bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipooligosaccharide Structure Contributes to Multiple Steps in the Virulence ofNeisseria meningitidis
Authors: Plant Laura , Sundqvist Johanna , Zughaier Susu , Lövkvist Lena , Stephens David S. , Jonsson Ann-Beth 
Published: January 2006

ABSTRACTLipooligosaccharide (LOS) ofNeisseria meningitidishas been implicated in meningococcal interaction with host epithelial cells and is a major factor contributing to the human proinflammatory response to meningococci. LOS mutants of the encapsulatedN. meningitidisserogroup B strain NMB were used to further determine the importance of the LOS structure in in vitro adherence and invasion of human pharyngeal epithelial cells by meningococci and to study pathogenicity in a mouse (CD46 transgenic) model of meningococcal disease. The wild-type strain [NeuNAc-Galβ-GlcNAc-Galβ-Glcβ-Hep2(GlcNAc, Glcα) 3-deoxy-d-manno-2-octulosonic acid (KDO2)-lipid A; 1,4′ bisphosphorylated], although poorly adherent, rapidly invaded an epithelial cell layer in vitro, survived and multiplied early in blood, reached the cerebrospinal fluid, and caused lethal disease in the mouse model. In contrast, the Hep2(GlcNAc) KDO2-lipid A (pgm) mutant, which was highly adherent to cultured epithelial cells, caused significantly less bacteremia and mortality in the mouse model. The Hep2-KDO2-lipid A (rfaK) mutant was shown to be moderately adherent and to cause levels of bacteremia and mortality similar to those caused by the wild-type strain in the mouse model. The KDO2-lipid A (gmhB) mutant, which lacks the heptose disaccharide in the inner core of LOS, avidly attached to epithelial cells but was otherwise avirulent. Disease development correlated with expression of specific LOS structures and was associated with lower adherence but rapid meningococcal passage to and survival in the bloodstream, induction of proinflammatory cytokines, and the crossing of the blood-brain barrier. Taken together, the results of this study further define the importance of the LOS structure as a virulence component involved in multiple steps in the pathogenesis ofN. meningitidis.
Exchange of Lipooligosaccharide Synthesis Genes Creates Potential Guillain-Barré Syndrome-Inducible Strains ofCampylobacter jejuni
Authors: Phongsisay Vongsavanh , Perera Viraj N. , Fry Benjamin N. 
Published: January 2006

ABSTRACTHuman ganglioside-like structures, such as GM1, found on someCampylobacter jejunistrains have been linked to inducing the Guillain-Barré Syndrome (GBS). This study shows that aC. jejunistrain without GM1-like molecules acquired large DNA fragments, including lipooligosaccharide synthesis genes, from a strain expressing GM1-like molecules and consequently transformed into a number of potential GBS-inducible transformants, which exhibited a high degree of genetic and phenotypic diversity.
Reservoir Competency of Goats for the Ap-Variant 1 Strain of
Anaplasma phagocytophilum
Authors: Massung Robert F. , Mather Thomas N. , Levin Michael L. 
Published: January 2006

ABSTRACT

Field-collected ticks were used to infect goats with either Ap-ha, a strain associated with human disease, or a variant strain, Ap-Variant 1, of
Anaplasma phagocytophilum
. Goats were shown to be competent as a reservoir for Ap-Variant 1, and challenge and immunosuppression studies were used to further examine infection in the goat model.
Pathogen-Accelerated Atherosclerosis Occurs Early after Exposure and Can Be Prevented via Immunization
Authors: Miyamoto Takanari , Yumoto Hiromichi , Takahashi Yusuke , Davey Michael , Gibson Frank C. , Genco Caroline Attardo 
Published: January 2006

ABSTRACT

Here we report on early inflammatory events associated with
Porphyromonas gingivalis
-accelerated atherosclerosis in apolipoprotein E knockout (ApoE
−/−
) mice. Animals challenged with
P. gingivalis
presented with increased macrophage infiltration, innate immune marker expression, and atheroma without elevated systemic inflammatory mediators. This early local inflammatory response was prevented in mice immunized with
P. gingivalis
. We conclude that localized up-regulation of innate immune markers early after infection, rather than systemic inflammation, contributes to pathogen-accelerated atherosclerosis.
Calcium-Regulated Type III Secretion of Yop Proteins by an
Escherichia coli hha
Mutant Carrying a
Yersinia pestis
pCD1 Virulence Plasmid
Authors: Bartra Sara Schesser , Jackson Michael W. , Ross Julia A. , Plano Gregory V. 
Published: January 2006

ABSTRACT

A series of four large deletions that removed a total of ca. 36 kb of DNA from the ca. 70-kb
Yersinia pestis
pCD1 virulence plasmid were constructed using lambda Red-mediated recombination.
Escherichia coli hha
deletion mutants carrying the virulence plasmid with the deletions expressed a functional calcium-regulated type III secretion system. The
E. coli hha
/pCD1 system should facilitate molecular studies of the type III secretion process.
Role of Phase Variation of Type 1 Fimbriae in a Uropathogenic
Escherichia coli
Cystitis Isolate during Urinary Tract Infection
Authors: Snyder Jennifer A. , Lloyd Amanda L. , Lockatell C. Virginia , Johnson David E. , Mobley Harry L. T. 
Published: January 2006

ABSTRACT

Type 1 fimbrial phase-locked mutants of uropathogenic
Escherichia coli
cystitis isolate F11 were used to assess the role of the invertible element during urinary tract infection. Compared to the wild type, the phase-locked off mutant was attenuated, and constitutive production of type 1 fimbriae by the phase-locked on mutant did not provide a competitive advantage.
A DltA Mutant of
Haemophilus ducreyi
Is Partially Attenuated in Its Ability To Cause Pustules in Human Volunteers
Authors: Janowicz Diane , Leduc Isabelle , Fortney Kate R. , Katz Barry P. , Elkins Christopher , Spinola Stanley M. 
Published: January 2006

ABSTRACT

Haemophilus ducreyi
produces two outer membrane proteins, called DltA (
H. ducreyi
lectin A) and DsrA (
H. ducreyi
serum resistance A), that contribute to the ability of the organism to evade complement-mediated serum killing. In contrast to their isogenic parent strain, 35000HP, the DsrA mutant FX517 exhibits 0% survival in 50% normal human serum and the DltA mutant FX533 exhibits 23% survival. Compared to 35000HP, FX517 does not cause pustule formation in human volunteers. To test whether DltA was required for virulence in humans, seven volunteers were experimentally infected with 35000HP and FX533. Four subjects were inoculated with fixed doses of 35000HP (101 CFU or 130 CFU) at three sites on one arm and escalating doses of FX533 (range, 46 CFU to 915 CFU) at three sites on the other arm. Pustules only developed at mutant-injected sites at doses nearly twofold higher than that of the parent, suggesting that FX533 was partially attenuated. Three subjects were inoculated with similar doses of the parent (67 CFU) and mutant (104 CFU) at three sites. Pustules formed at five of nine parent sites and one of nine mutant sites. Overall, the papule and pustule formation rates for 35000HP and FX533 were similar for the trial. However, for the five subjects who received similar doses of the parent and mutant, pustules developed at 7 of 15 sites (46.7%; 95% confidence interval [CI], 16.9% to 76.5%) inoculated with the parent and at 1 of 15 (6.7%; 95% CI, 0.1% to 18.4%) sites inoculated with the mutant (
P
= 0.043). We concluded that the DltA mutant was attenuated in its ability to cause disease at doses similar to that of the parent.
Salmonella enterica
Serovar Typhimurium
ompS1
and
ompS2
Mutants Are Attenuated for Virulence in Mice
Authors: Rodríguez-Morales Olivia , Fernández-Mora Marcos , Hernández-Lucas Ismael , Vázquez Alejandra , Puente José Luis , Calva Edmundo 
Published: January 2006

ABSTRACT

Salmonella enterica
serovar Typhimurium mutants with mutations in the
ompS1
and
ompS2
genes, which code for quiescent porins, were nevertheless highly attenuated for virulence in a mouse model, indicating a role in pathogenesis. Similarly, a strain with a mutation in the gene coding for LeuO, a positive regulator of
ompS2
, was also attenuated.
Killed
Candida albicans
Yeasts and Hyphae Inhibit Gamma Interferon Release by Murine Natural Killer Cells
Authors: Murciano Celia , Villamón Eva , O'Connor José-Enrique , Gozalbo Daniel , Gil M. Luisa 
Published: January 2006

ABSTRACT

Killed yeasts and hyphae of
Candida albicans
inhibit gamma interferon secretion by highly purified murine NK cells in response to the Toll-like receptor ligands lipopolysaccharide and zymosan. This effect, which is also observed in the presence of NK-activating cytokines (interleukin-2 [IL-2], IL-12, and IL-15), may represent a novel mechanism of immune evasion that contributes to the virulence of
C. albicans
.
Human Tumor Necrosis Factor is a Chemoattractant for the ParasiteEntamoeba histolytica
Authors: Blazquez Samantha , Zimmer Christophe , Guigon Ghislaine , Olivo-Marin Jean-Christophe , Guillén Nancy , Labruyère Elisabeth 
Published: January 2006

ABSTRACTIn an analysis of the molecular factors triggering amebiasis, we investigated the chemotaxis ofEntamoeba histolyticatoward tumor necrosis factor (TNF) in vitro, using quantitative imaging techniques. Our findings enabled us to propose a hitherto unknown role for TNF as a chemokinetic and chemoattractant agent for this parasite.
Induction of In Vivo Antipolysaccharide Immunoglobulin Responses to IntactStreptococcus pneumoniaeIs More Heavily Dependent on Btk-Mediated B-Cell Receptor Signaling than Antiprotein Responses
Authors: Khan Abdul Q. , Sen Goutam , Guo Shuling , Witte Owen N. , Snapper Clifford M. 
Published: January 2006

ABSTRACTThe relative role of Btk-dependent B-cell receptor (BCR) signaling in the induction of antipolysaccharide (anti-PS) and antiprotein immunoglobulin (Ig) responses to an intact extracellular bacterium in vivo is unknown. Btklowmice exhibit reduced BCR signaling but largely restore B-cell development. Btklowmice immunized with intactStreptococcus pneumoniaeelicit reduced anti-PS but normal antiprotein Ig responses. Immunization of Btklowmice with PS-protein conjugate in saline results in an even more profound defect in the anti-PS but not antiprotein response, which is largely restored by use of a CpG-containing oligodeoxynucleotide as an adjuvant. These data demonstrate a greater dependence on Btk-mediated BCR signaling for physiologic anti-PS relative to antiprotein responses, as well as the existence of a compensatory Toll-like-receptor-mediated signaling pathway naturally triggered in response to intact bacterial pathogens.
Macrophages Isolated from Chickens Genetically Resistant or Susceptible to Systemic Salmonellosis Show Magnitudinal and Temporal Differential Expression of Cytokines and Chemokines following
Salmonella enterica
Challenge
Authors: Wigley Paul , Hulme Scott , Rothwell Lisa , Bumstead Nat , Kaiser Pete , Barrow Paul 
Published: January 2006

ABSTRACT

Macrophages from inbred chickens that are resistant to salmonellosis show greater and more rapid expression of proinflammatory chemokines and cytokines, including the key Th1-inducing cytokine interleukin-18, upon
Salmonella
challenge than those from susceptible birds. This suggests the possibility that salmonellosis resistant-line macrophages signal more effectively and rapidly and are more able to induce protective Th1 adaptive responses.
Upregulation of Immunoregulatory Src Homology 2 Molecule Containing Inositol Phosphatase and Mononuclear Cell Hyporesponsiveness in Oral Mucosa during Chronic Periodontitis
Authors: Muthukuru Manoj , Cutler Christopher W. 
Published: January 2006

ABSTRACT
Our group and others have shown in vitro that repeated exposure of human mononuclear cells (MNC) to lipopolysaccharide can induce endotoxin tolerance, evidenced by downregulation of TLR2 and TLR4 mRNA and surface protein; moreover, the ability of the MNC to secrete inflammatory cytokines is reduced. In situ studies performed on diseased and healthy gingiva suggest that a similar pattern of endotoxin tolerance occurs in human oral mucosa with chronic periodontitis (CP). We hypothesized that this represents a fundamental immunoregulatory mechanism to restore immune homeostasis and protect the host from further tissue damage. In the current study, we extend these published studies by providing evidence that Src homology 2 containing inositol phosphatase, an inhibitor of NF-κB activation and a negative regulator of the immune response, is upregulated in the oral mucosa during CP compared to its level during gingival health. We have also isolated MNC from patients with CP and those with healthy gingiva and show that MNC from CP subjects have a reduced capacity to upregulate TLR2, TLR4, and interleukin-1β in response to endotoxin. Thus, we provide more definitive evidence for a basic mechanism of immunoregulation in the oral mucosa.
Development of a Guinea Pig Immune Response-Related Microarray and Its Use To Define the Host Response followingMycobacterium bovisBCG Vaccination
Authors: Tree Julia A. , Elmore Michael J. , Javed Sajid , Williams Ann , Marsh Philip D. 
Published: January 2006

ABSTRACTImmune responses in the guinea pig model are understudied because of a lack of commercial reagents. We have developed a custom-made guinea pig oligonucleotide microarray (81 spots) and have examined the gene expression profile of splenocytes restimulated in vitro fromMycobacterium bovisBCG-vaccinated and naive animals. Eleven genes were significantly (P< 0.05) up-regulated following vaccination, indicating a Th1-type response. These results show that microarrays can be used to more fully define immune profiles of guinea pigs.
Analysis of the Function of EnteropathogenicEscherichia coliEspB by Random Mutagenesis
Authors: Luo Wensheng , Donnenberg Michael S. 
Published: January 2006

ABSTRACTEnteropathogenicEscherichia coli(EPEC) is an important cause of infantile diarrhea, especially in developing countries. EspB, a key virulence factor of EPEC, is required for the attaching and effacing effect characteristic of EPEC and enterohemorrhagicE. coliand has been posited to play several functions in the process of infection. Attaching and effacing activity is associated with the accumulation of filamentous actin beneath adherent bacteria as measured in the fluorescence actin staining (FAS) test. To determine whether different domains of EspB are responsible for different functions, 42 plasmids carrying mutatedespBwere introduced into anespBdeletion mutant. Two major groups ofespBmutants were identified. One group of 17 mutants exhibited positive FAS results and normal levels of hemolytic activity. Another group of 22 mutants exhibited negative FAS results and low levels of hemolytic activity. Three mutants were exceptional. One mutant was FAS positive but had significantly reduced hemolytic activity. Conversely, a second mutant was FAS negative but had full hemolytic activity. A third mutant had a significantly reduced FAS level compared to the wild type but full hemolytic activity. The results of EspF and Tir translocation assays confirmed that FAS-negative insertions disrupt effector translocation and mutants with FAS-positive insertions retain protein translocation activity. These results suggest that EspB has distinct domain functions involved in effector translocation that can be distinguished from its role as a component of the translocation pore.
Multifunctional Role of Choline Binding Protein G in Pneumococcal Pathogenesis
Authors: Mann B. , Orihuela C. , Antikainen J. , Gao G. , Sublett J. , Korhonen T. K. , Tuomanen E. 
Published: January 2006

ABSTRACT

Members of the choline binding protein (Cbp) family are noncovalently bound to phosphorylcholine residues on the surface of
Streptococcus pneumoniae
. It has been suggested that CbpG plays a role in adherence and increase virulence both at the mucosal surface and in the bloodstream, but the function of this protein has been unclear. A new sequence analysis indicated that CbpG is a possible member of the S1 family of multifunctional surface-associated serine proteases. Clinical isolates contained two alleles of
cbpG
, and one-third of the strains expressed a truncated protein lacking the C-terminal, cell wall-anchoring choline binding domain. CbpG on the surface of pneumococci (full length) or released into the supernatant (truncated) showed proteolytic activity for fibronectin and casein, as did CbpG expressed on lactobacilli or as a purified full-length or truncated recombinant protein. Recombinant CbpG (rCbpG)-coated beads adhered to eukaryotic cells, and TIGR4 mutants lacking CbpG or having a truncated CbpG protein showed decreased adherence in vitro and attenuation of disease in mouse challenge models of colonization, pneumonia, and bacteremia. Immunization with rCbpG was protective in an animal model of colonization and sepsis. We propose that CbpG is a multifunctional surface protein that in the cell-attached or secreted form cleaves host extracellular matrix and in the cell-attached form participates in bacterial adherence. This is the first example of distinct functions in virulence that are dependent on natural variation in expression of a choline binding domain.
NontypeableHaemophilus influenzaeAdheres to Intercellular Adhesion Molecule 1 (ICAM-1) on Respiratory Epithelial Cells and Upregulates ICAM-1 Expression
Authors: Avadhanula Vasanthi , Rodriguez Carina A. , Ulett Glen C. , Bakaletz Lauren O. , Adderson Elisabeth E. 
Published: January 2006

ABSTRACTNontypeableHaemophilus influenzae(NTHI) is an important respiratory pathogen. NTHI initiates infection by adhering to the airway epithelium. Here, we report that NTHI interacts with intracellular adhesion molecule 1 (ICAM-1) expressed by respiratory epithelial cells. A fourfold-higher number of NTHI bacteria adhered to Chinese hamster ovary (CHO) cells transfected with human ICAM-1 (CHO-ICAM-1) than to control CHO cells (P≤ 0.005). Blocking cell surface ICAM-1 with specific antibody reduced the adhesion of NTHI to A549 respiratory epithelial cells by 37% (P= 0.001) and to CHO-ICAM-1 cells by 69% (P= 0.005). Preincubating the bacteria with recombinant ICAM-1 reduced adhesion by 69% (P= 0.003). The adherence to CHO-ICAM-1 cells of NTHI strains deficient in the adhesins P5, P2, HMW1/2, and Hap or expressing a truncated lipooligosaccharide was compared to that of parental strains. Only strain 1128f−, which lacks the outer membrane protein (OMP) P5-homologous adhesin (P5 fimbriae), adhered less well than its parental strain. The numbers of NTHI cells adhering to CHO-ICAM-1 cells were reduced by 67% (P= 0.009) following preincubation with anti-P5 antisera. Furthermore, recombinant ICAM bound to an OMP preparation from strain 1128f+, which expresses P5, but not to that from its P5-deficient mutant, confirming a specific interaction between ICAM-1 and P5 fimbriae. Incubation of respiratory epithelial cells with NTHI increased ICAM-1 expression fourfold (P= 0.001). Adhesion of NTHI to the respiratory epithelium, therefore, upregulates the expression of its own receptor. Blocking interactions between NTHI P5 fimbriae and ICAM-1 may reduce respiratory colonization by NTHI and limit the frequency and severity of NTHI infection.
Characterization of Enteropathogenic
Escherichia coli
Mutants That Fail To Disrupt Host Cell Spreading and Attachment to Substratum
Authors: Nadler Chen , Shifrin Yulia , Nov Shani , Kobi Simi , Rosenshine Ilan 
Published: January 2006

ABSTRACT

Upon infection of host cells, enteropathogenic
Escherichia coli
(EPEC) delivers a set of effector proteins into the host cell cytoplasm via the type III secretion system (TTSS). The effectors subvert various host cell functions. We found that EPEC interferes with the spreading and ultimately with the attachment of suspended fibroblasts or epithelial cells, and we isolated mini-Tn
10
kan insertion mutants that failed to similarly affect host cells. In most mutants, the insertion sites were mapped to genes encoding TTSS components, including
cesD
,
escC
,
escJ
,
escV
,
espD
,
sepL
,
espB
, and
escF
. Other mutants contained insertions in
micC
or upstream of
bfpP
,
yehL
, or
ydeP
. The insertion upstream of
ydeP
was associated with a reduction in TTSS protein production and was studied further. To determine whether the apparent repression was due to constitutive expression of the downstream encoded genes,
ydeP
and
ydeO
expression vectors were constructed. Expression of recombinant YdeP, YdeO, or EvgA, a positive regulator of both
ydeP
and
ydeO
, repressed TTSS protein production. Our results suggest that upon activation of the EvgAS two-component system, EvgA (the response regulator) activates both
ydeP
and
ydeO
expression and that YdeP and YdeO act conjointly, directly or indirectly repressing expression of the TTSS genes.
Phospholipase A2Functions inPseudomonas aeruginosa- Induced Apoptosis
Authors: Kirschnek Susanne , Gulbins Erich 
Published: January 2006

ABSTRACTPseudomonas aeruginosa, a gram-negative, facultative pathogen, causes severe and often even lethal infections in immunocompromised patients, as well as cystic fibrosis patients. We show here that a variety ofP. aeruginosastrains activate phospholipase A2(PLA2), cultured epithelial cells, and fibroblasts, resulting in increased intracellular and extracellular arachidonic acid release. The use of different PLA2inhibitors revealed thatP. aeruginosa-induced arachidonic acid release is mediated by activation of cytosolic PLA2(cPLA2), whereas iPLA2or sPLA2do not seem to be involved in the response toP. aeruginosa. Likewise, the cPLA2-specific inhibitors MAFP and AACOCF3 prevented apoptosis of cultured epithelial cells uponP. aeruginosainfection, whereas inhibitors specific for iPLA2or sPLA2were without effect. The physiological significance of these findings is indicated by an inhibition of apoptosis in tracheal epithelial cells upon in vivo infection withP. aeruginosa. The data indicate that arachidonic acid generation by activation of cPLA2duringP. aeruginosainfection plays an important role in the induction of host cell death.
Deletion of the
Mycobacterium tuberculosis
α-Crystallin-Like
hspX
Gene Causes Increased Bacterial Growth In Vivo
Authors: Hu Yanmin , Movahedzadeh Farahnaz , Stoker Neil G. , Coates Anthony R. M. 
Published: January 2006

ABSTRACT

Hypervirulent mutants of
Mycobacterium tuberculosis
, whose growth rates are higher in vivo, have now been reported to have mutations in both regulatory and structural genes, but the basis for this unusual phenotype is not understood. One hypervirulence gene,
dosR
(
devR
, Rv2031c), activates transcription of approximately 50 genes in this pathogen in response to hypoxia and nitric oxide stress. The most dramatic activation (∼80-fold) is activation of the
hspX
(
acr
, Rv2031c) gene, which encodes a 16-kDa α-crystallin-like protein that is a major antigen. In this study we found that a Δ
acr
mutant exhibited increased growth following infection of BALB/c mice in vivo and in both resting and activated macrophages in vitro (as measured by the number of CFU). The increased growth in macrophages was equal to that of a Δ
dosR
mutant, while introduction of a constitutively expressed
hspX
gene reduced the Δ
dosR
virulence to wild-type levels. These results suggest that the increased number of CFU of the Δ
dosR
mutant was largely due to loss of
hspX
expression. We also confirmed that constitutive expression of
hspX
slows growth in vitro, and we propose that
hspX
plays an active role in slowing the growth of
M. tuberculosis
in vivo immediately following infection.