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mice repeatedly exposed to group-a β-haemolytic streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon.repeated exposure to group-a β-haemolytic streptococcus (gas) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. gas infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. here, we exposed developing sjl male mice to four injections with a gas homogenate and evaluated the following domains: motor coordination; genera ...201526304458
the impact of parental postpartum pertussis vaccination on infection in infants: a population-based study of cocooning in western australia.during a pertussis epidemic in 2011-2012 the western australian (wa) department of health implemented a 'cocooning' programme, offering free pertussis-containing vaccine (dtpa) to new parents. we assessed the impact of vaccinating parents with dtpa on the incidence of pertussis infection in newborns. births in wa during 2011-2012 were linked to a register of parental pertussis vaccinations and to notified reports of laboratory-proven pertussis in children <6 months of age. parents who received d ...201526320420
structural characterization and modeling of the borrelia burgdorferi hybrid histidine kinase hk1 periplasmic sensor: a system for sensing small molecules associated with tick feeding.two-component signal transduction systems are the primary mechanisms by which bacteria perceive and respond to changes in their environment. the hk1/rrp1 two-component system (tcs) in borrelia burgdorferi consists of a hybrid histidine kinase and a response regulator with diguanylate cyclase activity, respectively. phosphorylated rrp1 catalyzes the synthesis of c-di-gmp, a second messenger associated with bacterial life-style control networks. spirochetes lacking either hk1 or rrp1 are virulent ...201526321039
pertussis toxin exploits specific host cell signaling pathways for promoting invasion and translocation of escherichia coli k1 rs218 in human brain-derived microvascular endothelial cells.pertussis toxin (ptx), an ab5 toxin and major virulence factor of the whooping cough-causing pathogen bordetella pertussis, has been shown to affect the blood-brain barrier. dysfunction of the blood-brain barrier may facilitate penetration of bacterial pathogens into the brain, such as escherichia coli k1 (rs218). in this study, we investigated the influence of ptx on blood-brain barrier permissiveness to e. coli infection using human brain-derived endothelial hbmec and ty10 cells as in vitro mo ...201526324705
isolated cyaa-rtx subdomain from bordetella pertussis: structural and functional implications for its interaction with target erythrocyte membranes.the 126-kda bordetella pertussis cyaa-hemolysin (cyaa-hly) was previously expressed in escherichia coli as a soluble precursor that can be acylated to retain hemolytic activity. here, we investigated structural and functional characteristics of a ∼100-kda isolated rtx (repeat-in-toxin) subdomain (cyaa-rtx) of cyaa-hly. initially, we succeeded in producing a large amount with high purity of the his-tagged cyaa-rtx fragment and in establishing the interaction of acylated cyaa-hly with sheep red bl ...201526325465
suffer the infants: a severe case of pertussis in oregon, 2012.pertussis remains a public health concern in oregon, especially among young infants. the disease can be severe in this age group and is associated with a high inpatient cost. this report describes an oregon infant who was hospitalized with pertussis for 90 days, required extracorporeal oxygenation for 43 days, suffered complications including stroke, and had hospital charges totaling $1.5 million. pertussis morbidity among young infants argues for vaccination of women during each pregnancy and o ...201526327720
an ecological analysis of pertussis disease in minnesota, 2009-2013.the increase in pertussis cases in minnesota in the last decade has been mainly attributed to the switch from whole cell to acellular pertussis [as part of the diphtheria, tetanus and acellular pertussis vaccine (dtap)]. it is unclear, however, to what degree community-level risk factors also contribute. understanding these factors can help inform public health policy-makers about where else to target resources. we performed an ecological analysis within minnesota to identify risk factors at the ...201626330135
camp signalling of bordetella adenylate cyclase toxin through the shp-1 phosphatase activates the bimel-bax pro-apoptotic cascade in phagocytes.the adenylate cyclase toxin-hemolysin (cyaa, act or ac-hly) plays a key role in virulence of bordetella pertussis. cyaa penetrates myeloid cells expressing the complement receptor 3 (αm β2 integrin cd11b/cd18) and subverts bactericidal capacities of neutrophils and macrophages by catalysing unregulated conversion of cytosolic atp to the key signalling molecule adenosine 3',5'-cyclic monophosphate (camp). we show that the signalling of cyaa-produced camp hijacks, by an as yet unknown mechanism, t ...201626334669
brkautodisplay: functional display of multiple exogenous proteins on the surface of escherichia coli by using brka autotransporter.bacterial surface display technique enables the exogenous proteins or polypeptides displayed on the bacterial surface, while maintaining their relatively independent spatial structures and biological activities. the technique makes recombinant bacteria possess the expectant functions, subsequently, directly used for many applications. many proteins could be used to achieve bacterial surface display, among them, autotransporter, a member of the type v secretion system of gram-negative bacteria, h ...201526337099
pertussis in the era of new strains of bordetella pertussis.despite implementation of a successful vaccination program, pertussis remains a significant health problem. although the incidence of pertussis in the united states is reduced by approximately 80% compared with incidence before the introduction of vaccination in the 1940s, deaths still occur and the unrecognized disease burden remains high, with 1 million bordetella pertussis infections annually in the united states estimated by serologic surveys. reasons for the resurgence and current prevalenc ...201526337739
pertussis immunity and epidemiology: mode and duration of vaccine-induced immunity.the resurgence of pertussis in some countries that maintain high vaccination coverage has drawn attention to gaps in our understanding of the epidemiological effects of pertussis vaccines. in particular, major questions surround the nature, degree and durability of vaccine protection. to address these questions, we used mechanistic transmission models to examine regional time series incidence data from italy in the period immediately following the introduction of acellular pertussis (ap) vaccine ...201526337864
pertussis immunity and epidemiology: mode and duration of vaccine-induced immunity.the resurgence of pertussis in some countries that maintain high vaccination coverage has drawn attention to gaps in our understanding of the epidemiological effects of pertussis vaccines. in particular, major questions surround the nature, degree and durability of vaccine protection. to address these questions, we used mechanistic transmission models to examine regional time series incidence data from italy in the period immediately following the introduction of acellular pertussis (ap) vaccine ...201526337864
clinical characteristics of protracted bacterial bronchitis in chinese infants.protracted bacterial bronchitis (pbb) is the common cause of chronic cough in children worldwide, but its etiology has not been fully recognized in china. we retrospectively investigated a total of 66 hospitalized infants under the age of three years with chronic wet cough enrolled in the affiliated children's hospital of soochow university from october 2010 to march 2014. all patients underwent bronchoscopy and broncho-alveolar lavage (bal) samples were processed for microbiological and cytolog ...201526338462
whole-genome sequencing for tracing the transmission link between two ard outbreaks caused by a novel hadv serotype 7 variant, china.from december 2012 to february 2013, two outbreaks of acute respiratory disease caused by hadv-7 were reported in china. we investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (wgs) data. wgs analyses showed that the hadv-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated rna gene distinguished the outbreak isolates from other had ...201526338697
crystal structures of a double-barrelled fluoride ion channel.to contend with hazards posed by environmental fluoride, microorganisms export this anion through f(-)-specific ion channels of the fluc family. since the recent discovery of fluc channels, numerous idiosyncratic features of these proteins have been unearthed, including strong selectivity for f(-) over cl(-) and dual-topology dimeric assembly. to understand the chemical basis for f(-) permeation and how the antiparallel subunits convene to form a f(-)-selective pore, here we solve the crystal st ...201526344196
vaccine potentiation by combination adjuvants.adjuvants are crucial components of vaccines. they significantly improve vaccine efficacy by modulating, enhancing, or extending the immune response and at the same time reducing the amount of antigen needed. in contrast to previously licensed adjuvants, current successful adjuvant formulations often consist of several molecules, that when combined, act synergistically by activating a variety of immune mechanisms. these "combination adjuvants" are already registered with several vaccines, both i ...201426344621
therapeutic vaccine strategies against human papillomavirus.high-risk types of human papillomavirus (hpv) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. the transforming potential of hpvs is mediated by viral oncoproteins. these are essential for the induction and maintenance of the malignant phenotype. thus, hpv-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. therapeutic hpv vaccination is therefore an ideal scenario for proof-of-concept studies of canc ...201426344626
schistosome vaccine adjuvants in preclinical and clinical research.there is currently no vaccine available for human use for any parasitic infections, including the helminth disease, schistosomiasis. despite many researchers working towards this goal, one of the focuses has been on identifying new antigenic targets. the bar to achieve protective efficacy in humans was set at a consistent induction of 40% protection or better by the world health organisation (who), and although this is a modest goal, it is yet to be reached with the six most promising schistosom ...201426344751
choice and design of adjuvants for parenteral and mucosal vaccines.the existence of pathogens that escape recognition by specific vaccines, the need to improve existing vaccines and the increased availability of therapeutic (non-infectious disease) vaccines necessitate the rational development of novel vaccine concepts based on the induction of protective cell-mediated immune responses. for naive t-cell activation, several signals resulting from innate and adaptive interactions need to be integrated, and adjuvants may interfere with some or all of these signals ...201526344951
virus-induced secondary bacterial infection: a concise review.respiratory diseases are a very common source of morbidity and mortality among children. health care providers often face a dilemma when encountering a febrile infant or child with respiratory tract infection. the reason expressed by many clinicians is the trouble to confirm whether the fever is caused by a virus or a bacterium. the aim of this review is to update the current evidence on the virus-induced bacterial infection. we present several clinical as well in vitro studies that support the ...201526345407
adenylate cyclase toxin promotes bacterial internalisation into non phagocytic cells.bordetella pertussis causes whooping cough, a respiratory infectious disease that is the fifth largest cause of vaccine-preventable death in infants. though historically considered an extracellular pathogen, this bacterium has been detected both in vitro and in vivo inside phagocytic and non-phagocytic cells. however the precise mechanism used by b. pertussis for cell entry, or the putative bacterial factors involved, are not fully elucidated. here we find that adenylate cyclase toxin (act), one ...201526346097
roads to the development of improved pertussis vaccines paved by immunology.current acellular pertussis vaccines have various shortcomings, which may contribute to their suboptimal efficacy and waning immunity in vaccinated populations. this calls for the development of new pertussis vaccines capable of inducing long-lived protective immunity. immunization with whole cell pertussis vaccines and natural infection with bordetella pertussis induce distinct and more protective immune responses when compared with immunization with acellular pertussis vaccines. therefore, the ...201526347400
nk-dc crosstalk controls the autopathogenic th17 response through an innate ifn-γ-il-27 axis.ifn-γ is a pathogenic cytokine involved in inflammation. paradoxically, its deficiency exacerbates experimental autoimmune encephalomyelitis, uveitis, and arthritis. here, we demonstrate using ifn-γ(-/-) mice repleted with ifn-γ +/+: nk cells that innate production of ifn-γ from nk cells is necessary and sufficient to trigger an endogenous regulatory circuit that limits autoimmunity. after immunization, dcs recruited ifn-γ-producing nk cells to the draining lymph node and interacted with them in ...201526347474
human c1-inhibitor suppresses malaria parasite invasion and cytoadhesion via binding to parasite glycosylphosphatidylinositol and host cell receptors.plasmodium falciparum-induced severe malaria remains a continuing problem in areas of endemicity, with elevated morbidity and mortality. drugs targeting mechanisms involved in severe malaria pathology, including cytoadhesion of infected red blood cells (rbcs) to host receptors and production of proinflammatory cytokines, are still necessary. human c1-inhibitor (c1inh) is a multifunctional protease inhibitor that regulates coagulation, vascular permeability, and inflammation, with beneficial effe ...201526347576
human c1-inhibitor suppresses malaria parasite invasion and cytoadhesion via binding to parasite glycosylphosphatidylinositol and host cell receptors.plasmodium falciparum-induced severe malaria remains a continuing problem in areas of endemicity, with elevated morbidity and mortality. drugs targeting mechanisms involved in severe malaria pathology, including cytoadhesion of infected red blood cells (rbcs) to host receptors and production of proinflammatory cytokines, are still necessary. human c1-inhibitor (c1inh) is a multifunctional protease inhibitor that regulates coagulation, vascular permeability, and inflammation, with beneficial effe ...201526347576
ifn-γ induction by neutrophil-derived il-17a homodimer augments pulmonary antibacterial defense.the role of interleukin-17a (il-17a) in host defense against legionella pneumophila remains elusive. to address this issue, we used il17a(-/-), il17f(-/-), and il17a/il17f(-/-) mice on a c57bl/6 (non-permissive) background and il-17 neutralizing abs in mice on an a/j (permissive) background. higher bacterial (l. pneumophila) counts in the lung and blood along with reduced neutrophil recruitment were detected in il17a(-/-), but not il17f(-/-), mice. we found that neutrophils produce il-17a homodi ...201526349661
ifn-γ induction by neutrophil-derived il-17a homodimer augments pulmonary antibacterial defense.the role of interleukin-17a (il-17a) in host defense against legionella pneumophila remains elusive. to address this issue, we used il17a(-/-), il17f(-/-), and il17a/il17f(-/-) mice on a c57bl/6 (non-permissive) background and il-17 neutralizing abs in mice on an a/j (permissive) background. higher bacterial (l. pneumophila) counts in the lung and blood along with reduced neutrophil recruitment were detected in il17a(-/-), but not il17f(-/-), mice. we found that neutrophils produce il-17a homodi ...201526349661
sequential unfolding of the hemolysin two-partner secretion domain from proteus mirabilis.protein secretion is a major contributor to gram-negative bacterial virulence. type vb or two-partner secretion (tps) pathways utilize a membrane bound β-barrel b component (tpsb) to translocate large and predominantly virulent exoproteins (tpsa) through a nucleotide independent mechanism. we focused our studies on a truncated tpsa member termed hemolysin a (hpma265), a structurally and functionally characterized tps domain from proteus mirabilis. contrary to the expectation that the tps domain ...201526350294
adhesins involved in attachment to abiotic surfaces by gram-negative bacteria.during the first step of biofilm formation, initial attachment is dictated by physicochemical and electrostatic interactions between the surface and the bacterial envelope. depending on the nature of these interactions, attachment can be transient or permanent. to achieve irreversible attachment, bacterial cells have developed a series of surface adhesins promoting specific or nonspecific adhesion under various environmental conditions. this article reviews the recent advances in our understandi ...201526350310
inhibition of ltxa toxicity by blocking cholesterol binding with peptides.the leukotoxin (ltxa) produced by aggregatibacter actinomycetemcomitans kills host immune cells, allowing the bacterium to establish an ecological niche in the upper aerodigestive tract of its human host. the interaction of ltxa with human immune cells is both complex and multifaceted, involving membrane lipids as well as cell-surface proteins. in the initial encounter with the host cell, ltxa associates with lymphocyte function-associated antigen-1, a cell surface adhesion glycoprotein. however ...201526352738
inhibition of ltxa toxicity by blocking cholesterol binding with peptides.the leukotoxin (ltxa) produced by aggregatibacter actinomycetemcomitans kills host immune cells, allowing the bacterium to establish an ecological niche in the upper aerodigestive tract of its human host. the interaction of ltxa with human immune cells is both complex and multifaceted, involving membrane lipids as well as cell-surface proteins. in the initial encounter with the host cell, ltxa associates with lymphocyte function-associated antigen-1, a cell surface adhesion glycoprotein. however ...201526352738
laboratory diagnosis of pertussis.the introduction of vaccination in the 1950s significantly reduced the morbidity and mortality of pertussis. however, since the 1990s, a resurgence of pertussis has been observed in vaccinated populations, and a number of causes have been proposed for this phenomenon, including improved diagnostics, increased awareness, waning immunity, and pathogen adaptation. the resurgence of pertussis highlights the importance of standardized, sensitive, and specific laboratory diagnoses, the lack of which i ...201526354823
draft genome sequence of a bordetella pertussis strain with the virulence-associated allelic variant ptxp3, isolated in italy.despite a universal immunization program, pertussis has persisted and resurged, and is of particular concern for infants in terms of morbidity and mortality. here, we report the genome sequence of a bordetella pertussis strain with the virulence-associated allelic variant ptxp3, isolated from a 45-day-old infant.201526358588
structural and functional studies of the pseudomonas aeruginosa minor pilin, pile.many bacterial pathogens, including pseudomonas aeruginosa, use type iva pili (t4ap) for attachment and twitching motility. t4ap are composed primarily of major pilin subunits, which are repeatedly assembled and disassembled to mediate function. a group of pilin-like proteins, the minor pilins fimu and pilvwxe, prime pilus assembly and are incorporated into the pilus. we showed previously that minor pilin pile depends on the putative priming subcomplex pilvwx and the non-pilin protein pily1 for ...201526359492
functional importance of the gly cluster in transmembrane helix 2 of the bordetella pertussis cyaa-hemolysin: implications for toxin oligomerization and pore formation.adenylate cyclase-hemolysin (cyaa) is a major virulence factor of bordetella pertussis causing whooping cough in humans. we previously showed that two transmembrane helices (α2 and α3) in the hemolysin domain (cyaa-hly) are crucially involved in hemolytic activity. here, pcr-based substitutions were employed to investigate a potential involvement in hemolysis of a series of four gly residues (gly(530), gly(533), gly(537) and gly(544)) which map onto one face of a helical wheel plot of pore-linin ...201526363293
development of real-time pcr assays for the detection of moraxella macacae associated with bloody nose syndrome in rhesus (macaca mulatta) and cynomolgus (macaca fascicularis) macaques.moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. the aim of this study was to develop specific molecular diagnostic assays for m. macacae and to determine their performance characteristics.201526365904
surfactant protein d binds to coxiella burnetii and results in a decrease in interactions with murine alveolar macrophages.coxiella burnetii is a gram-negative, obligate intracellular bacterium and the causative agent of q fever. infections are usually acquired after inhalation of contaminated particles, where c. burnetii infects its cellular target cells, alveolar macrophages. respiratory pathogens encounter the c-type lectin surfactant protein d (sp-d) during the course of natural infection. sp-d is a component of the innate immune response in the lungs and other mucosal surfaces. many gram-negative pulmonary path ...201526366725
clinical and molecular epidemiology of human rhinovirus infections in patients with hematologic malignancy.human rhinoviruses (hrvs) are common causes of upper respiratory tract infection (urti) in hematologic malignancy (hm) patients. predictors of lower respiratory tract infection (lrti) including the impact of hrv species and types are poorly understood.201526370315
type iii secretion systems: the bacterial flagellum and the injectisome.the flagellum and the injectisome are two of the most complex and fascinating bacterial nanomachines. at their core, they share a type iii secretion system (t3ss), a transmembrane export complex that forms the extracellular appendages, the flagellar filament and the injectisome needle. recent advances, combining structural biology, cryo-electron tomography, molecular genetics, in vivo imaging, bioinformatics and biophysics, have greatly increased our understanding of the t3ss, especially the str ...201526370933
the bacterial divisome: ready for its close-up.bacterial cells divide by targeting a transmembrane protein machine to the division site and regulating its assembly and disassembly so that cytokinesis occurs at the correct time in the cell cycle. the structure and dynamics of this machine (divisome) in bacterial model systems are coming more clearly into focus, thanks to incisive cell biology methods in combination with biochemical and genetic approaches. the main conserved structural element of the machine is the tubulin homologue ftsz, whic ...201526370940
outer membrane lipoprotein biogenesis: lol is not the end.bacterial lipoproteins are lipid-anchored proteins that contain acyl groups covalently attached to the n-terminal cysteine residue of the mature protein. lipoproteins are synthesized in precursor form with an n-terminal signal sequence (ss) that targets translocation across the cytoplasmic or inner membrane (im). lipid modification and ss processing take place at the periplasmic face of the im. outer membrane (om) lipoproteins take the localization of lipoproteins (lol) export pathway, which end ...201526370942
interspecies variations in bordetella catecholamine receptor gene regulation and function.bordetella bronchiseptica can use catecholamines to obtain iron from transferrin and lactoferrin via uptake pathways involving the bfra, bfrd, and bfre outer membrane receptor proteins, and although bordetella pertussis has the bfrd and bfre genes, the role of these genes in iron uptake has not been demonstrated. in this study, the bfrd and bfre genes of b. pertussis were shown to be functional in b. bronchiseptica, but neither b. bronchiseptica bfrd nor bfre imparted catecholamine utilization t ...201526371128
waning and aging of cellular immunity to bordetella pertussis.while it is clear that the maintenance of bordetella pertussis-specific immunity evoked both after vaccination and infection is insufficient, it is unknown at which pace waning occurs and which threshold levels of sustained functional memory b and t cells are required to provide long-term protection. longevity of human cellular immunity to b. pertussis has been studied less extensively than serology, but is suggested to be key for the observed differences between the duration of protection induc ...201526371178
abundant toxin-related genes in the genomes of beneficial symbionts from deep-sea hydrothermal vent mussels.bathymodiolus mussels live in symbiosis with intracellular sulfur-oxidizing (sox) bacteria that provide them with nutrition. we sequenced the sox symbiont genomes from two bathymodiolus species. comparison of these symbiont genomes with those of their closest relatives revealed that the symbionts have undergone genome rearrangements, and up to 35% of their genes may have been acquired by horizontal gene transfer. many of the genes specific to the symbionts were homologs of virulence genes. we di ...201526371554
bordetella pertussis transmission.bordetella pertussis and b. bronchiseptica are gram-negative bacterial respiratory pathogens. bordetella pertussis is the causative agent of whooping cough and is considered a human-adapted variant of b. bronchiseptica. bordetella pertussis and b. bronchiseptica share mechanisms of pathogenesis and are genetically closely related. however, despite the close genetic relatedness, these bordetella species differ in several classic fundamental aspects of bacterial pathogens such as host range, patho ...201526374235
structural models of intrinsically disordered and calcium-bound folded states of a protein adapted for secretion.many gram-negative bacteria use type i secretion systems, t1ss, to secrete virulence factors that contain calcium-binding repeat-in-toxin (rtx) motifs. here, we present structural models of an rtx protein, rd, in both its intrinsically disordered calcium-free apo-state and its folded calcium-bound holo-state. apo-rd behaves as a disordered polymer chain comprising several statistical elements that exhibit local rigidity with residual secondary structure. holo-rd is a folded multi-domain protein ...201526374675
single amino acid polymorphisms of pertussis toxin subunit s2 (ptxb) affect protein function.whooping cough due to bordetella pertussis is increasing in incidence, in part due to accumulation of mutations which increase bacterial fitness in highly vaccinated populations. polymorphisms in the pertussis toxin, ptxa and ptxb genes, and the pertactin, prn genes of clinical isolates of bordetella pertussis collected in cincinnati from 1989 through 2005 were examined. while the ptxa and prn genotypes were variable, all 48 strains had the ptxb2 genotype; ptxb1 encodes glycine at amino acid 18 ...201526375454
identification of a novel human papillomavirus, type hpv199, isolated from a nasopharynx and anal canal, and complete genomic characterization of papillomavirus species gamma-12.the novel human papillomavirus type 199 (hpv199) was initially identified in a nasopharyngeal swab sample obtained from a 25 year-old immunocompetent male. the complete genome of hpv199 is 7,184 bp in length with a gc content of 36.5%. comparative genomic characterization of hpv199 and its closest relatives showed the classical genomic organization of gammapapillomaviruses (gamma-pvs). hpv199 has seven major open reading frames (orfs), encoding five early (e1, e2, e4, e6, and e7) and two late (l ...201526375679
interdomain contacts and the stability of serralysin protease from serratia marcescens.the serralysin family of bacterial metalloproteases is associated with virulence in multiple modes of infection. these extracellular proteases are members of the repeats-in-toxin (rtx) family of toxins and virulence factors, which mediated virulence in e. coli, b. pertussis, and p. aeruginosa, as well as other animal and plant pathogens. the serralysin proteases are structurally dynamic and their folding is regulated by calcium binding to a c-terminal domain that defines the rtx family of protei ...201526378460
evidence for infection and inflammation in infant deaths in a country with historically low incidences of sudden infant death syndrome.total infant mortality in hungary has been higher than other european countries; however, the reported incidence of sudden infant death syndrome (sids) has been lower. the low incidence of sids in hungary has been supported by evidence obtained from the high rate of scene of death investigation and medico-legal autopsy mandatory since the 1950s. in this study, we compared the incidence of explained and unexplained infant deaths in hungary for three periods: 1979-1989 when the incidence of sids w ...201526379661
changes in clinical presentation and epidemiology of respiratory pathogens associated with acute respiratory illness in military trainees after reintroduction of adenovirus vaccine.background.  adenovirus (ad) has long been the predominant cause of acute respiratory illness (ari) in military trainees. in 2011, live oral ad vaccines for serotypes 4 and 7 were reintroduced into us basic military training populations. this study evaluated the impact on clinical presentations and other respiratory pathogens. methods.  the center for advanced molecular detection at joint base san antonio-lackland prospectively collects demographic, clinical, and polymerase chain reaction data f ...201526380351
latent class analysis of diagnostic tests for adenovirus, bordetella pertussis and influenza virus infections in german adults with longer lasting coughs.laboratory tests in adult outpatients with longer lasting coughs to identify a potential causal pathogen are rarely performed, and there is no gold standard for these diagnostic tests. while the diagnostic validity of serological tests for pertussis is well established their potential contribution for diagnosing adenovirus and influenza virus a and b infections is unclear. a sentinel study into the population-based incidence of longer lasting coughs in adults was done in rostock (former east ger ...201626380914
mapping type iv secretion signals on the primase encoded by the broad-host-range plasmid r1162 (rsf1010).the plasmid r1162 (rsf1010) encodes a primase essential for its replication. this primase makes up the c-terminal part of moba, a multifunctional protein with the relaxase as a separate n-terminal domain. the primase is also translated separately as the protein repb'. here, we map two signals for type iv secretion onto the recently solved structure of repb'. one signal is located internally within repb' and consists of a long α-helix and an adjacent disordered region rich in arginines. the secon ...201526381189
the bordetella adenylate cyclase repeat-in-toxin (rtx) domain is immunodominant and elicits neutralizing antibodies. 201526386047
heterogeneity of pulmonary endothelial cyclic nucleotide response to pseudomonas aeruginosa exoy infection.here, we tested the hypothesis that a promiscuous bacterial cyclase synthesizes purine and pyrimidine cyclic nucleotides in the pulmonary endothelium. to test this hypothesis, pulmonary endothelial cells were infected with a strain of the gram-negative bacterium pseudomonas aeruginosa that introduces only exoenzyme y (pa103 δexouexot::tc pucpexoy; exoy(+)) via a type iii secretion system. purine and pyrimidine cyclic nucleotides were simultaneously detected using mass spectrometry. pulmonary art ...201526386118
pertussis in children in the istanbul faculty of medicine: results for four years.we investigated the frequency of pertussis among children in the istanbul faculty of medicine hospital during a period of four years. clinical specimens were obtained from children who exhibited symptoms of whooping cough; a portion of the cases were confirmed microbiologically by pcr as pertussis. a total of 410 nasopharyngeal aspirates were taken for detection of bordetella pertussis/parapertussis. the age groups of the patients were 0-4 months (n=201), >4 -12 months (n=49), 1-4 years (n=79), ...201526388594
a newborn with pertussis accompanying nephrotic syndrome.pertussis or whooping cough is a vaccine-preventable disease that still remains a serious infection in neonates and young infants. the disease is particularly severe in infants less than three months old, who are often infected by their parents. congenital nephrotic syndrome is a rare entity presenting within the first three months. it encompasses a heterogeneous group of entities with genetic, infectious and idiopathic etiologies. in this report we describe a newborn infant who presented with c ...201526388601
new data on vaccine antigen deficient bordetella pertussis isolates.evolution of bordetella pertussis is driven by natural and vaccine pressures. isolates circulating in regions with high vaccination coverage present multiple allelic and antigenic variations as compared to isolates collected before introduction of vaccination. furthermore, during the last epidemics reported in regions using pertussis acellular vaccines, isolates deficient for vaccine antigens, such as pertactin (prn), were reported to reach high proportions of circulating isolates. more sporadic ...201526389958
bordetella adenylate cyclase toxin: a unique combination of a pore-forming moiety with a cell-invading adenylate cyclase enzyme.the adenylate cyclase toxin-hemolysin (cyaa, act or ac-hly) is a key virulence factor of the whooping cough agent bordetella pertussis. cyaa targets myeloid phagocytes expressing the complement receptor 3 (cr3, known as αmβ2 integrin cd11b/cd18 or mac-1) and translocates by a poorly understood mechanism directly across the cytoplasmic membrane into cell cytosol of phagocytes an adenylyl cyclase(ac) enzyme. this binds intracellular calmodulin and catalyzes unregulated conversion of cytosolic atp ...201526391732
a limit to the divergent allele advantage model supported by variable pathogen recognition across hla-drb1 allele lineages.genetic diversity in human leukocyte antigen (hla) molecules is thought to have arisen from the co-evolution between host and pathogen and maintained by balancing selection. heterozygote advantage is a common proposed scenario for maintaining high levels of diversity in hla genes, and extending from this, the divergent allele advantage (daa) model suggests that individuals with more divergent hla alleles bind and recognize a wider array of antigens. while the daa model seems biologically suitabl ...201526392055
contribution of pertussis toxin to the pathogenesis of pertussis disease.pertussis toxin (pt) is a multisubunit protein toxin secreted by bordetella pertussis, the bacterial agent of the disease pertussis or whooping cough. pt in detoxified form is a component of all licensed acellular pertussis vaccines, since it is considered to be an important virulence factor for this pathogen. pt inhibits g protein-coupled receptor signaling through gi proteins in mammalian cells, an activity that has led to its widespread use as a cell biology tool. but how does this activity o ...201526394801
novel therapies for the treatment of pertussis disease.whooping cough, or pertussis, incidence has reached levels not seen since the 1950s. previous studies have shown that antibiotics fail to improve the course of disease unless diagnosed early. early diagnosis is complicated by the non-diagnostic presentation of disease early in infection. this review focuses on previous attempts at developing novel host-directed therapies for the treatment of pertussis. in addition, two novel approaches from our group are discussed. manipulation of the signaling ...201526394802
isolation of high level macrolide resistant bordetella pertussis without transition mutation at domain v in iran.bordetella pertussis, as a causative agent of whooping cough, due to the annual rise y of infection cases, failure of prophylaxis and treatment by macrolides, is considered as the new concern in the health care system.201526396713
deciphering the mystery of hepatitis b virus receptors: a historical perspective.hepatitis b virus is one of the major reasons of viral hepatitis with an estimated 350 million infected patients worldwide. although, the virus was discovered and cloned more than three decades ago, its entry mechanism has still been in investigation. numerous potential candidates have been proposed and investigated rigorously to reveal hbv entry mechanism and to unveil the first door of viral entry to hepatocytes. this review provides a short account of role of receptors for entry of hbv into h ...201526396975
communicable diseases prioritized according to their public health relevance, sweden, 2013.to establish strategic priorities for the public health agency of sweden we prioritized pathogens according to their public health relevance in sweden in order to guide resource allocation. we then compared the outcome to ongoing surveillance. we used a modified prioritization method developed at the robert koch institute in germany. in a delphi process experts scored pathogens according to ten variables. we ranked the pathogens according to the total score and divided them into four priority gr ...201526397699
[bordetella pertussis lipooligosaccharide-derived neoglycoconjugates - new components of pertussis vaccine].pertussis is a contagious respiratory tract disease caused by the gram-negative bacterium bordetella pertussis. despite widespread vaccination, in recent years the pertussis incidence has increased. the whole-cell pertussis vaccine has been very effective but reactogenic. therefore the improved vaccines contain only a few isolated and inactivated antigens of b. pertussis. however, a waning of the acellular vaccine-induced immunity indicates that these vaccines lack some important protective b. p ...201526400888
variation in bordetella pertussis susceptibility to erythromycin and virulence-related genotype changes in china (1970-2014).to investigate changes in virulence-related genotypes and in the antimicrobial susceptibility of bordetella pertussis isolates collected from the 1970s to 2014 in the northern part of china.201526406905
genetic diversity and population dynamics of bordetella pertussis in china between 1950-2007.pertussis is an acute respiratory infectious disease caused by the bacterium bordetella pertussis. although pertussis vaccination was introduced in the 1960s, pertussis is still an endemic disease in china. to better understand the genetic diversity of the chinese b. pertussis population, we characterized 115 clinical isolates obtained in china during 1950-2007 using multilocus variable-number tandem repeat analysis (mlva). forty-six different b. pertussis mlva profiles (mts) were identified, of ...201526409140
prevalence, diagnosis, and disease course of pertussis in adults with acute cough: a prospective, observational study in primary care.most cases of adult pertussis probably remain undiagnosed.201526412843
the first report of epidemic pertussis by bahaodowle razi from the 15th century anno domini.pertussis or "whooping cough" is an acute, communicable infection of the respiratory tract caused by the gram-negative bacterium bordetella pertussis. it has been recorded in history of medicine that the first pertussis epidemic was reported in 1578 by a french scientist, guillaume de baillou, in paris. furthermore, the causative agent was first isolated in 1906 by jules jean baptiste vincent bordet and his brother-in-law octave gengou. however, it seems that earlier reports can be found in hist ...201526413316
bordetella filamentous hemagglutinin and fimbriae: critical adhesins with unrealized vaccine potential.pertussis, or whooping cough, is a highly contagious respiratory disease that is caused by the gram-negative bacterium bordetella pertussis, which is transmitted exclusively from human to human. while vaccination against b. pertussis has been successful, replacement of the whole cell vaccine with an acellular component vaccine has correlated with reemergence of the disease, especially in adolescents and infants. based on their presumed importance in mediating adherence to host tissues, filamento ...201526416077
the sugar kinase that is necessary for the catabolism of rhamnose in rhizobium leguminosarum directly interacts with the abc transporter necessary for rhamnose transport.rhamnose catabolism in rhizobium leguminosarum was found to be necessary for the ability of the organism to compete for nodule occupancy. characterization of the locus necessary for the catabolism of rhamnose showed that the transport of rhamnose was dependent upon a carbohydrate uptake transporter 2 (cut2) abc transporter encoded by rhastpq and on the presence of rhak, a protein known to have sugar kinase activity. a linker-scanning mutagenesis analysis of rhak showed that the kinase and transp ...201526416834
interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis.ectopic lymphoid-like structures (elss) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. through evaluation of synovial tissues from rheumatoid arthritis (ra) patients, we now show that low interleukin-27 (il-27) expression corresponds with an increased incidence of els and gene signatures associated with their development and activity. the presence of synovial els was also noted in mice deficient in the i ...201526417004
the bidirectional relationship between sleep and immunity against infections.sleep is considered an important modulator of the immune response. thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. for instance, shorter sleep durations are associated with a rise in suffering from the common cold. the function of sleep in altering immune responses must be determined to understand how sleep deprivation increases the susceptibility to viral, bacterial, and parasitic infections. there are several explanations for greater susceptibility t ...201526417606
biological and pharmacological aspects of the nk1-receptor.the neurokinin 1 receptor (nk-1r) is the main receptor for the tachykinin family of peptides. substance p (sp) is the major mammalian ligand and the one with the highest affinity. sp is associated with multiple processes: hematopoiesis, wound healing, microvasculature permeability, neurogenic inflammation, leukocyte trafficking, and cell survival. it is also considered a mitogen, and it has been associated with tumorigenesis and metastasis. tachykinins and their receptors are widely expressed in ...201526421291
role of atypical pathogens and the antibiotic prescription pattern in acute bronchitis: a multicenter study in korea.the role of atypical bacteria and the effect of antibiotic treatments in acute bronchitis are still not clear. this study was conducted at 22 hospitals (17 primary care clinics and 5 university hospitals) in korea. outpatients (aged ≥ 18 yr) who had an acute illness with a new cough and sputum (≤ 30 days) were enrolled in 2013. multiplex real-time polymerase chain reaction (rt-pcr) was used to detect five atypical bacteria. a total of 435 patients were diagnosed as having acute bronchitis (vs. p ...201526425041
an in vitro assay for substrate translocation by fhac in liposomes.the two-partner secretion (tps) pathway is used by gram-negative bacteria to secrete a large family of virulence exoproteins. its name is derived from the fact that it involves two proteins, a secreted tpsa protein and a cognate tpsb transporter in the outer membrane. a typical tps system is represented by the filamentous hemagglutinin fhab (tpsa protein) and its transporter fhac (tpsb protein) of bordetella pertussis. results from mutational analysis and heterologous expression experiments sugg ...201526427679
review of the neutrophil response to bordetella pertussis infection.the nature and timing of the neutrophil response to infection with bordetella pertussis is influenced by multiple virulence factors expressed by the bacterium. after inoculation of the host airway, the recruitment of neutrophils signaled by b. pertussis lipooligosaccharide (los) is suppressed by pertussis toxin (ptx). over the next week, the combined activities of ptx, los and adenylate cyclase toxin (act) result in production of cytokines that generate an il-17 response, promoting neutrophil re ...201526432818
pertactin negative bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model.whooping cough or pertussis is a highly infectious respiratory disease in humans caused by bordetella pertussis. the use of acellular vaccines (acv) has been associated with the recent resurgence of pertussis in developed countries including australia despite high vaccination coverage where b. pertussis strains that do not express pertactin (prn), a key antigenic component of the acv, have emerged and become prevalent. in this study, we used an in vivo competition assay in mice immunised with ac ...201526432908
a rare case of diffuse alveolar hemorrhage secondary to acute pulmonary histoplasmosis.diffuse alveolar hemorrhage (dah) is a rare presentation of acute pulmonary histoplasmosis. while histoplasmosis has been reported to cause hemoptysis and alveolar hemorrhage in children, the english language literature lacks any adult case reports documenting this association. we report a case of pulmonary histoplasmosis where the initial presentation was pneumonia with a subsequent diagnosis of dah.201526435863
pore-formation by adenylate cyclase toxoid activates dendritic cells to prime cd8+ and cd4+ t cells.the adenylate cyclase toxin-hemolysin (cyaa) of bordetella pertussis is a bi-functional leukotoxin. it penetrates myeloid phagocytes expressing the complement receptor 3 and delivers into their cytosol its n-terminal adenylate cyclase enzyme domain (~400 residues). in parallel, ~1300 residue-long rtx hemolysin moiety of cyaa forms cation-selective pores and permeabilizes target cell membrane for efflux of cytosolic potassium ions. the non-enzymatic cyaa-ac(-) toxoid, has repeatedly been successf ...201626437769
restricted antibody response to bordetella pertussis filamentous hemagglutinin induced by whole-cell and acellular pertussis vaccines.filamentous hemagglutinin (fha) is a principal virulence factor, an important immunogenic antigen of bordetella pertussis, and a major component of many acellular pertussis vaccines. in the present study, the human antibody response to different regions of fha was determined in healthy children and adults vaccinated with either whole-cell or acellular pertussis vaccines.201626439274
rapid detection of acinetobacter baumannii and molecular epidemiology of carbapenem-resistant a. baumannii in two comprehensive hospitals of beijing, china.acinetobacter baumannii is an important opportunistic pathogen associated with a variety of nosocomial infections. a rapid and sensitive molecular detection in clinical isolates is quite needed for the appropriate therapy and outbreak control of a. baumannii. group 2 carbapenems have been considered the agents of choice for the treatment of multiple drug-resistant a. baumannii. but the prevalence of carbapenem-resistant a. baumannii (crab) has been steadily increasing in recent years. here, we d ...201526441924
pathologic and protective roles for microglial subsets and bone marrow- and blood-derived myeloid cells in central nervous system inflammation.inflammation is a series of processes designed for eventual clearance of pathogens and repair of damaged tissue. in the context of autoimmune recognition, inflammatory processes are usually considered to be pathological. this is also true for inflammatory responses in the central nervous system (cns). however, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes. the complex role of encephalitogenic t cells in multiple sclerosis and its animal model experim ...201526441968
the dna exonucleases of escherichia coli.dna exonucleases, enzymes that hydrolyze phosphodiester bonds in dna from a free end, play important cellular roles in dna repair, genetic recombination and mutation avoidance in all organisms. this article reviews the structure, biochemistry, and biological functions of the 17 exonucleases currently identified in the bacterium escherichia coli. these include the exonucleases associated with dna polymerases i (pola), ii (polb), and iii (dnaq/mutd); exonucleases i (xona/sbcb), iii (xtha), iv, vii ...201126442508
assembly of outer membrane β-barrel proteins: the bam complex.the major class of integral proteins found in the outer membrane (om) of e. coli and salmonella adopt a β-barrel conformation (omps). omps are synthesized in the cytoplasm with a typical signal sequence at the amino terminus, which directs them to the secretion machinery (secyeg) located in the inner membrane for translocation to the periplasm. chaperones such as sura, or degp and skp, escort these proteins across the aqueous periplasm protecting them from aggregation. the chaperones then delive ...201126442509
type v secretion: the autotransporter and two-partner secretion pathways.the autotransporter and two-partner secretion (tps) pathways are used by e. coli and many other gram-negative bacteria to delivervirulence factors into the extracellular milieu.autotransporters arecomprised of an n-terminal extracellular ("passenger") domain and a c-terminal β barrel domain ("β domain") that anchors the protein to the outer membrane and facilitates passenger domain secretion. in the tps pathway, a secreted polypeptide ("exoprotein") is coordinately expressed with an outer membra ...201026443787
[antigenic variability of bordetella pertussis strains isolated in 1967-2010 in the czech republic--possible explanation for the rise in cases of pertussis?].comparison of antigenic structures of bordetella pertussis (b. pertussis) strains isolated from 1967 to 2010 in the czech republic.201526448300
aging diminishes the resistance of ao rats to eae: putative role of enhanced generation of gm-csf expressing cd4+ t cells in aged rats.aging influences immune response and susceptibility to eae in a strain specific manner. the study was designed to examine influence of aging on eae induction in albino oxford (ao) rats.201526448779
edwardsiella tarda esce (orf13 protein) is a type iii secretion system-secreted protein that is required for the injection of effectors, secretion of translocators, and pathogenesis in fish.the type iii secretion system (t3ss) of edwardsiella tarda is crucial for its intracellular survival and pathogenesis in fish. the orf13 gene (esce) of e. tarda is located 84 nucleotides (nt) upstream of esrc in the t3ss gene cluster. we found that esce is secreted and translocated in a t3ss-dependent manner and that amino acids 2 to 15 in the n terminus were required for a completely functional t3ss in e. tarda. deletion of esce abolished the secretion of t3ss translocators, as well as the secr ...201526459509
edwardsiella tarda esce (orf13 protein) is a type iii secretion system-secreted protein that is required for the injection of effectors, secretion of translocators, and pathogenesis in fish.the type iii secretion system (t3ss) of edwardsiella tarda is crucial for its intracellular survival and pathogenesis in fish. the orf13 gene (esce) of e. tarda is located 84 nucleotides (nt) upstream of esrc in the t3ss gene cluster. we found that esce is secreted and translocated in a t3ss-dependent manner and that amino acids 2 to 15 in the n terminus were required for a completely functional t3ss in e. tarda. deletion of esce abolished the secretion of t3ss translocators, as well as the secr ...201526459509
diversity of secretion systems associated with virulence characteristics of the classical bordetellae.secretion systems are key virulence factors, modulating interactions between pathogens and the host's immune response. six potential secretion systems (types 1-6; t1ss-t6ss) have been discussed in classical bordetellae, respiratory commensals/pathogens of mammals. the prototypical bordetella bronchiseptica strain rb50 genome seems to contain all six systems, whilst two human-restricted subspecies, bordetella parapertussis and bordetella pertussis, have lost different subsets of these. this impli ...201526459829
plasmacytoid dendritic cell-derived ifnα modulates th17 differentiation during early bordetella pertussis infection in mice.whooping cough is a highly contagious respiratory disease caused by bordetella pertussis (b. pertussis). t helper 17 (th17) cells have a central role in the resolution of the infection. emerging studies document that type i interferons (ifns) suppress th17 differentiation and interleukin (il)-17 responses in models of infection and chronic inflammation. as plasmacytoid dendritic cells (pdcs) are a major source of type i ifns, we hypothesize that during b. pertussis infection in mice, pdc-derived ...201626462419
structural and functional features of a developmentally regulated lipopolysaccharide-binding protein.mammalian lipopolysaccharide (lps) binding proteins (lbps) occur mainly in extracellular fluids and promote lps delivery to specific host cell receptors. the function of lbps has been studied principally in the context of host defense; the possible role of lbps in nonpathogenic host-microbe interactions has not been well characterized. using the euprymna scolopes-vibrio fischeri model, we analyzed the structure and function of an lbp family protein, e. scolopes lbp1 (eslbp1), and provide evidenc ...201526463160
interdicting gq activation in airway disease by receptor-dependent and receptor-independent mechanisms.gαqβγ heterotrimer (gq), an important mediator in the pathology of airway disease, plays a central role in bronchoconstriction and airway remodeling, including airway smooth muscle growth and inflammation. current therapeutic strategies to treat airway disease include the use of muscarinic and leukotriene receptor antagonists; however, these pharmaceuticals demonstrate a limited clinical efficacy as multiple gq-coupled receptor subtypes contribute to these pathologies. thus, broadly inhibiting t ...201626464325
under-recognized pertussis in adults from asian countries: a cross-sectional seroprevalence study in malaysia, taiwan and thailand.surveillance data on the burden of pertussis in asian adults are limited. this cross-sectional study evaluated the prevalence of serologically confirmed pertussis in adults with prolonged cough in malaysia, taiwan and thailand. adults (⩾19 years) with cough lasting for ⩾14 days without other known underlying cause were enrolled from outpatient clinics of seven public and/or private hospitals. single blood samples for anti-pertussis toxin antibodies (anti-pt igg) were analysed and economic impact ...201526468043
under-recognized pertussis in adults from asian countries: a cross-sectional seroprevalence study in malaysia, taiwan and thailand.surveillance data on the burden of pertussis in asian adults are limited. this cross-sectional study evaluated the prevalence of serologically confirmed pertussis in adults with prolonged cough in malaysia, taiwan and thailand. adults (⩾19 years) with cough lasting for ⩾14 days without other known underlying cause were enrolled from outpatient clinics of seven public and/or private hospitals. single blood samples for anti-pertussis toxin antibodies (anti-pt igg) were analysed and economic impact ...201526468043
natural killer cells and innate interferon gamma participate in the host defense against respiratory vaccinia virus infection.in establishing a respiratory infection, vaccinia virus (vacv) initially replicates in airway epithelial cells before spreading to secondary sites of infection, mainly the draining lymph nodes, spleen, gastrointestinal tract, and reproductive organs. we recently reported that interferon gamma (ifn-γ) produced by cd8 t cells ultimately controls this disseminated infection, but the relative contribution of ifn-γ early in infection is unknown. investigating the role of innate immune cells, we found ...201526468539
natural killer cells and innate interferon gamma participate in the host defense against respiratory vaccinia virus infection.in establishing a respiratory infection, vaccinia virus (vacv) initially replicates in airway epithelial cells before spreading to secondary sites of infection, mainly the draining lymph nodes, spleen, gastrointestinal tract, and reproductive organs. we recently reported that interferon gamma (ifn-γ) produced by cd8 t cells ultimately controls this disseminated infection, but the relative contribution of ifn-γ early in infection is unknown. investigating the role of innate immune cells, we found ...201526468539
diagnostic accuracy of c-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic ct scan.community-acquired pneumonia (cap) requires prompt treatment, but its diagnosis is complex. improvement of bacterial cap diagnosis by biomarkers has been evaluated using chest x-ray infiltrate as the cap gold standard, producing conflicting results. we analyzed the diagnostic accuracy of biomarkers in suspected cap adults visiting emergency departments for whom cap diagnosis was established by an adjudication committee which founded its judgment on a systematic multidetector thoracic ct scan.201526472401
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