with malaria infection. IFN-γ levels were infrequently elevated, and elevated IFN-γ levels were not associated with poor pregnancy outcomes. Placental production of TNF-α, but not of IFN-γ, may be implicated in impaired fetal growth in Malawian women.
Age-Related Disparity in Functional Activities of Human Group C Serum Anticapsular Antibodies Elicited by Meningococcal Polysaccharide Vaccine
Authors: Harris Shannon L. , King W. James , Ferris Wendy , Granoff Dan M. 
Published: December 2002

ABSTRACTSerum bactericidal activity confers protection against meningococcal disease, but it is not known whether vaccine-induced anticapsular antibodies that lack bactericidal activity are protective. We developed an infant rat challenge model using a naturally occurring O-acetylated strain ofNeisseria meningitidisgroup C and a strain that was negative for O acetylation (OAc). Rats 4 to 7 days of age inoculated intraperitoneally (i.p.) with ∼103CFU of either strain developed >5 × 105CFU/ml of blood obtained 18 h later. Dilutions of preimmunization sera given i.p. 2 h before the bacterial challenge had no effect on bacteremia, whereas group C anticapsular antibody in sera from adults immunized with meningococcal polysaccharide vaccine conferred complete or partial (>99% decrease in CFU per milliliter of blood) protection against the OAc-positive or OAc-negative strain, respectively, at antibody doses as low as 0.04 μg/rat. Anticapsular antibody at doses fivefold higher (0.18 to 0.2 μg/rat) in pooled sera from children immunized at a mean age of 2.6 years failed to protect rats, but antibody at the same or fivefold-lower dose in a serum pool from a group of children immunized at 4 years of age gave complete or partial protection. Protective activity was observed with some serum pools that lacked detectable complement-mediated bactericidal activity (titers < 1:4) and correlated with increasing antibody avidity. Thus, not only does the magnitude of the group C antibody response to meningococcal polysaccharide vaccine increase with increasing age but there are also age-related affects on antibody functional activity such that higher serum concentrations of vaccine-induced antibody are required for protection of immunized children than for immunized adults.
Impact of Vector Priming on the Immunogenicity of RecombinantSalmonellaVaccines
Authors: Vindurampulle Christofer J. , Attridge Stephen R. 
Published: December 2002

ABSTRACTThere are conflicting reports concerning the impact of prior vector priming on the immunogenicity of recombinant-Salmonella-based vaccines. A comparison of experimental protocols identified two variables which might account for this inconsistency: the potential of the vector strain to colonize the murine gut-associated lymphoid tissue (GALT) and the nature of the foreign antigen subsequently delivered by the recombinantSalmonellaconstruct. The former was investigated by constructing anaroAmutant of theSalmonella entericaserovar Stanley vector previously used in our laboratory. Although the introduction of anaroAmutation had surprisingly little effect on GALT colonization, it did reduce the strength of antilipopolysaccharide (anti-LPS) antibody responses and the impact of vector priming. Studies were also performed to ascertain the extent to which any observed hyporesponsiveness consequent upon vector priming might be determined by the characteristics of the foreign antigen.S. entericaserovar Stanley was used to deliver either of twoEscherichia coliantigens, K88 pilus protein or the LT-B toxin subunit, to vector-primed mice. Both serum immunoglobulin G (IgG) and intestinal IgA responses to K88 were completely abolished, and those to LT-B were significantly reduced, as a consequence of vector priming. When similar experiments were performed with anaroA S. entericaserovar Dublin vector, responses to K88 were significantly reduced but those to LT-B were unaffected by vector priming. Paradoxically, a priming infection with this vector induced stronger anti-LPS antibody responses but was less likely to elicit a state of hyporesponsiveness to subsequently presented foreign antigen. The impact of vector priming thus depends on both theSalmonellastrain used and the nature of the foreign antigen, but our present data strengthen concerns that preexisting antivector immunity represents a serious threat to theSalmonella-based vaccine strategy.