bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disparate Findings on the Role of Virulence Factors of
Enterococcus faecalis
in Mouse and Rat Models of Peritonitis
Authors: Dupont Herve , Montravers Philippe , Mohler Jacqueline , Carbon Claude 
Published: December 2019

ABSTRACT

The role of
Enterococcus faecalis
in polymicrobial peritonitis is still debated. Virulence factors expressed in some enterococcal strains might be involved in the pathogenicity of these organisms. To clarify their role, three of these virulence factors (cytolysin, gelatinase, and aggregation substance) were studied in six isogenic strains of
E. faecalis
expressing various combinations of these factors. Since the pathogenic effects of enterococci are only moderate, the expression of their virulence might vary from one animal species to another and from one type of infection to another. Therefore, we evaluated these effects in two animal models, i.e., a systemic infection in mice in which we assessed the virulence of the strains in 50% lethal dose studies and a model of compartmentalized infection in rats in which the microbiologic and inflammatory effects of the strains were evaluated in monomicrobial or polymicrobial infection. In mice, significant differences were observed in the cumulative survival curves depending on the virulence factors (
P
< 0.0001 [log rank test]). In rats, monomicrobial infection induced only mild changes. In polymicrobial peritonitis, the virulence factors mainly increased the inflammatory response while the changes observed in the microbiologic response were minimal. The combination of two virulence factors did not significantly increase the severity of infection either in the mice model or the polymicrobial rat model. These data argue for species and model dependence of the role of the virulence factors studied here and suggest that other important factors may be involved in the pathogenicity of enterococci.
Volatile Fatty Acid, Metabolic By-Product of Periodontopathic Bacteria, Induces Apoptosis in WEHI 231 and RAJI B Lymphoma Cells and Splenic B Cells
Authors: Kurita-Ochiai Tomoko , Ochiai Kuniyasu , Fukushima Kazuo 
Published: December 2019

ABSTRACTThe ability of butyric acid, an extracellular metabolite from periodontopathic bacteria, to induce apoptosis in murine WEHI 231 cells, splenic B cells, and human RAJI cells was examined. The culture filtrate ofPorphyromonas gingivalis,Prevotella loescheii, andFusobacterium nucleatum, which contains high a percentage of butyric acid, induced DNA fragmentation in WEHI 231 cells. Volatile fatty acid, especially butyric acid, significantly suppressed B-cell viability in a concentration-dependent fashion. The DNA fragmentation assay indicated that butyric acid rapidly induced apoptosis in WEHI 231 cells (with 1.25 mM butyric acid and 6 h after treatment), splenic B cells (with 1.25 mM butyric acid), and RAJI cells (with 2.5 mM butyric acid). Incubation of WEHI 231 cells with butyric acid for 16 h resulted in the typical ladder pattern of DNA fragmentation and the apoptoic change such as chromatin condensation and hypodiploid nuclei. Cell cycle analysis implied that butyric acid arrested the cells at the G1phase. The inhibitory assay suggested that butyric acid-induced apoptosis of WEHI 231 and splenic B cells was inhibited by W-7, a calmodulin inhibitor. These results suggest that calmodulin-dependent regulation is involved in the signal transduction pathway of butyric acid.
Mutacin Production by
Streptococcus mutans
May Promote Transmission of Bacteria from Mother to Child
Authors: Grönroos L. , Saarela M. , Mättö J. , Tanner-Salo U. , Vuorela A. , Alaluusua S. 
Published: December 2019

ABSTRACT

The production of bacteriocin-like inhibitory substances, mutacins, by mutans streptococci varies among isolates. To find if the degree of mutacin activity of an isolate was related to its transmission between mother and her child, 19 mothers and their 18-month- to 3-year-old children were sampled for their oral mutans streptococci. In addition, the stability of mutacin activity was studied with isolates from the mothers and with isolates from five unrelated 5-year-old children in 5- to 7-year follow-up studies. A total of 145 oral mutans streptococcal isolates were serotyped by immunodiffusion, ribotyped, and mutacin typed by the stab culture technique. Mutacin was produced by 88% of the strains against more than 1 of the 14 indicator strains, representing mutans streptococci,
Streptococcus sanguis
,
Streptococcus salivarius
,
Streptococcus oralis
,
Streptococcus gordonii
, and
Streptococcus pyogenes. Streptococcus mutans
isolates showed more inhibitory activity than did
Streptococcus sobrinus
isolates. Identical ribotypes had similar mutacin activity profiles within a subject, initially and in the follow-up studies, in all but two cases. The mothers harbored a total of 37 different mutans streptococcal ribotypes. Six children were negative for mutans streptococci. Transmission was probable in 9 of 20 mother-child pairs on the basis of the presence of identical strains, as determined by ribotyping and bacteriocin (mutacin) typing.
S. mutans
strains shared between a mother and her child showed a broader spectrum of inhibitory activity than did nontransmitted strains. In conclusion, the mutacin activity of clinical isolates is reasonably stable, and this virulence factor seems to be of clinical importance in early colonization by
S. mutans.
Experimental
Helicobacter pylori
Infection Induces Antral Gastritis and Gastric Mucosa-Associated Lymphoid Tissue in Guinea Pigs
Authors: Shomer Nirah H. , Dangler Charles A. , Whary Mark T. , Fox James G. 
Published: December 2019

ABSTRACT

Humans infected with
Helicobacter pylori
have abnormally low levels of the antioxidant vitamin C, which protects against the formation of carcinogenic nitrosamines, in gastric juice. Guinea pigs, like humans and nonhuman primates, have a dietary requirement for vitamin C. As such, these species have gastrointestinal vitamin C transport systems not found in other animals. We have developed and characterized a guinea pig model of chronic gastric
H. pylori
infection with the rodent-adapted Sydney strain of
H. pylori
. At 4 weeks postinfection, five of six animals of the infected group and zero of two animals of the control group were positive for
H. pylori
as determined by culture or PCR. At 15 weeks, six of six animals of the infected group and zero of two animals of the control group were positive.
H. pylori
-specific seroconversion was observed among infected animals. There were no histologic abnormalities in the gastric antra or fundi of control guinea pigs. In contrast, there was multifocal, mild to moderate lymphohistiocytic antral gastritis and formation of antral lymphoid follicles in
H. pylori
-infected animals. The lesion distribution in the gastric antra paralleled that observed in
H. pylori
-infected humans. The
H. pylori
-infected guinea pig should prove useful in modeling the interaction of helicobacter and vitamin C in gastric carcinogenesis.
Decorin-Binding Protein ofBorrelia burgdorferiIs Encoded within a Two-Gene Operon and Is Protective in the Murine Model of Lyme Borreliosis
Authors: Hagman Kayla E. , Lahdenne Pekka , Popova Taissia G. , Porcella Stephen F. , Akins Darrin R. , Radolf Justin D. , Norgard Michael V. 
Published: December 2019

ABSTRACTIsolated outer membranes ofBorrelia burgdorferiwere used in immunoblotting experiments with sera from immune mice to identify new putative Lyme disease vaccine candidates. One immunoreactive polypeptide migrated on polyacrylamide gels just proximal to outer surface protein C and comigrated with [3H]palmitate-labeled polypeptides. A degenerate oligonucleotide primer based upon internal amino acid sequence information was used to detect the corresponding gene within aB. burgdorferitotal genomic library. The relevant open reading frame (ORF) encoded a polypeptide comprised of a 24-amino-acid putative signal peptide terminated by LLISC, a probable consensus sequence for lipoprotein modification, and a mature protein of 163 amino acids. Immunoblots of a recombinant fusion protein corresponding to this ORF supported the idea that the encoded protein was a previously reported decorin-binding protein (DBP) ofB. burgdorferiN40 (B. P. Guo, S. J. Norris, L. C. Rosenberg, and M. Höök, Infect. Immun. 63:3467–3472, 1995). However, further DNA sequencing revealed the presence of a second ORF, designated ORF-1, whose termination codon was 119 bp upstream of thedbpgene. ORF-1 also encoded a putative lipoprotein with a mature length of 167 amino acids. Northern blots, Southern blots, and primer extension analyses indicated that ORF-1 anddbpcomprised a two-gene operon located on the 49-kb linear plasmid. Both proteins, which were 40% identical and 56% similar, partitioned into Triton X-114 detergent extracts ofB. burgdorferiisolated outer membranes. Mice infected withB. burgdorferiproduced high titers of antibodies against the ORF-1-encoded protein and DBP during both early and later stages of chronic infection. Both DBP and the ORF-1-encoded protein were sensitive to proteinase K treatment of intact borreliae, suggesting that they were surface exposed. In active immunization experiments, 78% of mice immunized with recombinant DBP were immune to challenge. While it is not clear whether the two lipoproteins encoded by the ORF-1-dbpoperon have analogous decorin-binding functions in vivo, the combined studies implicate DBP as a new candidate for a human Lyme disease vaccine.
Borrelia burgdorferiStimulates the Production of Interleukin-10 in Peripheral Blood Mononuclear Cells from Uninfected Humans and Rhesus Monkeys
Authors: Giambartolomei Guillermo H. , Dennis Vida A. , Philipp Mario T. 
Published: December 2019

ABSTRACTHeat-killedBorrelia burgdorferispirochetes stimulate in vitro production of interleukin-10 (IL-10) at both mRNA and protein levels in peripheral blood mononuclear cells (PBMC) of uninfected rhesus monkeys. A concomitant down-modulation of IL-2 gene transcription was observed. Neither IL-4 nor gamma interferon gene expression was ostensibly affected byB. burgdorferispirochetes. These phenomena were observed regardless of whether the stimulating spirochetes belonged to theB. burgdorferisensu stricto,Borrelia afzelii, orBorrelia gariniigenospecies, the three main species that cause Lyme disease.B. burgdorferialso induced production of IL-10 in uninfected human PBMC, indicating that this effect might play a role in human Lyme disease. Purified lipidated outer surface protein A (OspA), but not its unlipidated form, induced the production of high levels of IL-10 in uninfected human PBMC. Thus, the lipid moiety is essential in the induction of IL-10 in these PBMC.B. burgdorferiM297, a mutant strain that lacks the plasmid that encodes OspA and OspB, also induced IL-10 gene transcription in PBMC, indicating that this phenomenon is not causally linked exclusively to OspA and its lipid moiety. These results demonstrate thatB. burgdorferican stimulate the production of an antiinflammatory, immunosuppressive cytokine in naive cells and suggest that IL-10 may play a role both in avoidance by the spirochete of deleterious immune responses and in limiting the inflammation that the spirochete is able to induce.
Augmentation of Human Macrophage Candidacidal Capacity by Recombinant Human Myeloperoxidase and GranulocyteMacrophage Colony-Stimulating Factor
Authors: Maródi László , Tournay Christophe , Káposzta Rita , Johnston Richard B. , Moguilevsky Nicole 
Published: December 2019

ABSTRACTPhagocyte myeloperoxidase (MPO) is believed to be particularly important in defense against candida infection. We reported earlier that monocytes, rich in MPO, killedCandida albicansat a significantly higher rate and extent than did monocyte-derived macrophages, known to lack MPO, and thatC. albicansis less resistant to MPO-dependent oxidants than less pathogenicCandidaspecies. We hypothesized, therefore, that the capacity of macrophages to killC. albicansmight be improved in the presence of MPO. In this study, we evaluated the ability of recombinant human MPO (rhMPO) to augment the killing ofC. albicansby resident macrophages and macrophages activated by recombinant human granulocyte-macrophage colony-stimulating factor. Addition of rhMPO (concentration range, 0.8 to 6.4 U/ml) to suspensions of resident and activated macrophages and opsonizedC. albicansresulted in concentration-dependent and significant increases in candida killing. This enhancement was particularly pronounced with activated macrophages, whetherC. albicanswas opsonized or unopsonized and ingested through the macrophage mannose receptor. rhMPO did not affect the killing ofC. albicansby monocytes, nor did it affect phagocytosis of opsonized or unopsonizedC. albicans. These results indicate that exogenous rhMPO can augment the candidacidal capacity of both resident and activated macrophages, with a more profound effect on activated cells. We suggest that rhMPO may be effective in the treatment of invasive candidiasis.
Expanded CD14+CD16+Monocyte Subpopulation in Patients with Acute and Chronic Infections Undergoing Hemodialysis
Authors: Nockher Wolfgang Andreas , Scherberich Jürgen E. 
Published: December 2019

ABSTRACTInfections are frequent complications in end-stage renal failure patients undergoing hemodialysis (HD), and peripheral blood monocytes are important cells in host defense against infections. The majority of circulating monocytes express high levels of lipopolysaccharide receptor antigen CD14 and are negative for the immunoglobulin Fcγ receptor type III (CD16). We studied the occurrence of a minor subpopulation coexpressing low levels of CD14 together with CD16 in HD patients. In healthy controls CD14+CD16+monocytes account for 8% ± 4% of CD14+monocytes, with an absolute number of 29 ± 14 cells/μl. In stable HD patients the CD14+CD16+subpopulation was significantly elevated (14% ± 3%, or 66 ± 28 cells/μl), while the number of CD14++monocytes (monocytes strongly positive for CD14) remained constant. In HD patients suffering from chronic infections a further rise in CD14+CD16+monocytes was observed (128 ± 71 cells/μl;P< 0.01) such that this subpopulation constituted 24% of all blood monocytes. In contrast, numbers of CD14++cells did not change compared to those for stable HD patients, indicating that the CD14+CD16+monocyte subpopulation was selectively expanded. During acute infections the CD14+CD16+cell subpopulation always expanded. A whole-blood assay revealed that CD14+CD16+monocytes exhibited a higher phagocytosis rate forEscherichia colibacteria than CD14++monocytes, underlining their role during host defense. In addition, CD14+CD16+monocytes expressed higher levels of major histocompatibility complex (MHC) class II antigens (HLA-DR, -DP, and -DQ) and equal amounts of MHC class I antigens (HLA-ABC). Thus, CD14+CD16+cells constitute a potent phagocytosing and antigen-presenting monocyte subpopulation, which is expanded during acute and chronic infections commonly observed in chronic HD patients.
Pasteurella haemolyticaA1-Derived Leukotoxin and Endotoxin Induce Intracellular Calcium Elevation in Bovine Alveolar Macrophages by Different Signaling Pathways
Authors: Hsuan S. L. , Kannan M. S. , Jeyaseelan S. , Prakash Y. S. , Sieck G. C. , Maheswaran S. K. 
Published: December 2019

ABSTRACTLeukotoxin and endotoxin derived fromPasteurella haemolyticaserotype 1 are the primary virulence factors contributing to the pathogenesis of lung injury in bovine pneumonic pasteurellosis. Activation of bovine alveolar macrophages with endotoxin or leukotoxin results in the induction of cytokine gene expression, with different kinetics (H. S. Yoo, S. K. Maheswaran, G. Lin, E. L. Townsend, and T. R. Ames, Infect. Immun. 63:381–388, 1995; H. S. Yoo, B. S. Rajagopal, S. K. Maheswaran, and T. R. Ames, Microb. Pathog. 18:237–252, 1995). Furthermore, extracellular Ca2+is required for leukotoxin-induced cytokine gene expression. However, the involvement of Ca2+in endotoxin effects and the precise signaling mechanisms in the regulation of intracellular Ca2+by leukotoxin and endotoxin are not known. In fura-2-acetoxymethyl ester-loaded alveolar macrophages, intracellular Ca2+regulation by leukotoxin and endotoxin was studied by video fluorescence microscopy. Leukotoxin induced a sustained elevation of intracellular Ca2+in a concentration-dependent fashion by influx of extracellular Ca2+through voltage-gated channels. In the presence of fetal bovine serum, endotoxin elevated intracellular Ca2+even in the absence of extracellular Ca2+. Leukotoxin-induced intracellular Ca2+elevation was inhibited by pertussis toxin, inhibitors of phospholipases A2and C, and the arachidonic acid analog 5,8,11,14-eicosatetraynoic acid. Intracellular Ca2+elevation by endotoxin was inhibited by inhibitors of phospholipase C and protein tyrosine kinase, but not by pertussis toxin, or the arachidonic acid analog. To the best of our knowledge, this is the first report of Ca2+signaling by leukotoxin through a G-protein-coupled mechanism involving activation of phospholipases A2and C and release of arachidonic acid in bovine alveolar macrophages. Ca2+signaling by endotoxin, on the other hand, involves activation of phospholipase C and requires tyrosine phosphorylation. The differences in the Ca2+signaling mechanisms may underlie the reported temporal differences in gene expression during leukotoxin and endotoxin activation.
Expression of Two Members of the pMGA Gene Family of
Mycoplasma gallisepticum
Oscillates and Is Influenced by pMGA-Specific Antibodies
Authors: Markham Philip F. , Glew Michelle D. , Browning Glenn F. , Whithear Kevin G. , Walker Ian D. 
Published: December 2019

ABSTRACT

Certain monoclonal antibodies and polyclonal antisera directed to pMGA, the major protein of
Mycoplasma gallisepticum
, were tested for the ability to influence the surface phenotype of the cell population which resulted from their inclusion in growth medium. The polyclonal antiserum and one monoclonal antibody (MAb 66) resulted in an alteration of surface phenotype; specifically, populations of cells grown either on plates or in broth cultures which contained these reagents ceased the expression of pMGA and instead expressed an antigenically unrelated new polypeptide (p82). Upon the removal of antibody, the progeny of these cells regained pMGA expression and produced antigenically sectored colonies. The basis of this switch between pMGA
+
and pMGA
−
states was shown to be transcriptional. The p82 polypeptide, the expression of which resulted from growth of cells in antibodies, was another member of the pMGA gene family and was located just downstream from the pMGA gene normally expressed by the
M. gallisepticum
cells used. Collectively the results of this work suggest that this organism has evolved an unusual means of altering the antigenic composition of its surface in response to antibodies or to other environmental cues.
Isotypes and Opsonophagocytosis of Pneumococcus Type 6B Antibodies Elicited in Infants and Adults by an Experimental Pneumococcus Type 6B-Tetanus Toxoid Vaccine
Authors: Vidarsson Gestur , Sigurdardottir Sigurveig T. , Gudnason Thorolfur , Kjartansson Sveinn , Kristinsson Karl G. , Ingolfsdottir Gunnhildur , Jonsson Steinn , Valdimarsson Helgi , Schiffman Gerald , Schneerson Rachel , Jonsdottir Ingileif 
Published: December 2019

ABSTRACTStreptococcus pneumoniaeis a major respiratory pathogen of infants, children, and the elderly. Polysaccharide vaccines have been useful in adult populations but do not elicit protective immunity in infants and young children. To enhance their immunogenicity, vaccines of pneumococcal polysaccharides conjugated to proteins are being developed. In this study antibody levels and opsonic activities were compared in sera of infants and adults injected with pneumococcal polysaccharide type 6B (Pn6B) conjugated to tetanus toxoid (TT) (Pn6B-TT). Healthy infants were injected with Pn6B-TT; group A was injected at 3, 4, and 6 months of age, and group B was injected at 7 and 9 months of age. A booster injection was given at 18 months. Adults were injected once. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and their functional activities were measured by opsonophagocytosis of radiolabelled pneumococci. In adults, increases in immunoglobulin M (IgM), IgG, IgA, IgG1, and IgG2 to Pn6B were observed. Infants reached adult levels of IgG1 anti-Pn6B after the primary injections. After the booster injection the infant groups had total IgG- and IgM-Pn6B antibody levels similar to those of adults. After the booster injection, IgG1 was the dominant infant anti-Pn6B isotype and at a level higher than in vaccinated adults, but IgA and IgG2 antibodies remained at very low levels. Opsonic activity increased significantly after Pn6B-TT injections; the highest infant sera showed opsonic activity comparable to that of vaccinated adults. Overall, opsonic activity correlated best with total and IgG anti-Pn6B antibodies (r= 0.741,r= 0.653, respectively;n= 35) and was highest in sera with high levels of all Pn6B antibody isotypes. The results indicate the protective potential of a pneumococcal 6B polysaccharide protein conjugate vaccine for young infants.
Rectal and Intranasal Immunizations with Recombinant Urease Induce Distinct Local and Serum Immune Responses in Mice and Protect against
Helicobacter pylori
Infection
Authors: Kleanthous Harry , Myers Gwendolyn A. , Georgakopoulos Kathleen M. , Tibbitts Timothy J. , Ingrassia Jennifer W. , Gray Heather L. , Ding Ru , Zhang Zhen-Zi , Lei Wende , Nichols Richard , Lee Cynthia K. , Ermak Thomas H. , Monath Thomas P. 
Published: December 2019

ABSTRACT

To determine the optimal inductive sites for immunization against
Helicobacter pylori
infection, the protective efficacy of recombinant urease (rUre) was assessed for mice given the vaccine by either the oral (p.o.), intranasal (i.n.), or rectal route. When mice were immunized with rUre (25 μg p.o. or rectally or 10 μg i.n.) plus heat-labile toxin from
Escherichia coli
as the mucosal adjuvant, all routes afforded protection against challenge with
H. pylori
, as indicated by a significant reduction in gastric urease activity (
P
< 0.0005) compared to that of sham-immunized controls. Quantitative
H. pylori
culture of stomach tissue demonstrated a >97% reduction in bacterial burden in mice immunized by all routes (
P
< 0.05). Induction of antiurease immunoglobulin A (IgA) levels in gastric luminal secretions after p.o. immunization was greater than after i.n. administration (means, 6.0 and 1.02 ng/ml, respectively) and was dependent upon challenge with
H. pylori
. However, immunization by the rectal route resulted in the generation of the highest levels of gastric antiurease IgA (mean, 40.89 ng/ml), which was detectable prior to challenge with
H. pylori
. Immunohistochemical staining of stomach tissue for cells secreting urease-specific antibody and CD4
+
T cells showed levels of recruitment to be dependent upon challenge with
H. pylori
and equivalent for all routes. These results identify both the rectum and nasal passages as suitable inductive sites for urease immunization.