bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Neisseria meningitidis ZnuD Zinc Receptor Contributes to Interactions with Epithelial Cells and Supports Heme Utilization when Expressed in Escherichia coli
Authors: Kumar Pradeep , Sannigrahi Soma , Tzeng Yih-Ling 
Published: November 2011

ABSTRACT

Neisseria meningitidis
employs redundant heme acquisition mechanisms, including TonB receptor-dependent and receptor-independent uptakes. The TonB-dependent zinc receptor ZnuD shares significant sequence similarity to HumA, a heme receptor of
Moraxella catarrhalis
, and contains conserved motifs found in many heme utilization proteins. We present data showing that, when expressed in
Escherichia coli
, ZnuD allowed heme capture on the cell surface and supported the heme-dependent growth of an
E. coli hemA
strain. Heme agarose captured ZnuD in enriched outer membrane fractions, and this binding was inhibited by excess free heme, supporting ZnuD's specific interaction with heme. However, no heme utilization defect was detected in the meningococcal
znuD
mutant, likely due to unknown redundant TonB-independent heme uptake mechanisms. Meningococcal replication within epithelial cells requires a functional TonB, and we found that both the
znuD
and
tonB
mutants were defective not only in survival within epithelial cells but also in adherence to and invasion of epithelial cells. Ectopic complementation rescued these phenotypes. Interestingly, while
znuD
expression was repressed by Zur with zinc as a cofactor, it also was induced by iron in a Zur-independent manner. A specific interaction of meningococcal Fur protein with the
znuD
promoter was demonstrated by electrophoretic mobility shift assay (EMSA). Thus, the meningococcal ZnuD receptor likely participates in both zinc and heme acquisition, is regulated by both Zur and Fur, and is important for meningococcal interaction with epithelial cells.
Infection of Mice by Salmonella enterica Serovar Enteritidis Involves Additional Genes That Are Absent in the Genome of Serovar Typhimurium
Authors: Silva Cecilia A. , Blondel Carlos J. , Quezada Carolina P. , Porwollik Steffen , Andrews-Polymenis Helene L. , Toro Cecilia S. , Zaldívar Mercedes , Contreras Inés , McClelland Michael , Santiviago Carlos A. 
Published: November 2011

ABSTRACT

Salmonella enterica
serovar Enteritidis causes a systemic, typhoid-like infection in newly hatched poultry and mice. In the present study, a library of 54,000 transposon mutants of
S.
Enteritidis phage type 4 (PT4) strain P125109 was screened for mutants deficient in the
in vivo
colonization of the BALB/c mouse model using a microarray-based negative-selection screening. Mutants in genes known to contribute to systemic infection (e.g.,
Salmonella
pathogenicity island 2 [SPI-2],
aro
,
rfa
,
rfb
,
phoP
, and
phoQ
) and enteric infection (e.g., SPI-1 and SPI-5) in this and other
Salmonella
serovars displayed colonization defects in our assay. In addition, a strong attenuation was observed for mutants in genes and genomic islands that are not present in
S.
Typhimurium or in most other
Salmonella
serovars. These genes include a type I restriction/modification system (
SEN4290
to
SEN4292
), the
peg
fimbrial operon (
SEN2144A
to
SEN2145B
), a putative pathogenicity island (
SEN1970 to SEN1999
), and a type VI secretion system remnant
SEN1001
, encoding a hypothetical protein containing a lysin motif (LysM) domain associated with peptidoglycan binding. Proliferation defects for mutants in these individual genes and in exemplar genes for each of these clusters were confirmed in competitive infections with wild-type
S.
Enteritidis. A Δ
SEN1001
mutant was defective for survival within RAW264.7 murine macrophages
in vitro
. Complementation assays directly linked the
SEN1001
gene to phenotypes observed
in vivo
and
in vitro
. The genes identified here may perform novel virulence functions not characterized in previous
Salmonella
models.
Protection of Piglets against Edema Disease by Maternal Immunization with Stx2e Toxoid
Authors: Oanh Thi Kim Nguyen , Nguyen Viet Khong , De Greve Henri , Goddeeris Bruno Maria 
Published: November 2011

ABSTRACT

Edema disease (ED) in piglets is caused by Shiga toxin Stx2e-producing
Escherichia coli
. We show that a genetically disarmed Stx2e toxoid is a safe antigen that generates antiserum protecting piglets against the Stx2e toxin. Immunization of suckling piglets with the Stx2e toxoid was safe, had no adverse effects on growth of the piglets, and resulted in effective prevention of edema disease clinical symptoms after challenge with the Stx2e toxin. Our data showed that maternal immunity against the Stx2e toxoid can be transmitted from the vaccinated sows to the piglets via the colostrum. Very high levels of Stx2e-specific serum antibodies persisted in these piglets until 1 month postweaning, bridging the critical period in which the weaned piglets are most susceptible to edema infection. Challenge with Stx2e toxin resulted in clinical signs of edema disease and death of all control piglets from nonimmunized sows, whereas none of the piglets from immunized sows developed clinical signs of ED.
Immunobiotic Lactobacillus jensenii Elicits Anti-Inflammatory Activity in Porcine Intestinal Epithelial Cells by Modulating Negative Regulators of the Toll-Like Receptor Signaling Pathway
Authors: Shimazu Tomoyuki , Villena Julio , Tohno Masanori , Fujie Hitomi , Hosoya Shoichi , Shimosato Takeshi , Aso Hisashi , Suda Yoshihito , Kawai Yasushi , Saito Tadao , Makino Seiya , Ikegami Shuji , Itoh Hiroyuki , Kitazawa Haruki 
Published: November 2011

ABSTRACT

The effect of
Lactobacillus jensenii
TL2937 on the inflammatory immune response triggered by enterotoxigenic
Escherichia coli
(ETEC) and lipopolysaccharide (LPS) in a porcine intestinal epitheliocyte cell line (PIE cells) was evaluated. Challenges with ETEC or LPS elicited Toll-like receptor 4 (TLR4)-mediated inflammatory responses in cultured PIE cells, indicating that our cell line may be useful for studying inflammation in the guts of weaning piglets. In addition, we demonstrated that
L. jensenii
TL2937 attenuated the expression of proinflammatory cytokines and chemokines caused by ETEC or LPS challenge by downregulating TLR4-dependent nuclear factorκB (NF-κB) and mitogen-activated protein kinase (MAPK) activation. Furthermore, we demonstrated that
L. jensenii
TL2937 stimulation of PIE cells upregulated three negative regulators of TLRs: A20, Bcl-3, and MKP-1, deepening the understanding of an immunobiotic mechanism of action.
L. jensenii
TL2937-mediated induction of negative regulators of TLRs would have a substantial physiological impact on homeostasis in PIE cells, because excessive TLR inflammatory signaling would be downregulated. These results indicated that PIE cells can be used to study the mechanisms involved in the protective activity of immunobiotics against intestinal inflammatory damage and may provide useful information for the development of new immunologically functional feeds that help to prevent inflammatory intestinal disorders, including weaning-associated intestinal inflammation.
Mitogen-Activated Protein Kinase-Dependent Interleukin-1α Intracrine Signaling Is Modulated by YopP during Yersinia enterocolitica Infection
Authors: Bose Rumu , Thinwa Josephine , Chaparro Paola , Zhong Youmin , Bose Santanu , Zhong Guangming , Dube Peter H. 
Published: November 2011

ABSTRACTYersinia enterocoliticais a food-borne pathogen that preferentially infects the Peyer's patches and mesenteric lymph nodes, causing an acute inflammatory reaction. Even thoughY. enterocoliticainduces a robust inflammatory response during infection, the bacterium has evolved a number of virulence factors to limit the extent of this response. We previously demonstrated that interleukin-1α (IL-1α) was critical for the induction of gut inflammation characteristic ofY. enterocoliticainfection. More recently, the known actions of IL-1α are becoming more complex because IL-1α can function both as a proinflammatory cytokine and as a nuclear factor. In this study, we tested the ability ofY. enterocoliticato modulate intracellular IL-1α-dependent IL-8 production in epithelial cells. Nuclear translocation of pre-IL-1α protein and IL-1α-dependent secretion of IL-8 into the culture supernatant were increased during infection with a strain lacking the 70-kDa virulence plasmid compared to the case during infection with the wild type, suggesting thatYersiniaouter proteins (Yops) might be involved in modulating intracellular IL-1α signaling. Infection of HeLa cells with a strain lacking theyopPgene resulted in increased nuclear translocation of pre-IL-1α and IL-1α-dependent secretion of IL-8 similar to what is observed with bacteria lacking the virulence plasmid. YopP is a protein acetylase that inhibits mitogen-activated protein kinase (MAP kinase)- and NF-κB-dependent signal transduction pathways. Nuclear translocation of pre-IL-1α and IL-1α-dependent secretion of IL-8 in response toYersinia enterocoliticainfection were dependent on extracellular signal-regulated kinase (ERK) and p38 MAP kinase signaling but independent of NF-κB. These data suggest thatY. enterocoliticainhibits intracellular pre-IL-1α signaling and subsequent proinflammatory responses through inhibition of MAP kinase pathways.
The Enolase of Borrelia burgdorferi Is a Plasminogen Receptor Released in Outer Membrane Vesicles
Authors: Toledo A. , Coleman J. L. , Kuhlow C. J. , Crowley J. T. , Benach J. L. 
Published: November 2011

ABSTRACTThe agent of Lyme disease,Borrelia burgdorferi, has a number of outer membrane proteins that are differentially regulated during its life cycle. In addition to their physiological functions in the organism, these proteins also likely serve different functions in invasiveness and immune evasion. In borreliae, as well as in other bacteria, a number of membrane proteins have been implicated in binding plasminogen. The activation and transformation of plasminogen into its proteolytically active form, plasmin, enhances the ability of the bacteria to disseminate in the host. Outer membrane vesicles ofB. burgdorfericontain enolase, a glycolytic-cycle enzyme that catalyzes 2-phosphoglycerate to form phosphoenolpyruvate, which is also a known plasminogen receptor in Gram-positive bacteria. The enolase was cloned, expressed, purified, and used to generate rabbit antienolase serum. The enolase binds plasminogen in a lysine-dependent manner but not through ionic interactions. Although it is present in the outer membrane, microscopy and proteinase K treatment showed that enolase does not appear to be exposed on the surface. However, enolase in the outer membrane vesicles is accessible to proteolytic degradation by proteinase K. Samples from experimentally and tick-infected mice and rabbits as well as from Lyme disease patients exhibit recognition of enolase in serologic assays. Thus, this immunogenic plasminogen receptor released in outer membrane vesicles could be responsible for external proteolysis in the pericellular environment and have roles in nutrition and in enhancing dissemination.
Tissue Barriers of the Human Placenta to Infection with Toxoplasma gondii
Authors: Robbins Jennifer R. , Zeldovich Varvara B. , Poukchanski Anna , Boothroyd John C. , Bakardjiev Anna I. 
Published: November 2011

ABSTRACTToxoplasma gondiiis a ubiquitous, obligate intracellular parasite capable of crossing the placenta to cause spontaneous abortion, preterm labor, or significant disease in the surviving neonate. Exploration of the cellular and histological components of the placental barrier is in its infancy, and both how and whereT. gondiibreaches it are unknown. The human placenta presents two anatomical interfaces between maternal cells and fetal cells (trophoblasts): (i) the villous region where maternal blood bathes syncytialized trophoblasts for nutrient exchange and (ii) the maternal decidua, where mononuclear, extravillous trophoblasts anchor the villous region to the uterus. Using first-trimester human placental explants, we demonstrate that the latter site is significantly more vulnerable to infection, despite presenting a vastly smaller surface. This is consistent with past findings concerning two vertically transmitted viruses and one bacterium. We further explore whether three genetically distinctT. gondiitypes (I, II, and III) are capable of preferential placental infection and survival in this model. We find no difference in these strains' ability to infect placental explants; however, slightly slower growth is evident in type II (Prugniaud [Pru]) parasites relative to other cell types, although this did not quite achieve statistical significance.
The Acinetobacter baumannii Biofilm-Associated Protein Plays a Role in Adherence to Human Epithelial Cells
Authors: Brossard Kari A. , Campagnari Anthony A. 
Published: November 2011

ABSTRACT

Acinetobacter baumannii
is a significant source of nosocomial infections worldwide. This bacterium has the ability to survive and persist on multiple abiotic surfaces in health care facilities, and once a focus has been established, this opportunistic pathogen is difficult to eradicate. This paper demonstrates that the
A. baumannii
biofilm-associated protein (Bap) is necessary for mature biofilm formation on medically relevant surfaces, including polypropylene, polystyrene, and titanium. Scanning electron microscopy analyses of biofilms show that Bap is required for three-dimensional tower structure and water channel formation. In conjunction with persistence on abiotic surfaces, adherence to eukaryotic cells is an important step in bacterial colonization resulting in infection of the host. We have described Bap as the surface structure involved in adherence of
A. baumannii
to both normal human bronchial epithelial cells and normal human neonatal keratinocytes. However, Bap is not involved in internalization of the bacterium in these two cell lines. Furthermore, this study shows that the presence of Bap increases the bacterial cell surface hydrophobicity. The results of this study are pertinent, as the data lead to a better understanding of the role of Bap in biofilm formation on medical surfaces and in colonization of the host.
Novel Protein Substrates of the Phospho-Form Modification System in Neisseria gonorrhoeae and Their Connection to
O
-Linked Protein Glycosylation
Authors: Anonsen Jan Haug , Egge-Jacobsen Wolfgang , Aas Finn Erik , Børud Bente , Koomey Michael , Vik Åshild 
Published: November 2011

ABSTRACT

The zwitterionic phospho-form moieties phosphoethanolamine (PE) and phosphocholine (PC) are important components of bacterial membranes and cell surfaces. The major type IV pilus subunit protein of
Neisseria gonorrhoeae
, PilE, undergoes posttranslational modifications with these moieties via the activity of the pilin phospho-form transferase PptA. A number of observations relating to colocalization of phospho-form and
O
-linked glycan attachment sites in PilE suggested that these modifications might be either functionally or mechanistically linked or interact directly or indirectly. Moreover, it was unknown whether the phenomenon of phospho-form modification was solely dedicated to PilE or if other neisserial protein targets might exist. In light of these concerns, we screened for evidence of phospho-form modification on other membrane glycoproteins targeted by the broad-spectrum
O
-linked glycosylation system. In this way, two periplasmic lipoproteins, NGO1043 and NGO1237, were identified as substrates for PE addition. As seen previously for PilE, sites of PE modifications were clustered with those of glycan attachment. In the case of NGO1043, evidence for at least six serine phospho-form attachment sites was found, and further analyses revealed that at least two of these serines were also attachment sites for glycan. Finally, mutations altering glycosylation status led to the presence of
pptA
-dependent PC modifications on both proteins. Together, these results reinforce the associations established in PilE and provide evidence for dynamic interplay between phospho-form modification and
O
-linked glycosylation. The observations also suggest that phospho-form modifications likely contribute biologically at both intracellular and extracellular levels.
Communicating trends in resistance using a drug resistance index
Authors: Laxminarayan Ramanan , Klugman Keith P 
Published: November 2011

BackgroundAntibiotic resistance is a growing problem worldwide, but communicating this challenge to policymakers and non-experts is complicated by the multiplicity of bacterial pathogens and the distinct classes of antibiotics used to treat them. It is difficult, even for experts aware of the pharmacodynamics of antibiotics, to infer the seriousness of resistance without information on how commonly the antibiotic is being used and whether alternative antibiotics are available. Difficulty in aggregating resistance to multiple drugs to assess trends poses a further challenge to quantifying and communicating changes in resistance over time and across locations.MethodsWe developed a method for aggregating bacterial resistance to multiple antibiotics, creating an index comparable to the composite economic indices that measure consumer prices and stock market values. The resulting drug resistance index (DRI) and various subindices show antibiotic resistance and consumption trends in the USA but can be applied at any geographical level.FindingsThe DRI based on use patterns in 1999 forEscherichia colirose from 0.25 (95% CI 0.23 to 0.26) to 0.30 (95% CI 0.29 to 0.32) between 1999 and 2006. However, the adaptive DRI, which includes treatment of baseline resistant strains with alternative agents, climbed from 0.25 to 0.27 (95% CI 0.25 to 0.28) during that period. In contrast, both the static-use and the adaptive DRIs forAcinetobacterspp. rose from 0.41 (95% CI 0.4 to 0.42) to 0.48 (95% CI 0.46 to 0.49) between 1999 and 2006.InterpretationDivergence between the static-use and the adaptive-use DRIs forE colireflects the ability of physicians to adapt to increasing resistance. However, antibiotic use patterns did not change much in response to growing resistance toAcinetobacterspp. because physicians were unable to adapt; new drugs forAcinetobacterspp. are therefore needed. Composite indices that aggregate resistance to various drugs can be useful for assessing changes in drug resistance across time and space.
Primary and repeat surgical treatment for female pelvic organ prolapse and incontinence in parous women in the UK: a register linkage study
Authors: Abdel-fattah Mohamed , Familusi Akinbowale , Fielding Shona , Ford John , Bhattacharya Sohinee 
Published: November 2011

ObjectivesTo determine the lifetime risk of undergoing pelvic floor surgery in a cohort of UK parous women and the re-operation rates for pelvic floor surgery, time intervals for repeat surgery and independent risk factors for undergoing primary and repeat pelvic floor surgery.Study designA register linkage study.Main outcome measuresThe primary outcome was lifetime risk of parous women in the UK undergoing pelvic floor surgery for pelvic organ prolapse (POP), urinary incontinence (UI), and rectal prolapse or faecal incontinence (RP-FI). Secondary outcomes were re-operation rates and time interval of repeat surgery for POP/UI, and independent risk factors for undergoing primary and repeat pelvic floor surgery.Results34 631 women identified from the Aberdeen Maternity and Neonatal Database were linked with the Scottish Morbidity Records databases of NHS Scotland to assess relevant outcomes. The lifetime risk for women by age 80 years of undergoing any form of pelvic floor surgery was 12.2%. 2130 (6.2%) women had at least one pelvic floor surgery, of whom 407 (19%) had repeat operations. The median time intervals (IQR) between index and repeat UI and POP surgery were 2.80 (0.94–8.07) years and 3 (1.00–8.25) years, respectively. There is a reduced lifetime risk of pelvic floor surgery in women who had all deliveries by caesarean section (p<0.001) and those aged <20 years at first delivery (p=0.021). Women who sustained at least one perineal laceration (in the absence of a classified perineal tear) during delivery or who had at least one instrumental delivery with forceps use were at increased risk (p<0.001 and p=0.015, respectively).ConclusionsOur study shows that in the UK more than one in 10 parous women will require at least one surgical procedure for pelvic floor disorders over their lifetime. The study also identifies independent risk and protective factors for pelvic floor surgery in parous women.
Benchmarking the burden of 100 diseases: results of a nationwide representative survey within general practices
Authors: Grimaldi-Bensouda Lamiae , Begaud Bernard , Lert France , Rouillon Frederic , Massol Jacques , Guillemot Didier , Avouac Bernard , Duru Gerard , Magnier Anne-Marie , Rossignol Michel , Abenhaim Lucien ,   for the EPI3-LA-SER Group
Published: November 2011

ObjectiveTo assess the burden of diseases and quality of life (QOL) of patients for a large variety of diseases within general practice.DesignIn a representative nationwide cross-sectional study, a total of 825 general practitioners (GPs) were randomly selected from across France. Independent investigators recruited 8559 patients attending the GPs' practices. Data on QOL (12-Item Short Form questionnaire) and other individual characteristics were documented by the independent investigators for all participants in the waiting room. Medical information was recorded by GPs. Sampling was calibrated to national standards using the CALMAR (CALage sur MARges) weighting procedure. Associations of lower scores (ie, below vs above the first quartile) of physical and mental component scores (physical component summary score (PCS) and mental component summary score (MCS), respectively) with main diseases and patients characteristics were estimated using multivariate logistic regression. Weighted morbidity rates, PCS and MCS were computed for 100 diagnoses using the International Classification of Diseases (9th version).ResultsOverall mental impairment was observed among patients in primary care with an average MCS of 41.5 (SD 8.6), ranging from 33.0 for depressive disorders to 45.3 for patients exhibiting fractures or sprains. Musculoskeletal diseases were found to have the most pronounced effect on impaired physical health (OR=2.31; 95% CI 2.08 to 2.57) with the lowest PCS (45.6 (SD 8.8)) and ranked first (29.0%) among main diagnoses experienced by patients followed by cardiovascular diseases (26.7%) and psychological disorders (22.0%). When combining both prevalence and QOL, musculoskeletal diseases represented the heaviest burden in general practice.ConclusionsEtude épidémiologique de l'Impact de santé public sur 3 groupes de pathologies (EPI3) is the first study to provide reference figures for burden of disease in general practice across a wide range of morbidities, particularly valuable for health-economics and healthcare-system evaluation.