bluuebunny/crossref_metadata_2025_split huggingface dataset:
Siderophore Production by Cystic Fibrosis Isolates of
Burkholderia cepacia
Authors: Darling Patricia , Chan Maria , Cox Andrew D. , Sokol Pamela A. 
Published: December 2019

ABSTRACT

Sixty-one
Burkholderia cepacia
isolates from patients with cystic fibrosis (CF) and four plant isolates were screened for production of the siderophores salicylic acid (SA), pyochelin, cepabactin, and ornibactins and fingerprinted by a PCR-based randomly amplified polymorphic DNA (RAPD) method. Of the 24 RAPD types determined, 22 (92%) were associated with isolates that produced SA, 21 (87%) were associated with isolates that produced ornibactins, 15 (60%) were associated with isolates that produced pyochelin, and 3 (12%) were associated with isolates that produced cepabactin. Of the 24 RAPD types plus 2 phenotypic variants of types 1 and 9, 3 were associated with isolates that produced all four siderophores, 8 were associated with isolates that produced three siderophores, 12 were associated with isolates that produced two siderophores, and 3 were associated with isolates that produced only one siderophore. These results suggest that the numbers and types of siderophores produced by CF isolates of
B. cepacia
correlate with RAPD type and that SA and ornibactins are the most prevalent siderophores produced.
Role of Arg-Gingipain A in Virulence of
Porphyromonas gingivalis
Authors: Tokuda Masayuki , Karunakaran Thonthi , Duncan Margaret , Hamada Nobushiro , Kuramitsu Howard 
Published: December 2019

ABSTRACT

In order to access the role of the
Porphyromonas gingivalis
Arg-gingipain proteases in the virulence of this organism, a mutant defective in the
rgpA
gene was constructed in strain 381. This mutant, MT10, displayed only 40% of the Arg-specific cysteine protease activity of the wild-type strain. In addition, MT10, as well as the recently characterized protease mutant G-102, which is defective in the
rgpB
gene, displayed reduced self-aggregation, hemagglutination, and the ability to bind to immobilized type I collagen compared to levels of the wild-type parent. However, unlike mutant G-102, the
rgpA
mutant displayed increased binding to epithelial cells relative to that of the parental organism. Mutant MT10 also did not express detectable levels of the FimA protein as assessed by both Western and Northern blotting or fimbriae visible by electron microscopy of the cells. Furthermore, the ability of MT10 to degrade rat tail collagen fibers when it was cultured at 37°C was markedly attenuated compared to that of strain 381. These results suggest that Arg-gingipain A may play a significant role in the pathogenicity of
P. gingivalis
by altering the colonization and toxic properties of the organism.
Human T-Cell Responses after Vaccination with the Norwegian Group B Meningococcal Outer Membrane Vesicle Vaccine
Authors: Næss Lisbeth Meyer , Oftung Fredrik , Aase Audun , Wetzler Lee M. , Sandin Randi , Michaelsen Terje E. 
Published: December 2019

ABSTRACTWe have analyzed human T-cell responses in parallel with serum immunoglobulin G (IgG) antibody levels after systemic vaccination with the Norwegian group BNeisseria meningitidisouter membrane vesicle (OMV) vaccine. Ten adult volunteers, with no or very low levels of serum IgG antibodies against meningococci, received three doses intramuscularly of the OMV vaccine (at weeks 0, 6, and 46). T-cell proliferation against the OMV vaccine, purified outer membrane proteins (PorA and PorB), and control antigens (Mycobacterium bovisBCG vaccine and tetanus toxoid) was measured by thymidine incorporation of peripheral blood mononuclear cells before and after vaccination. The results showed that vaccination with OMV elicits strong primary and booster T-cell responses specific to OMV as well as the PorA (class 1) protein and significant, but markedly lower, responses against the PorB (class 3) protein. The median responses to OMV and PorA were 26 and 16 times the prevaccination levels, respectively. Most of the vaccinees showed low T-cell responses against OMV and PorA before vaccination, and the maximum T-cell responses to all vaccine antigens were usually obtained after the second vaccine dose. We found a positive correlation between T-cell responses and anti-OMV IgG antibody levels (r= 0.50,P< 0.0001, for OMV and PorA). In addition, we observed a progressive increase in the percentage of CD45R0+(memory) CD4-positive T cells (P= 0.002). In conclusion, we have shown that the Norwegian OMV vaccine against meningococcal B disease induced antigen-specific T-cell responses, kinetically accompanied by serum IgG responses, and that vaccination increased the proportion of memory T-helper cells.
Immunoglobulins to Group A Streptococcal Surface Molecules Decrease Adherence to and Invasion of Human Pharyngeal Cells
Authors: Fluckiger U. , Jones K. F. , Fischetti V. A. 
Published: December 2019

ABSTRACTThe M protein is one of the most important virulence factors of group A streptococci (Streptococcus pyogenes) and may play an important role in the first steps of streptococcal infection. Since acute pharyngitis is a frequently occurring infectious disease caused by these bacteria, we wished to know whether antibodies to the M protein or other surface components inhibit adherence and internalization of streptococci to pharyngeal cells. We investigated the role of whole human secretory immunoglobulin A (sIgA), M6 protein-specific sIgA, and M6 protein-specific serum IgG in the inhibition of streptococcal adherence and internalization to cultured human pharyngeal cells.S. pyogenesD471, which produces a type 6 M protein (M+), and its isogenic M-negative (M−) derivative JRS75 were tested. Purified whole sIgA, M protein-specific sIgA, and sIgA preabsorbed with M protein were able to decrease significantly the adherence of streptococci to pharyngeal cells. Purified IgG against the M6 protein did not diminish the attachment of streptococci to the pharyngeal cells but did reduce internalization. Thus, our data suggest that secretory IgA may play a key role in preventing streptococcal infection at mucosal surfaces by blocking adherence while affinity-purified anti-M protein-specific IgG blocks epitopes responsible for invasion.
An Essential Role for Gamma Interferon in Innate Resistance toShigella flexneriInfection
Authors: Way Sing Sing , Borczuk Alain C. , Dominitz Rene , Goldberg Marcia B. 
Published: December 2019

ABSTRACTShigellaspp. are the major cause of bacillary dysentery worldwide. To identify immune effectors associated with protection of the naive host during infection, the susceptibility to pulmonaryShigellainfection of each of various mouse strains that have a targeted deletion in a specific aspect of the immune system was evaluated. Our results demonstrate that mice deficient in gamma interferon are 5 orders of magnitude more susceptible toShigellathan are wild-type mice, whereas mice deficient in B and T lymphocytes or in T lymphocytes alone exhibit no difference in susceptibility. Significantly lower numbers of shigellae were recovered from immunocompetent compared with gamma-interferon-deficient mice after infection. While immunocompetent mice were able to clear a sublethalShigellainoculum by day 5 postinfection, progressively increasing numbers of shigellae were cultured from the lungs of gamma interferon-deficient mice over the same period. Histopathology of the lungs from immunocompetent mice infected with a sublethalShigellainoculum showed mild inflammatory changes, whereas the lungs from gamma interferon-deficient mice demonstrated progressively worsening acute bronchiolitis with ulceration. Further, the time to death in gamma interferon-deficient mice correlates inversely with the size of theShigellainoculum. To identify the cellular source of gamma interferon, we infected SCID mice, T-cell-receptor-deficient mice, beige mice (a mouse strain deficient in natural killer [NK] cell activity), and mice depleted of NK cells using anti-asialo-GM1. Each NK cell-deficient mouse strain exhibited a 10-fold-greater susceptibility toShigellainfection than immunocompetent mice. To test the protective effects of gamma interferon in vitro, survival of intracellularShigellawas examined in primary macrophages from wild-type mice, primary macrophages from gamma interferon-deficient mice, a macrophage cell line, and a fibroblast cell line. Following activation with gamma interferon, each cell type eradicated intracellularShigella, while nonactivated macrophages fosteredShigellareplication and nonactivated fibroblast cells fostered bothShigellareplication and intercellular spread. Taken together, these data establish that NK cell-mediated gamma interferon is essential to resistance following primaryShigellainfection.
A New Member of the S-Layer Protein Family: Characterization of the
crs
Gene from
Campylobacter rectus
Authors: Wang Beinan , Kraig Ellen , Kolodrubetz David 
Published: December 2019

ABSTRACT

Strains of the periodontal pathogen
Campylobacter rectus
express a 150- to 166-kDa protein on their cell surface. This protein forms a paracrystalline lattice, called the surface layer (S-layer), on the outer membrane of this gram-negative bacterium. To initiate a genetic analysis of the function of the S-layer in the pathogenesis of
C. rectus
, we have cloned and characterized its gene. The S-layer gene (
crs
) from
C. rectus
314 encodes a cell surface protein which does not have a cleaved signal peptide at its amino terminus. Although the amino acid sequence deduced from the
crs
gene has 50% identity with the amino-terminal 30 amino acids of the four S-layer proteins from
Campylobacter fetus
, the similarity decreases to less than 16% over the rest of the protein. Thus, the
crs
gene from
C. rectus
encodes a novel S-layer protein whose precise role in pathogenesis may differ from that of S-layer proteins from other organisms. Southern and Northern blot analyses with probes from different segments of the
crs
gene indicate that the S-layer gene is a single-copy, monocistronic gene in
C. rectus
. RNA end mapping and sequence analyses were used to define the
crs
promoter; there is an exact match to the
Escherichia coli
−10 promoter consensus sequence but only a weak match to the −35 consensus element. Southern blots of DNA from another strain of
C. rectus
, ATCC 33238, demonstrated that the
crs
gene is also present in that strain but that there are numerous restriction fragment length polymorphisms in the second half of the gene. This finding suggests that the carboxy halves of the S-layer proteins from strains 314 and 33238 differ. It remains to be determined whether the diversities in sequence are reflected in functional or antigenic differences important for the pathogenesis of different
C. rectus
isolates.
Comparison of an Adherence Domain and a Structural Region ofStreptococcus mutansAntigen I/II in Protective Immunity against Dental Caries in Rats after Intranasal Immunization
Authors: Hajishengallis George , Russell Michael W. , Michalek Suzanne M. 
Published: December 2019

ABSTRACTPrevious studies have identified an N-terminal saliva-binding region (SBR) onStreptococcus mutanssurface antigen I/II (AgI/II) and suggested its importance in the initial adherence ofS. mutansto saliva-coated tooth surfaces and subsequent development of dental caries. In this study, we compared the SBR with a C-terminal structural region of AgI/II (AgII) in their abilities to induce protective immunity against caries in rats. When SBR, AgII, or the whole AgI/II molecule was administered intranasally as a conjugate with the B subunit of cholera toxin (CT), in the presence of CT adjuvant, substantial levels of salivary immunoglobulin A anti-AgI/II antibodies were induced. Evaluation of caries activity showed that the SBR, though not as protective as the parent molecule, was superior to AgII and thus can be further considered as a component in a multivalent caries vaccine.
Cytokine Induction in Murine Macrophages Infected with Virulent and Avirulent
Rhodococcus equi
Authors: Giguère Steeve , Prescott John F. 
Published: December 2019

ABSTRACT

To look for a possible correlation between the virulence of
Rhodococcus equi
and its cytokine-inducing capacity, we evaluated intracellular survival and measured cytokine induction by mouse macrophages infected with a virulent strain containing an 85-kb plasmid and expressing VapA (103
+
), its avirulent plasmid-cured derivative (103
−
), and heat-killed 103
+
(HK). After incubation with similar numbers of bacteria, macrophages infected with 103
−
contained significantly more organisms than those infected with 103
+
or HK. The number of bacteria in the macrophages infected with 103
−
and HK decreased progressively, whereas the 103
+
numbers remained constant over 48 h. Interleukin 1β (IL-1β), IL-6, IL-10, IL-12 p40, and tumor necrosis factor alpha (TNF-α) mRNA induction peaked at 4 h and returned to baseline between 12 and 48 h postinfection. IL-1β, IL-6, IL-10, and TNF-α concentrations assessed by enzyme-linked immunosorbent assay generally agreed well with mRNA expression; IL-12 could, however, not be detected. For all the cytokines detected, mean concentrations in the supernatants were consistently higher in the 103
−
-infected monolayers than in those infected with 103
+
, although, with the exception of IL-1β, the differences were not statistically significant.
R. equi
HK was a poor inducer of cytokine production. In conclusion, virulent and avirulent
R. equi
strains induced similar levels of cytokine synthesis. The slightly greater induction of most cytokines observed following infection with 103
−
is likely secondary to greater uptake by macrophages rather than to a direct role of VapA or another plasmid-encoded product in downregulating cytokine induction.
Pasteurella haemolyticaLeukotoxin-Induced Increase in Phospholipase A2Activity in Bovine Neutrophils
Authors: Wang Zuncai , Clarke Cyril , Clinkenbeard Kenneth 
Published: December 2019

ABSTRACTExposure of bovine neutrophils toPasteurella haemolyticaleukotoxin (LKT) stimulates the production of leukotriene B4(LTB4), which is believed to be an important chemotactic agent in the development of acute fibrinopurulent pneumonic infection in cattle. The involvement of phospholipase A2(PLA2) in LKT-induced synthesis of LTB4was studied by using bovine neutrophils labeled with3H-arachidonate ([3H]AA). Incubation of isolated neutrophils with [3H]AA resulted in incorporation of radioactivity in the PLA2substrates phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine. Exposure of radiolabeled neutrophils to LKT caused concentration- and time-dependent release of radioactivity and redistribution of radioactivity in neutrophil membranes consistent with utilization of phosphoglyceride substrate and release of free fatty acid and eicosanoid products. These LKT-induced effects could be inhibited by pretreatment with arachidonyl trifluoromethyl ketone, an inhibitor of type IV cytoplasmic PLA2, and were dependent on extracellular calcium. These results support the conclusion that LKT-induced synthesis of LTB4involves a calcium-mediated increase in PLA2activity.
Involvement of T Cells in Enhanced Resistance toKlebsiella pneumoniaeSepticemia in Mice Treated with Liposome-Encapsulated Muramyl Tripeptide Phosphatidylethanolamine or Gamma Interferon
Authors: ten Hagen Timo L. M. , van Vianen Wim , Savelkoul Huub F. J. , Heremans Hubertine , Buurman Wim A. , Bakker-Woudenberg Irma A. J. M. 
Published: December 2019

ABSTRACTWe have previously shown that prophylactic administration of the liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine (MTPPE) and gamma interferon (IFN-γ) results in strongly increased survival of mice from a normally lethal septicemia withKlebsiella pneumoniae. It was anticipated that the treatment acts on macrophages and nonspecifically augments host resistance to various infections. In the present study, we provide evidence for a key role for T cells in host defense potentiation by the liposomal immunomodulators towardK. pneumoniaesepticemia. It is shown that both CD4 and CD8 cells are important in immunomodulation, most likely due to production of IFN-γ. Depletion of circulating IFN-γ resulted in strong reduction of the antimicrobial host defense activation. Administration of interleukin-10 resulted in decreased antimicrobial host defense activation by liposomal immunomodulators. Moreover, administration of liposomal immunomodulators was shown to induce predominantly T-helper type 1 (Th1) cell populations in the spleen. These findings indicate that immunomodulation with liposomal MTPPE and IFN-γ favors Th1 and NK cell activation.
Burkholderia cepacia
Produces a Hemolysin That Is Capable of Inducing Apoptosis and Degranulation of Mammalian Phagocytes
Authors: Hutchison Michael L. , Poxton Ian R. , Govan John R. W. 
Published: December 2019

ABSTRACT

Burkholderia cepacia
is an opportunistic pathogen that has become a major threat to individuals with cystic fibrosis (CF). In approximately 20% of patients, pulmonary colonization with
B. cepacia
leads to cepacia syndrome, a fatal fulminating pneumonia sometimes associated with septicemia. It has been reported that culture filtrates of clinically derived strains of
B. cepacia
are hemolytic. In this study, we have characterized a factor which contributes to this hemolytic activity and is secreted from
B. cepacia
J2315, a representative of the virulent and highly transmissible strain belonging to the recently described genomovar III grouping. Biochemical data from the described purification method for this hemolysin allows us to hypothesize that the toxin is a lipopeptide. As demonstrated for other lipopeptide toxins, the hemolysin from
B. cepacia
was surface active and lowered the surface tension of high-pressure liquid chromatography-grade water from 72.96 to 29.8 mN m
−1
. Similar to reports for other pore-forming cytotoxins, low concentrations of the hemolysin were able to induce nucleosomal degradation consistent with apoptosis in human neutrophils and the mouse-derived macrophage-type cell line J774.2. Exposure of human neutrophils to higher concentrations of toxin resulted in increased activities of the neutrophil degranulation markers cathepsin G and elastase. Based on the results obtained in this study, we suggest a role that allows
B. cepacia
to thwart the immune response and a model of the events that may contribute to the severe inflammatory response in the lungs of CF patients.
Characterization of the Roles of Hemolysin and Other Toxins in Enteropathy Caused by Alpha-Hemolytic
Escherichia coli
Linked to Human Diarrhea
Authors: Elliott Simon J. , Srinivas S. , Albert M. John , Alam Khorshed , Robins-Browne Roy M. , Gunzburg Stuart T. , Mee Brian J. , Chang Barbara J. 
Published: December 2019

ABSTRACT

Escherichia coli
strains producing alpha-hemolysin have been associated with diarrhea in several studies, but it has not been clearly demonstrated that these strains are enteropathogens or that alpha-hemolysin is an enteric virulence factor. Such strains are generally regarded as avirulent commensals. We examined a collection of diarrhea-associated hemolytic
E. coli
(DHEC) strains for virulence factors. No strain produced classic enterotoxins, but they all produced an alpha-hemolysin that was indistinguishable from that of uropathogenic
E. coli
strains. DHEC strains also produced other toxins including cytotoxic necrotizing factor 1 (CNF1) and novel toxins, including a cell-detaching cytotoxin and a toxin that causes HeLa cell elongation. DHEC strains were enteropathogenic in the RITARD (reversible intestinal tie adult rabbit diarrhea) model of diarrhea, causing characteristic enteropathies, including inflammation, necrosis, and colonic cell hyperplasia in both small and large intestines. Alpha-hemolysin appeared to be a major virulence factor in this model since it conferred virulence to nonpathogenic
E. coli
strains. Other virulence factors also appear to be contributing to virulence. These findings support the epidemiologic link to diarrhea and suggest that further research into the role of DHEC and alpha-hemolysin in enteric disease is warranted.
Opsonic Antibodies to the Surface M Protein of Group A Streptococci in Pooled Normal Immunoglobulins (IVIG): Potential Impact on the Clinical Efficacy of IVIG Therapy for Severe Invasive Group A Streptococcal Infections
Authors: Basma Hesham , Norrby-Teglund Anna , McGeer Allison , Low Donald E. , El-Ahmedy Omar , Dale James B. , Schwartz Benjamin , Kotb Malak 
Published: December 2019

ABSTRACTThe surface M protein of group A streptococci (GAS) is one of the major virulence factors for this pathogen. Antibodies to the M protein can facilitate opsonophagocytosis by phagocytic cells present in human blood. We investigated whether pooled normal immunoglobulin G (IVIG) contains antibodies that can opsonize and enhance the phagocytosis of type M1 strains of GAS and whether the levels of these antibodies vary for different IVIG preparations. We focused on the presence of anti-M1 antibodies because the M1T1 serotype accounts for the majority of recent invasive GAS clinical isolates in our surveillance studies. The level of anti-M1 antibodies in three commercial IVIG preparations was determined by enzyme-linked immunosorbent assay (ELISA), and the opsonic activity of these antibodies was determined by neutrophil-mediated opsonophagocytosis of a representative M1T1 isolate. High levels of opsonic anti-M1 antibodies were found in all IVIG preparations tested, and there was a good correlation between ELISA titers and opsonophagocytic activity. However, there was no significant difference in the levels of opsonic anti-M1 antibodies among the various IVIG preparations or lots tested. Adsorption of IVIG with M1T1 bacteria removed the anti-M1 opsonic activity, while the level of anti-M3 opsonophagocytosis was unchanged. Plasma was obtained from seven patients with streptococcal toxic shock syndrome who received IVIG therapy, and the level of anti-M1 antibodies was assessed before and after IVIG administration. A significant increase in the level of type M1-specific antibodies was found in the plasma of all patients who received IVIG therapy (P< 0.006). The results reveal another potential mechanism by which IVIG can ameliorate severe invasive group A streptococcal infections.