bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive Value of CD19 Measurements for Bacterial Infections in Children Infected with Human Immunodeficiency Virus
Authors: Betensky Rebecca A. , Calvelli Theresa , Pahwa Savita 
Published: December 2019

ABSTRACTWe investigated the predictive value of CD19 cell percentages (CD19%) for times to bacterial infections, using data from six pediatric AIDS Clinical Trials Group protocols and adjusting for other potentially prognostic variables, such as CD4%, CD8%, immunoglobulin (IgA) level, lymphocyte count, prior infections, prior zidovudine treatment, and age. In addition, we explored the combined effects of CD19% and IgG level in predicting time to infection. We found that a low CD19% is associated with a nonsignificant 1.2-fold increase in hazard of bacterial infection (95% confidence interval: 0.97, 1.49). In contrast, a high IgG level is associated with a nonsignificant 0.87-fold decrease in hazard of infection (95% confidence interval: 0.68, 1.12). CD4% was more prognostic of time to bacterial infection than CD19% or IgG level. Low CD19% and high IgG levels together lead to a significant (P< 0.01) 0.50-fold decrease in hazard (95% confidence interval: 0.35, 0.73) relative to low CD19% and low IgG levels. Similarly, in a model involving assay result changes (from baseline to 6 months) as well as baseline values, the effect of CD19% by itself is reversed from its effect in conjunction with IgG. In this model, CD19% that are increasing and high are associated with decreases in hazard of infection (P< 0.01), while increasing CD19% and increasing IgG levels are associated with significant (at theP= 0.01 level) fourfold increases in hazard of infection relative to stable CD19% and decreasing, stable, or increasing IgG levels. Our data suggest that CD19%, in conjunction with IgG level, provides a useful prognostic tool for bacterial infections. It is highly likely that T-helper function impacts on B-cell function; thus, inclusion of CD4% in such analyses may greatly enhance the assessment of risk for bacterial infection.
Streptokinase as a Mediator of Acute Post-Streptococcal Glomerulonephritis in an Experimental Mouse Model
Authors: Nordstrand Annika , Norgren Mari , Ferretti Joseph J. , Holm Stig E. 
Published: December 2019

ABSTRACTGroup A streptococcal infections are sometimes followed by the inflammatory kidney disease acute poststreptococcal glomerulonephritis (APSGN). To test the importance of streptokinase in the pathogenesis of this disease, isogenic strains of the nephritis isolate NZ131, differing only in the ability to produce streptokinase of the nephritis-associatedska1 genotype, were used for infection in a mouse tissue cage model for APSGN. Streptokinase production was found to be a prerequisite for the capacity of the strain to induce APSGN in mice. In addition, streptokinase was demonstrated in the kidneys of mice infected with the nephritogenic NZ131 and EF514 strains. After infection with the nonnephritogenic strain S84, neither streptokinase nor C3 deposition were observed. Deposition of streptokinase in the glomeruli was detected as soon as 4 days after infection. These findings provide support for the hypothesis that streptokinase initiates the nephritis process by glomerular deposition, which leads to local activation of the complement cascade. Detection of streptokinase in kidney tissue increased with the degree of glomerular hypercellularity. Thus, the severity of the pathological process may be a reflection of the degree of streptokinase deposition.
ToxR-Independent Expression of Cholera Toxin from the Replicative Form of CTXφ
Authors: Lazar Sara , Waldor Matthew K. 
Published: December 2019

ABSTRACT

The
ctxAB
operon, which encodes cholera toxin, resides in the genome of CTXφ, a filamentous bacteriophage. Within
Vibrio cholerae
cells, the CTXφ genome can exist either as a replicating plasmid or as a prophage integrated into the chromosome. Previous work established that ToxR is required for chromosomal
ctxAB
expression. We have learned that strains harboring the CTXφ replicative form produce cholera toxin under all conditions tested, independently of ToxR. During passage of CTXφ lysogens through the infant mouse intestine, transduction of CTXφ to a recipient strain can be detected, indicating that phage excision and replication occur in vivo. These results suggest that phage induction might provide a novel mechanism for the regulation of cholera toxin production.
Antigenic Analysis of
Bordetella pertussis
Filamentous Hemagglutinin with Phage Display Libraries and Rabbit Anti-Filamentous Hemagglutinin Polyclonal Antibodies
Authors: Wilson Dan R. , Siebers Annette , Finlay B. Brett 
Published: December 2019

ABSTRACT

Although substantial advancements have been made in the development of efficacious acellular vaccines against
Bordetella pertussis
, continued progress requires better understanding of the antigenic makeup of
B. pertussis
virulence factors, including filamentous hemagglutinin (FHA). To identify antigenic regions of FHA, phage display libraries constructed by using random fragments of the 10-kbp
Eco
RI fragment of
B. pertussis fhaB
were affinity selected with rabbit anti-FHA polyclonal antibodies. Characterization of antibody-reactive clones displaying FHA-derived peptides identified 14 antigenic regions, each containing one or more epitopes. A number of clones mapped within regions containing known or putative FHA adhesin domains and may be relevant for the generation of protective antibodies. The immunogenic potential of the phage-displayed peptides was assessed indirectly by comparing their recognition by antibodies elicited by sodium dodecyl sulfate (SDS)-denatured and native FHA and by measuring the inhibition of this recognition by purified FHA. FHA residues 1929 to 2019 may contain the most dominant linear epitope of FHA. Clones mapping to this region accounted for ca. 20% of clones recovered from the initial library selection and screening procedures. They are strongly recognized by sera against both SDS-denatured and native FHA, and this recognition is readily inhibited by purified FHA. Given also that this region includes a factor X homolog (J. Sandros and E. Tuomanen, Trends Microbiol. 1:192–196, 1993) and that the single FHA epitope (residues 2001 to 2015) was unequivocally defined in a comparable study by E. Leininger et al. (J. Infect. Dis. 175:1423–1431, 1997), peptides derived from residues of 1929 to 2019 of FHA are strong candidates for future protection studies.
Staphylococcus aureusSerotype 5 Capsular Polysaccharide Is Antiphagocytic and Enhances Bacterial Virulence in a Murine Bacteremia Model
Authors: Thakker Manoj , Park Jin-Sir , Carey Vincent , Lee Jean C. 
Published: December 2019

ABSTRACTControversy persists over the role that the capsular polysaccharide plays in the pathogenesis ofStaphylococcus aureusinfections. To address this issue, we compared the mouse virulence ofS. aureusReynolds and capsule-defective mutant strains cultivated under conditions of high or low capsule expression. Strain Reynolds cells cultivated on Columbia salt agar plates expressed ∼100-fold more type 5 capsular polysaccharide than did cells cultivated in Columbia salt broth. The relative virulence of strain Reynolds and its capsule-defective mutants after growth on either solid or liquid medium was examined in mice challenged intraperitoneally or intravenously. The results indicated that agar-grown Reynolds cells were cleared from the bloodstream of mice less readily than broth-grown Reynolds cells. When the parental and mutant strains were cultivated on solid medium, strain Reynolds sustained a higher level of bacteremia than did the capsular mutants. We performed in vitro opsonophagocytic killing assays to determine whether staphylococcal virulence for mice correlated with resistance to phagocytosis.S. aureusReynolds cultivated on solid medium was susceptible to phagocytic killing only in the presence of specific capsular antibodies and complement. Strain Reynolds grown in broth showed opsonic requirements for phagocytic killing that were similar to those of the capsular mutants (grown in broth or on agar); i.e., the bacteria were opsonized for phagocytosis by nonimmune serum with complement activity. These studies indicate that optimal expression of capsule enhances bacterial virulence in the mouse model of bacteremia, probably by rendering the organisms resistant to opsonophagocytic killing by leukocytes.
DbpA, but Not OspA, Is Expressed by
Borrelia burgdorferi
during Spirochetemia and Is a Target for Protective Antibodies
Authors: Cassatt David R. , Patel Nita K. , Ulbrandt Nancy D. , Hanson Mark S. 
Published: December 2019

ABSTRACT

DbpA is a target for antibodies that protect mice against infection by cultured
Borrelia burgdorferi
. Infected mice exhibit early and sustained humoral responses to DbpA and DbpB, suggesting that these proteins are expressed in vivo. Many antigens expressed in mammals by
B. burgdorferi
are repressed in vitro at lower growth temperatures, and we have now extended these observations to include DbpA and DbpB. To confirm that the protective antigen DbpA is expressed in vivo and to address the question of its accessibility to antibodies during infection, we examined
B. burgdorferi
in blood samples from mice following cutaneous inoculation.
B. burgdorferi
was visualized by dark-field microscopy in plasma samples from spirochetemic mice, and an indirect immunofluorescence assay showed that these spirochetes were DbpA positive and OspA negative. We developed an ex vivo borreliacidal assay to show that hyperimmune antiserum against DbpA, but not OspA, killed these plasma-derived spirochetes, demonstrating that DbpA is accessible to antibodies during this phase of infection. Blood transferred from spirochetemic donor mice readily established
B. burgdorferi
infection in naive recipient mice or mice hyperimmunized with OspA, while mice hyperimmunized with DbpA showed significant protection against challenge with host-adapted spirochetes. Antiserum from persistently infected mice had borreliacidal activity against both cultured and plasma-derived spirochetes, and adsorption of this serum with DbpA substantially depleted this killing activity. Our observations show that immunization with DbpA blocks
B. burgdorferi
dissemination from the site of cutaneous inoculation and suggest that DbpA antibodies may contribute to control of persistent infection.
Large-Scale Identification of Virulence Genes from
Streptococcus pneumoniae
Authors: Polissi Alessandra , Pontiggia Andrea , Feger Georg , Altieri Mario , Mottl Harald , Ferrari Livia , Simon Daniel 
Published: December 2019

ABSTRACT

Streptococcus pneumoniae
is the major cause of bacterial pneumonia, and it is also responsible for otitis media and meningitis in children. Apart from the capsule, the virulence factors of this pathogen are not completely understood. Recent technical advances in the field of bacterial pathogenesis (in vivo expression technology and signature-tagged mutagenesis [STM]) have allowed a large-scale identification of virulence genes. We have adapted to
S. pneumoniae
the STM technique, originally used for the discovery of
Salmonella
genes involved in pathogenicity. A library of pneumococcal chromosomal fragments (400 to 600 bp) was constructed in a suicide plasmid vector carrying unique DNA sequence tags and a chloramphenicol resistance marker. The recent clinical isolate G54 was transformed with this library. Chloramphenicol-resistant mutants were obtained by homologous recombination, resulting in genes inactivated by insertion of the suicide vector carrying a unique tag. In a mouse pneumonia model, 1.250 candidate clones were screened; 200 of these were not recovered from the lungs were therefore considered virulence-attenuated mutants. The regions flanking the chloramphenicol gene of the attenuated mutants were amplified by inverse PCR and sequenced. The sequence analysis showed that the 200 mutants had insertions in 126 different genes that could be grouped in six classes: (i) known pneumococcal virulence genes; (ii) genes involved in metabolic pathways; (iii) genes encoding proteases; (iv) genes coding for ATP binding cassette transporters; (v) genes encoding proteins involved in DNA recombination/repair; and (vi) DNA sequences that showed similarity to hypothetical genes with unknown function. To evaluate the virulence attenuation for each mutant, all 126 clones were individually analyzed in a mouse septicemia model. Not all mutants selected in the pneumonia model were confirmed in septicemia, thus indicating the existence of virulence factors specific for pneumonia.
Differences in Immune Responses Induced by Oral and Rectal Immunizations withSalmonella typhiTy21a: Evidence for Compartmentalization within the Common Mucosal Immune System in Humans
Authors: Kantele A. , Häkkinen M. , Moldoveanu Z. , Lu A. , Savilahti E. , Alvarez R. D. , Michalek S. , Mestecky J. 
Published: December 2019

ABSTRACTBased on the concept of the common mucosal immune system, immunization at various inductive sites can induce an immune response at other, remote mucosal surfaces. The immune responses elicited through rectal and oral routes of antigen delivery were compared with respect to (i) measurement of antibody responses in serum and various external secretions of the vaccinees and (ii) characterization of the nature and homing potentials of circulating antibody-secreting cells (ASC). Specific ASC appeared in the circulation in 4 of 5 volunteers after oral and 9 of 11 volunteers after rectal immunization withSalmonella typhiTy21a. The kinetics, magnitude, and immunoglobulin isotype distribution of the ASC responses were similar in the two groups. In both groups, almost all ASC (99 or 95% after oral or rectal immunization, respectively) expressed α4β7, the gut homing receptor (HR), whereasl-selectin, the peripheral lymph node HR, was expressed only on 22 or 38% of ASC, respectively. Oral immunization elicited a more pronounced immune response in saliva and vaginal secretion, while rectal immunization was more potent in inducing a response in nasal secretion, rectum, and tears. No major differences were found in the abilities of the two immunization routes to induce a response in serum or intestinal secretion. Thus, the rectal antigen delivery should be considered as an alternative to the oral immunization route. The different immune response profiles found in various secretions after oral versus rectal antigen administration provide evidence for a compartmentalization within the common mucosal immune system in humans.
Flagellins, but Not Endoflagellar Sheath Proteins, ofTreponema pallidumand of Pathogen-Related Oral Spirochetes Are Glycosylated
Authors: Wyss C. 
Published: December 2019

ABSTRACTGlycosylation of the flagellar core proteins (FlaBs) was detected inTreponema pallidumNichols and in the type or reference strains of seven oralTreponemaspecies. In several nonmotile strains of oral treponemes, the FlaBs were undetectable by both antibody and glycan staining. In contrast, a spontaneous low-motility variant ofT. vincenti£i-related strain RitzA, OMZ 305A, lacked the flagellar sheath protein (FlaA) and the two glycan-staining FlaB bands of the wild type, but antibody labeling revealed a novel FlaB band with a lower relative molecular weight. A ca. 38-kDa component of isolated endoflagella of T. vincentiiOMZ 800 was identified on Western blots as FlaA by monoclonal antibody (MAb) H9-2, which specifically labels the 37-kDa FlaA protein ofT. pallidum. Glycan and H9-2 labeling patterns similar to those ofT. pallidumwere observed in whole-cell extracts ofT. mediumG7201 and of 10 strains classified asT. vincentiiand as twoT. vincentii-related taxons. These four groups were thus identified as cultivable pathogen (T. pallidum)-related oral spirochetes as defined by labeling with MAb H9-2. No H9-2 MAb-reactive component could be detected inT. amylovorum,T. denticola,T. maltophilum,T. pectinovorum, and the three subspecies ofT. socranskii.
Salmonella typhimuriumInfection in Mice Induces Nitric Oxide-Mediated Immunosuppression through a Natural Killer Cell-Dependent Pathway
Authors: Schwacha Martin G. , Meissler Joseph J. , Eisenstein Toby K. 
Published: December 2019

ABSTRACTSplenocytes isolated from C57BL/6J female mice 3 to 7 days after inoculation with an attenuated strain ofSalmonella typhimuriumproduced high levels of nitric oxide (39 to 77 μM) and gamma interferon (IFN-γ). Additionally, spleen cell cultures fromSalmonella-inoculated mice were markedly suppressed in their ability to generate an in vitro plaque-forming cell (PFC) response to sheep erythrocytes. Depletion of natural killer (NK) cells from the immune splenocyte population markedly reduced nitric oxide production, prevented suppression of PFC responses, and completely abrogated IFN-γ release. Treatment of NK cell-depleted immune cells with IFN-γ restored nitric oxide production to levels comparable to those of intact immune cells and also restored the immunosuppression. These results suggest that NK cells regulate the induction of nitric oxide-mediated immunosuppression following infection withS. typhimuriumthrough the production of IFN-γ.
Structural Requirements for Glycosaminoglycan Recognition by the Lyme Disease Spirochete,
Borrelia burgdorferi
Authors: Leong John M. , Robbins Douglas , Rosenfeld Louis , Lahiri Biswajit , Parveen Nikhat 
Published: December 2019

ABSTRACT

Borrelia burgdorferi
, the Lyme disease agent, binds glycosaminoglycans (GAGs) such as heparin, heparan sulfate, and dermatan sulfate. Heparin or heparan sulfate fractions separated by size or charge were tested for their ability to inhibit attachment of
B. burgdorferi
to Vero cells. GAG chains of increasing length and/or charge showed increasing inhibitory potency, and detectable heparin inhibition of bacterial binding required a minimum of 16 residues. The ability of a given heparin fraction to inhibit binding to Vero cells was strongly predictive of its ability to inhibit hemagglutination, suggesting that hemagglutination reflects the capacity of
B. burgdorferi
to bind to GAGs.
Comparison of the Abilities of Different AttenuatedSalmonella typhimuriumStrains To Elicit Humoral Immune Responses against a Heterologous Antigen
Authors: Dunstan Sarah J. , Simmons Cameron P. , Strugnell Richard A. 
Published: December 2019

ABSTRACTWe compared the abilities of differentSalmonella entericavar. Typhimurium (S. typhimurium) strains harboring mutations in the genesaroA,aroAD,purA,ompR,htrA, andcya crpto present the heterologous antigen, C fragment of tetanus toxin, to the mouse immune system. Plasmid pTETtac4, encoding C fragment, was transferred into the variousS. typhimuriummutants, and the levels of antigen expression were found to be equivalent. After primary oral immunization of BALB/c mice, all attenuated strains were capable of penetrating the gut epithelium and colonizing the Peyer’s patches and spleens of mice. Of all strains compared, the ΔpurAmutant colonized and persisted in the Peyer’s patches at the lowest level, whereas the ΔhtrAmutant colonized and persisted in the spleen at the lowest level. The level of specific antibody elicited by the different strains against eitherS. typhimuriumlipopolysaccharide or tetanus toxoid was strain dependent and did not directly correlate to the mutants’ ability to colonize the spleen. The level of immunoglobulin G1 (IgG1) and IgG2a antibody specific for tetanus toxoid was determined in mice immunized with fourS. typhimuriummutants. The level of antigen-specific IgG1 and IgG2a was significantly lower in animals immunized withS. typhimuriumΔpurA. Antigen-specific T-cell proliferation assays indicated a degree of variability in the capacity of some strains to elicit T cells to the heterologous antigen. Cytokine profiles (gamma interferon and interleukin-5) revealed that the fourS. typhimuriummutants tested induced a Th1-type immune response. Mice were challenged with a lethal dose of tetanus toxin 96 days after oral immunization. With the exception of theS. typhimuriumΔpurAmutant, all strains elicited a protective immune response. These data indicate that the level of total Ig specific for the carried antigen, C fragment, does not correlate with the relative invasiveness of the vector, but it is determined by the carrier mutation and the background of theS. typhimuriumstrain.
Increased Resistance to
Taenia crassiceps
Murine Cysticercosis in Qa-2 Transgenic Mice
Authors: Fragoso Gladis , Lamoyi Edmundo , Mellor Andrew , Lomelí Ciro , Hernández Marisela , Sciutto Edda 
Published: December 2019

ABSTRACT

We previously reported important differences in resistance to
Taenia crassiceps
murine cysticercosis between BALB/c substrains. It was suggested that resistance might correlate with expression of the nonclassic class I major histocompatibility complex (MHC) Qa-2 antigen; BALB/cAnN is Qa-2 negative and highly susceptible to
T. crassiceps
, whereas BALB/cJ expresses Qa-2 and is highly resistant. In this study, we investigated the role of Qa-2 in mediating resistance to cysticercosis by linkage analysis and infection of Qa-2 transgenic mice. In BALB/cAnN × (C57BL/6J × BALB/cAnN)F
1
and BALB/cAnN × (BALB/cJ × BALB/cAnN)F
1
backcrosses, the expression of Qa-2 antigen correlated with resistance to cysticercosis. Significantly fewer parasites were recovered from infected Qa-2 transgenic male and female mice than from nontransgenic mice of similar genetic background. These results clearly demonstrate that the Qa-2 MHC antigen is involved in resistance to
T. crassiceps
cysticercosis.
Growth of Virulent and AvirulentMycobacterium tuberculosisStrains in Human Macrophages
Authors: Zhang Ming , Gong Jianhua , Lin Yuanguang , Barnes Peter F. 
Published: December 2019

ABSTRACTMycobacterium tuberculosisH37Rv causes progressive disease in animals, whereas the H37Ra strain does not. The relevance of this difference in virulence to human infection is uncertain because these strains have been shown to have similar growth rates in human macrophages. To evaluate the intracellular growth ofM. tuberculosisstrains in macrophages under conditions similar to those encountered in vivo, we infected human monocyte-derived macrophages with H37Ra, H37Rv, or one of four isolates from tuberculosis patients at a low bacillus-to-macrophage ratio. H37Rv and the patient isolates grew significantly faster than H37Ra, based on the numbers of CFU and acid-fast bacilli. These findings did not result from extracellular mycobacterial growth, differential macrophage viability, or bacillary clumping. In contrast to other published results, these findings indicate that the virulence characteristics ofM. tuberculosisstrains in animal models are relevant to human tuberculosis infection.
Granulocyte-Macrophage Colony-Stimulating Factor inStaphylococcus aureus-Induced Arthritis
Authors: Verdrengh Margareta , Tarkowski Andrej 
Published: December 2019

ABSTRACTGranulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that is able to increase not only the production of phagocytic cells but also their efficacy with respect to, e.g., bactericidal properties. In this study, we wanted to analyze the impact of GM-CSF on experimentalStaphylococcus aureus-induced arthritis. For that purpose, mice were administered GM-CSF before and after bacterial inoculation. Although there was an increase in the total number of leukocytes as well as in the granulocyte fraction, there was no favorable effect on the severity of arthritis or on survival rates. There were no obvious differences between the GM-CSF-pretreated animals and controls with regard to growth of staphylococci in joints and kidneys 4 days after the bacterial inoculation. In contrast, mice that had been pretreated with GM-CSF prior to bacterial inoculation showed approximately four times lower numbers of bacteria in their blood 24 h later. These results, along with those of our previous studies, suggest that on the one hand the granulocyte is the main protective cell during the course ofS. aureusinfection but that on the other hand, upregulation of granulocyte-macrophage production will not exert any additional protective effects with respect to tissue injury.