Publications

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 ...	2015	26371178
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 ...	2015	26389958
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.	2015	26358588
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 ...	2015	26350294
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 ...	2015	26346097
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 ...	2015	26441968
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 ...	2015	26344196
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 ...	2015	26347576
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 ...	2015	26347576
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 ...	2015	26337864
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 ...	2015	26337864
a complex signaling cascade governs pristinamycin biosynthesis in streptomyces pristinaespiralis.	pristinamycin production in streptomyces pristinaespiralis pr11 is tightly regulated by an interplay between different repressors and activators. a γ-butyrolactone receptor gene (spbr), two tetr repressor genes (papr3 and papr5), three sarp (streptomyces antibiotic regulatory protein) genes (papr1, papr2, and papr4), and a response regulator gene (papr6) are carried on the large 210-kb pristinamycin biosynthetic gene region of streptomyces pristinaespiralis pr11. a detailed investigation of all ...	2015	26187956
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 ...	2015	26421291
tracking pertussis and evaluating control measures through enhanced pertussis surveillance, emerging infections program, united states.	despite high coverage with pertussis-containing vaccines, pertussis remains endemic to the united states. there have been increases in reported cases in recent years, punctuated by striking epidemics and shifting epidemiology, both of which raise questions about current policies regarding its prevention and control. limited data on pertussis reported through the national notifiable disease surveillance system have proved insufficient to answer these questions. to address shortcomings of national ...	2015	26291475
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 ...	2015	26327720
mycobacterium tuberculosis oric sequestration by mtra response regulator.	the regulators of mycobacterium tuberculosis dna replication are largely unknown. here, we demonstrate that in synchronously replicating m. tuberculosis, mtra access to origin of replication (oric) is enriched in the post-replication (d) period. the increased oric binding results from elevated mtra phosphorylation (mtra∼p) as evidenced by reduced expression of dnan, dnaa and increased expression of select cell division targets. overproduction of gain-of-function mtray102c advanced the mtra oric ...	2015	26207528
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 ...	2015	26324705
dynamics and energy contributions for transport of unfolded pertactin through a protein nanopore.	to evaluate the physical parameters governing translocation of an unfolded protein across a lipid bilayer, we studied protein transport through aerolysin, a passive protein channel, at the single-molecule level. the protein model used was the passenger domain of pertactin, an autotransporter virulence protein. transport of pertactin through the aerolysin nanopore was detected as transient partial current blockades as the unfolded protein partially occluded the aerolysin channel. we compared the ...	2015	26302243
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 ...	2015	26304458
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 ...	2015	26379661
vaccination of healthcare workers: a review.	vaccine-preventable diseases are a significant cause of morbidity and mortality. as new vaccines are proving to be effective and as the incidence of some infections decreases, vaccination practices are changing. healthcare workers (hcws) are particularly exposed to and play a role in nosocomial transmission, which makes them an important target group for vaccination. most vaccine-preventable diseases still carry a significant risk of resurgence and have caused outbreaks in recent years. while ma ...	2015	26291642
immunization of preterm infants.	vaccinations of premature infants are often delayed despite being at an increased risk of contracting vaccine preventable diseases. this article reviews the current knowledge on the immune response to widely used vaccines, on the protection derived from routine immunization and on vaccine safety and tolerability in a population of preterm infants. available data evaluating the immune response of preterm infants support early immunization without correction for gestational age. for a number of an ...	2015	26291883
rapid fine conformational epitope mapping using comprehensive mutagenesis and deep sequencing.	knowledge of the fine location of neutralizing and non-neutralizing epitopes on human pathogens affords a better understanding of the structural basis of antibody efficacy, which will expedite rational design of vaccines, prophylactics, and therapeutics. however, full utilization of the wealth of information from single cell techniques and antibody repertoire sequencing awaits the development of a high throughput, inexpensive method to map the conformational epitopes for antibody-antigen interac ...	2015	26296891
within-host dynamics of infection: from ecological insights to evolutionary predictions.		2015	26150670
whole-genome sequencing reveals the effect of vaccination on the evolution of bordetella pertussis.	herd immunity can potentially induce a change of circulating viruses. however, it remains largely unknown that how bacterial pathogens adapt to vaccination. in this study, bordetella pertussis, the causative agent of whooping cough, was selected as an example to explore possible effect of vaccination on the bacterial pathogen. we sequenced and analysed the complete genomes of 40 b. pertussis strains from finland and china, as well as 11 previously sequenced strains from the netherlands, where di ...	2015	26283022
examining the role of different age groups, and of vaccination during the 2012 minnesota pertussis outbreak.	there is limited information on the roles of different age groups during pertussis outbreaks. little is known about vaccine effectiveness against pertussis infection (both clinically apparent and subclinical), which is different from effectiveness against reportable pertussis disease, with the former influencing the impact of vaccination on pertussis transmission in the community. for the 2012 pertussis outbreak in minnesota, we estimated odds ratios for case counts in pairs of population groups ...	2015	26278132
a distinct region in erythropoietin that induces immuno/inflammatory modulation and tissue protection.	beneficial effects of short-term whole-molecule erythropoietin (epo) therapy have been demonstrated on several animal models of diverse central nervous system pathology. however, the increased hematocrit induced by epo-driven marrow stimulation greatly limits its potential for side effect-free therapy. we created a library of epo-derived fragments based on the hypothesis that 2 distinct functions, erythropoiesis and tissue protection, reside in different regions of the molecule. several small ep ...	2015	26271954
can near-infrared spectroscopy detect and differentiate implant-associated biofilms?	established bacterial diagnostic techniques for orthopaedic-related infections rely on a combination of imperfect tests that often can lead to negative culture results. spectroscopy is a tool that potentially could aid in rapid detection and differentiation of bacteria in implant-associated infections.	2015	26265208
a novel pathogenic rbp-3 peptide reveals epitope spreading in persistent experimental autoimmune uveoretinitis.	experimental autoimmune uveoretinitis (eau) in the c57bl/6j mouse is a model of non-infectious posterior segment intraocular inflammation that parallels clinical features of the human disease. the purpose of this study was to analyse the immune response to the four murine subunits of retinol binding protein-3 (rbp-3) to identify pathogenic epitopes to investigate the presence of intramolecular epitope spreading during the persistent inflammation phase observed in this model of eau. recombinant m ...	2015	26152845
cross talk inhibition nullified by a receiver domain missense substitution.	in two-component signal transduction, a sensor protein transmitter module controls cognate receiver domain phosphorylation. most receiver domain sequences contain a small residue (gly or ala) at position t + 1 just distal to the essential thr or ser residue that forms part of the active site. however, some members of the narl receiver subfamily have a large hydrophobic residue at position t + 1. our laboratory previously isolated a narl mutant in which the t + 1 residue val-88 was replaced with ...	2015	26260457
what to do about pertussis vaccines? linking what we know about pertussis vaccine effectiveness, immunology and disease transmission to create a better vaccine.	pertussis (whooping cough) is a respiratory disease caused by the bacterium bordetella pertussis. despite the implementation of immunization programs and high vaccine coverage in most jurisdictions, pertussis is still one of the most common vaccine-preventable diseases, suggesting that the current vaccines and immunization schedules have not been sufficiently effective. several factors are thought to contribute to this. the acellular pertussis vaccine that has been used in many jurisdictions sin ...	2015	26253079
a broadly cross-protective vaccine presenting the neighboring epitopes within the vp1 gh loop and vp2 ef loop of enterovirus 71.	human enterovirus 71 (ev71) and coxsackievirus a16 (ca16) are the major etiological agents of hand, foot and mouth disease (hfmd) and are often associated with neurological complications. currently, several vaccine types are being developed for ev71 and ca16. in this study, we constructed a bivalent chimeric virus-like particle (vlp) presenting the vp1 (aa208-222) and vp2 (aa141-155) epitopes of ev71 using hepatitis b virus core protein (hbc) as a carrier, designated hbc-e1/2. immunization with ...	2015	26243660
an essential poison: synthesis and degradation of cyclic di-amp in bacillus subtilis.	gram-positive bacteria synthesize the second messenger cyclic di-amp (c-di-amp) to control cell wall and potassium homeostasis and to secure the integrity of their dna. in the firmicutes, c-di-amp is essential for growth. the model organism bacillus subtilis encodes three diadenylate cyclases and two potential phosphodiesterases to produce and degrade c-di-amp, respectively. among the three cyclases, cdaa is conserved in nearly all firmicutes, and this enzyme seems to be responsible for the c-di ...	2015	26240071
occupational exposure to dromedaries and risk for mers-cov infection, qatar, 2013-2014.	we determined the presence of neutralizing antibodies to middle east respiratory syndrome coronavirus in persons in qatar with and without dromedary contact. antibodies were only detected in those with contact, suggesting dromedary exposure as a risk factor for infection. findings also showed evidence for substantial underestimation of the infection in populations at risk in qatar.	2015	26196891
outbreak of mycoplasma pneumoniae-associated stevens-johnson syndrome.	stevens-johnson syndrome (sjs) is an uncommon, sporadic disease and outbreaks are rare. in november 2013, an outbreak of sjs was identified at children's hospital colorado.	2015	26216320
new approaches to understanding the immune response to vaccination and infection.	the immune system is a network of specialized cell types and tissues that communicates via cytokines and direct contact, to orchestrate specific types of defensive responses. until recently, we could only study immune responses in a piecemeal, highly focused fashion, on major components like antibodies to the pathogen. but recent advances in technology and in our understanding of the many components of the system, innate and adaptive, have made possible a broader approach, where both the multipl ...	2015	26232539
t(h)17-mediated protection against pneumococcal carriage by a whole-cell vaccine is dependent on toll-like receptor 2 and surface lipoproteins.	a pneumococcal whole-cell vaccine (wcv) confers t(h)17-mediated immunogenicity and reduces nasopharyngeal (np) carriage in mice. activation of toll-like receptor 2 (tlr2) has been shown to be important for generating t(h)17 responses, and several lipidated pneumococcal proteins have tlr2-activating properties. here we investigated the roles of tlr2 and lipidation of proteins in wcv-induced interleukin-17a (il-17a) responses and protection against np carriage. immunization of tlr2(-/-) mice with ...	2015	26041040
acylation enhances, but is not required for, the cytotoxic activity of mannheimia haemolytica leukotoxin in bighorn sheep.	mannheimia haemolytica causes pneumonia in domestic and wild ruminants. leukotoxin (lkt) is the most important virulence factor of the bacterium. it is encoded within the four-gene lktcabd operon: lkta encodes the structural protoxin, and lktc encodes a trans-acylase that adds fatty acid chains to internal lysine residues in the protoxin, which is then secreted from the cell by a type 1 secretion system apparatus encoded by lktb and lktd. it has been reported that lktc-mediated acylation is nece ...	2015	26216418
covrs-regulated transcriptome analysis of a hypervirulent m23 strain of group a streptococcus pyogenes provides new insights into virulence determinants.	the two-component control of virulence (cov) regulator (r)-sensor (s) (covrs) regulates the virulence of streptococcus pyogenes (group a streptococcus [gas]). inactivation of covs during infection switches the pathogenicity of gas to a more invasive form by regulating transcription of diverse virulence genes via covr. however, the manner in which covrs controls virulence through expression of extended gene families has not been fully determined. in the current study, the covs-regulated gene expr ...	2015	26216843
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.	2015	26396713
cell fusion along the anterior-posterior neuroaxis in mice with experimental autoimmune encephalomyelitis.	it is well documented that bone marrow-derived cells can fuse with a diverse range of cells, including brain cells, under normal or pathological conditions. inflammation leads to robust fusion of bone marrow-derived cells with purkinje cells and the formation of binucleate heterokaryons in the cerebellum. heterokaryons form through the fusion of two developmentally differential cells and as a result contain two distinct nuclei without subsequent nuclear or chromosome loss.	2015	26207625
s100b up-regulates macrophage production of il1β and ccl22 and influences severity of retinal inflammation.	s100b is a ca2+ binding protein and is typically associated with brain and cns disorders. however, the role of s100b in an inflammatory situation is not clear. the aim of the study was to determine whether s100b is likely to influence inflammation through its effect on macrophages. a murine macrophage cell line (raw 264.7) and primary bone marrow derived macrophages were used for in vitro studies and a model of retinal inflammatory disease in which pathogenesis is highly dependent on macrophage ...	2015	26204512
the tatc component of the twin-arginine protein translocase functions as an obligate oligomer.	the tat protein export system translocates folded proteins across the bacterial cytoplasmic membrane and the plant thylakoid membrane. the tat system in escherichia coli is composed of tata, tatb and tatc proteins. tatb and tatc form an oligomeric, multivalent receptor complex that binds tat substrates, while multiple protomers of tata assemble at substrate-bound tatbc receptors to facilitate substrate transport. we have addressed whether oligomerisation of tatc is an absolute requirement for op ...	2015	26112072
signal transduction by bvgs sensor kinase: binding of modulator nicotinate affects the conformation and dynamics of the entire periplasmic moiety.	the two-component sensory transduction system bvgas controls the virulence regulon of the whooping-cough agent bordetella pertussis. the periplasmic moiety of the homodimeric sensor kinase bvgs is composed of four bilobed venus flytrap (vft) perception domains followed by α helices that extend into the cytoplasmic membrane. in the virulent phase, the default state of b. pertussis, the cytoplasmic enzymatic moiety of bvgs acts as kinase by autophosphorylating and transferring the phosphoryl group ...	2015	26203186
erratum for boinett et al., complete genome sequence of bordetella pertussis d420.		2015	26184951
the resurgence of pertussis.		2015	25852038
different roles of n-terminal and c-terminal domains in calmodulin for activation of bacillus anthracis edema factor.	bacillus anthracis adenylyl cyclase toxin edema factor (ef) is one component of the anthrax toxin and is essential for establishing anthrax disease. ef activation by the eukaryotic ca2+-sensor calmodulin (cam) leads to massive camp production resulting in edema. camp also inhibits the nicotinamide adenine dinucleotide phosphate (nadph)-oxidase, thus reducing production of reactive oxygen species (ros) used for host defense in activated neutrophils and thereby facilitating bacterial growth. methi ...	2015	26184312
mir-181a-1/b-1 modulates tolerance through opposing activities in selection and peripheral t cell function.	understanding the consequences of tuning tcr signaling on selection, peripheral t cell function, and tolerance in the context of native tcr repertoires may provide insight into the physiological control of tolerance. in this study, we show that genetic ablation of a natural tuner of tcr signaling, mir-181a-1/b-1, in double-positive thymocytes dampened tcr and erk signaling and increased the threshold of positive selection. whereas mir-181a-1/b-1 deletion in mice resulted in an increase in the in ...	2015	26163591
dual function of the irf8 transcription factor in autoimmune uveitis: loss of irf8 in t cells exacerbates uveitis, whereas irf8 deletion in the retina confers protection.	ifn regulatory factor 8 (irf8) is constitutively expressed in monocytes and b cells and plays a critical role in the functional maturation of microglia cells. it is induced in t cells following ag stimulation, but its functions are less well understood. however, recent studies in mice with t cell-specific irf8 disruption under direction of the lck promoter (lck-irf8ko) suggest that irf8 directs a silencing program for th17 differentiation, and il-17 production is markedly increased in irf8-defic ...	2015	26163590
current advances and challenges in the development of acinetobacter vaccines.	acinetobacter baumannii is a major cause of healthcare-associated infections worldwide with high morbidity and mortality. the clinical treatment of a. baumannii infections has become increasingly difficult because of the rapid emerging of multidrug and extremely drug resistant strains. thus, there is an urgent need for the development of novel intervention strategies to combat this multidrug-resistant pathogen. vaccine is one of the most effective medical measures for infection control and is li ...	2015	26158773
activation of human toll-like receptor 4 (tlr4)·myeloid differentiation factor 2 (md-2) by hypoacylated lipopolysaccharide from a clinical isolate of burkholderia cenocepacia.	lung infection by burkholderia species, in particular burkholderia cenocepacia, accelerates tissue damage and increases post-lung transplant mortality in cystic fibrosis patients. host-microbe interplay largely depends on interactions between pathogen-specific molecules and innate immune receptors such as toll-like receptor 4 (tlr4), which recognizes the lipid a moiety of the bacterial lipopolysaccharide (lps). the human tlr4·myeloid differentiation factor 2 (md-2) lps receptor complex is strong ...	2015	26160169
functional characterization of the receiver domain for phosphorelay control in hybrid sensor kinases.	hybrid sensor kinase, which contains a histidine kinase (hk) domain, a receiver domain, and a histidine-containing phosphotransmitter (hpt) domain, conveys signals to its cognate response regulator by means of a his-asp-his-asp phosphorelay. we examined the multistep phosphorelay of a recombinant evgas system in escherichia coli and performed in vitro quantitative analyses of phosphorylation by using phos-tag sds-page. replacement of asp in the receiver domain of evgs by ala markedly promoted ph ...	2015	26151934
antigenic stimulation of kv1.3-deficient th cells gives rise to a population of foxp3-independent t cells with suppressive properties.	multiple sclerosis (ms) is an immune-mediated demyelinating disease of the cns that has been linked with defects in regulatory t cell function. therefore, strategies to selectively target pathogenic cells via enhanced regulatory t cell activity may provide therapeutic benefit. kv1.3 is a voltage-gated potassium channel expressed on myelin-reactive t cells from ms patients. kv1.3-knockout (ko) mice are protected from experimental autoimmune encephalomyelitis, an animal model of ms, and kv1.3-ko t ...	2015	26150529
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 ...	2015	26396975
evasion and interactions of the humoral innate immune response in pathogen invasion, autoimmune disease, and cancer.	the humoral innate immune system is composed of three major branches, complement, coagulation, and natural antibodies. to persist in the host, pathogens, such as bacteria, viruses, and cancers must evade parts of the innate humoral immune system. disruptions in the humoral innate immune system also play a role in the development of autoimmune diseases. this review will examine how gram positive bacteria, viruses, cancer, and the autoimmune conditions systemic lupus erythematosus and anti-phospho ...	2015	26145788
sensor-response regulator interactions in a cross-regulated signal transduction network.	two-component signal transduction involves phosphoryl transfer between a histidine kinase sensor and a response regulator effector. the nitrate-responsive two-component signal transduction systems in escherichia coli represent a paradigm for a cross-regulation network, in which the paralogous sensor-response regulator pairs, narx-narl and narq-narp, exhibit both cognate (e.g. narx-narl) and non-cognate (e.g. narq-narl) interactions to control output. here, we describe results from bacterial aden ...	2015	25873583
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 ...	2015	26413316
serum reactome induced by bordetella pertussis infection and pertussis vaccines: qualitative differences in serum antibody recognition patterns revealed by peptide microarray analysis.	pertussis (whooping cough) remains a public health problem despite extensive vaccination strategies. better understanding of the host-pathogen interaction and the detailed b. pertussis (bp) target recognition pattern will help in guided vaccine design. we characterized the specific epitope antigen recognition profiles of serum antibodies ('the reactome') induced by whooping cough and b. pertussis (bp) vaccines from a case-control study conducted in 1996 in infants enrolled in a bp vaccine trial ...	2015	26129684
single nucleotide polymorphisms in the bovine histophilus somni genome; a comparison of new and old isolates.	histophilus somni, a causative agent of the bovine respiratory disease complex, can also cause a variety of systemic disorders, including bronchopneumonia, myocarditis, pericarditis, arthritis, pleuritis, and infectious thrombotic meningoencephalitis. the purpose of this study was to determine if currently circulating strains differ from those of the 1980s by identifying genomic changes. single nucleotide polymorphisms (snps) and insertion and deletion (indel) sites were examined by whole-genome ...	2015	26130851
pertussis: the resurgence of a public health threat.	pertussis is an acute and very contagious pulmonary disease, clinically characterized by periods of coughing and paroxysms that may cause death. the disease afflicts mainly the pediatric population and is life threatening to children under the age of 1 year. since the beginning of the second millennium, the number of cases of pertussis has increased, menacing public health, despite the availability of the pertussis vaccine. the resurgence of the disease among adults and older children creates a ...	2015	26484329
pertussis in young infants: a severe vaccine-preventable disease.		2015	26484327
treatment of chronic experimental autoimmune encephalomyelitis with epigallocatechin-3-gallate and glatiramer acetate alters expression of heme-oxygenase-1.	we previously demonstrated that epigallocatechin-3-gallate (egcg) synergizes with the immunomodulatory agent glatiramer acetate (ga) in eliciting anti-inflammatory and neuroprotective effects in the relapsing-remitting eae model. thus, we hypothesized that mice with chronic eae may also benefit from this combination therapy. we first assessed how a treatment with a single dose of ga together with daily application of egcg may modulate eae. although single therapies with a suboptimal dose of ga o ...	2015	26114502
asymptomatic transmission and the resurgence of bordetella pertussis.	the recent increase in whooping cough incidence (primarily caused by bordetella pertussis) presents a challenge to both public health practitioners and scientists trying to understand the mechanisms behind its resurgence. three main hypotheses have been proposed to explain the resurgence: 1) waning of protective immunity from vaccination or natural infection over time, 2) evolution of b. pertussis to escape protective immunity, and 3) low vaccine coverage. recent studies have suggested a fourth ...	2015	26103968
universal tetanus, diphtheria, acellular pertussis (tdap) vaccination of adults: what canadian health care providers know and need to know.	the tetanus, diphtheria, and acellular pertussis vaccine (tdap) is recommended for all adults in both canada and the united states. there are few data on the proportion of canadian adults vaccinated with tdap; however, anecdotal reports indicate that uptake is low. this study aimed to explore the knowledge, attitudes, beliefs, and behaviors of canadian health care providers (hcps) in an attempt to identify potential barriers and facilitators to tdap uptake. hcps were surveyed and a geographic an ...	2015	26090861
topical administration of a suppressor of cytokine signaling-1 (socs1) mimetic peptide inhibits ocular inflammation and mitigates ocular pathology during mouse uveitis.	uveitis is a diverse group of potentially sight-threatening intraocular inflammatory diseases and pathology derives from sustained production of pro-inflammatory cytokines in the optical axis. although topical or systemic steroids are effective therapies, their adverse effects preclude prolonged usage and are impetus for seeking alternative immunosuppressive agents, particularly for patients with refractory uveitis. in this study, we synthesized a 16 amino acid membrane-penetrating lipophilic su ...	2015	26094775
can immunological principles and cross-disciplinary science illuminate the path to vaccines for hiv and other global health challenges?	vaccines are one of the most impactful and cost-effective public health measures of the twentieth century. however, there remain great unmet needs to develop vaccines for globally burdensome infectious diseases and to allow more timely responses to emerging infectious disease threats. recent advances in the understanding of immunological principles operative not just in model systems but in humans in concert with the development and application of powerful new tools for profiling human immune re ...	2015	25964461
respiratory infections in the u.s. military: recent experience and control.	this comprehensive review outlines the impact of military-relevant respiratory infections, with special attention to recruit training environments, influenza pandemics in 1918 to 1919 and 2009 to 2010, and peacetime operations and conflicts in the past 25 years. outbreaks and epidemiologic investigations of viral and bacterial infections among high-risk groups are presented, including (i) experience by recruits at training centers, (ii) impact on advanced trainees in special settings, (iii) morb ...	2015	26085551
inhibition of system xc(-) transporter attenuates autoimmune inflammatory demyelination.	t cell infiltration into the cns is a significant underlying pathogenesis in autoimmune inflammatory demyelinating diseases. several lines of evidence suggest that glutamate dysregulation in the cns is an important consequence of immune cell infiltration in neuroinflammatory demyelinating diseases; yet, the causal link between inflammation and glutamate dysregulation is not well understood. a major source of glutamate release during oxidative stress is the system xc(-) transporter; however, this ...	2015	26071560
complete genome sequence of bordetella pertussis d420.	bordetella pertussis is the causative agent of whooping cough, a highly contagious, acute respiratory illness that has seen resurgence despite the use of vaccines. we present the complete genome sequence of a clinical strain of b. pertussis, d420, which is representative of a currently circulating clade of this pathogen.	2015	26067980
bacterial determinants of importance in the virulence of gallibacterium anatis in poultry.	gallibacterium anatis, a member of the pasteurellaceae family, constitute a part of the normal micro-flora of the upper respiratory tract and the lower genital tract in chickens. however, increasing evidence indicate that g. anatis is also associated with a wide range of pathological changes, particularly in the reproductive organs, which leads to decreased egg production, lowered animal welfare and increased mortality. as a recently defined opportunistic pathogen limited focus has been placed o ...	2015	26063044
conserved omp85 lid-lock structure and substrate recognition in fhac.	omp85 proteins mediate translocation of polypeptide substrates across and into cellular membranes. they share a common architecture comprising substrate-interacting potra domains, a c-terminal 16-stranded β-barrel pore and two signature motifs located on the inner barrel wall and at the tip of the extended l6 loop. the observation of two distinct conformations of the l6 loop in the available omp85 structures previously suggested a functional role of conformational changes in l6 in the omp85 mech ...	2015	26058369
pertussis prevalence in korean adolescents and adults with persistent cough.	we investigated the prevalence of pertussis in korean adolescents and adults with persistent cough. study population was adolescents (aged 11-20 yr) and adults (≥ 21 yr old) who showed persistent cough of 1-8 weeks' duration. pertussis was diagnosed by culture, polymerase chain reaction (pcr), and serology. a total of 310 subjects participated in this study, and 76 cases (24.5%) met the criteria for laboratory-confirmed pertussis. the majority of the pertussis cases (66/76) were confirmed by ser ...	2015	26130965
the role of g-protein receptor 84 in experimental neuropathic pain.	g-protein receptor 84 (gpr84) is an orphan receptor that is induced markedly in monocytes/macrophages and microglia during inflammation, but its pathophysiological function is unknown. here, we investigate the role of gpr84 in a murine model of traumatic nerve injury. naive gpr84 knock-out (ko) mice exhibited normal behavioral responses to acute noxious stimuli, but subsequent to partial sciatic nerve ligation (pnl), kos did not develop mechanical or thermal hypersensitivity, in contrast to wild ...	2015	26063927
knowledge and acceptability about adult pertussis immunization in korean women of childbearing age.	the adult tetanus, reduced diphtheria, and acellular pertussis (tdap) vaccine has been introduced in order to provide individual protection and reduce the risk of transmitting pertussis to infants. we assessed the knowledge and acceptability of the tdap vaccine around pregnancy.	2015	26069132
inhibition of nos-no system prevents autoimmune orchitis development in rats: relevance of no released by testicular macrophages in germ cell apoptosis and testosterone secretion.	although the testis is considered an immunoprivileged organ it can orchestrate immune responses against pathological insults such as infection and trauma. experimental autoimmune orchitis (eao) is a model of chronic inflammation whose main histopathological features it shares with human orchitis. in eao an increased number of macrophages infiltrate the interstitium concomitantly with progressive germ cell degeneration and impaired steroidogenesis. up-regulation of nitric oxide (no)-no synthase ( ...	2015	26046347
transfer of myelin-reactive th17 cells impairs endogenous remyelination in the central nervous system of cuprizone-fed mice.	multiple sclerosis (ms) is a demyelinating disease of the cns characterized by inflammation and neurodegeneration. animal models that enable the study of remyelination in the context of ongoing inflammation are greatly needed for the development of novel therapies that target the pathological inhibitory cues inherent to the ms plaque microenvironment. we report the development of an innovative animal model combining cuprizone-mediated demyelination with transfer of myelin-reactive cd4(+) t cells ...	2015	26041928
estimated human and economic burden of four major adult vaccine-preventable diseases in the united states, 2013.	low uptake of routinely recommended adult immunizations is a public health concern. using data from the peer-reviewed literature, government disease-surveillance programs, and the us census, we developed a customizable model to estimate human and economic burden caused by four major adult vaccine-preventable diseases (vpd) in 2013 in the united states, and for each us state individually. to estimate the number of cases for each adult vpd for a given population, we multiplied age-specific inciden ...	2015	26032932
multifunctional-autoprocessing repeats-in-toxin (martx) toxins of vibrios.	multifunctional-autoprocessing repeats-in-toxin (martx) toxins are a heterogeneous group of toxins found in a number of vibrio species and other gram-negative bacteria. the toxins are composed of conserved repeat regions and an autoprocessing protease domain that together function as a delivery platform for transfer of cytotoxic and cytopathic domains into target eukaryotic cell cytosol. within the cells, the effectors can alter biological processes such as signaling or cytoskeletal structure, p ...	2015	26185092
suppression of peripheral pain by blockade of voltage-gated calcium 2.2 channels in nociceptors induces rankl and impairs recovery from inflammatory arthritis in a mouse model.	a hallmark of rheumatoid arthritis (ra) is the chronic pain that accompanies inflammation and joint deformation. patients with ra rate pain relief as the highest priority; however, few studies have addressed the efficacy and safety of therapies directed specifically toward pain pathways. the ω-conotoxin mviia (ziconotide) is used in humans to alleviate persistent pain syndromes, because it specifically blocks the voltage-gated calcium 2.2 (cav 2.2) channel, which mediates the release of neurotra ...	2015	25733371
bordetella pertussis is an uncommon pathogen in children hospitalized with bronchiolitis during the winter season.	in the united states (u.s.), bordetella pertussis incidence has increased. cough and apnea are common findings in pertussis and also in bronchiolitis, the most common cause of hospitalization in u.s. infants. the objective was to determine the prevalence of b. pertussis infection in children hospitalized with bronchiolitis and to describe its clinical course.	2015	25970109
structure of a bacterial toxin-activating acyltransferase.	secreted pore-forming toxins of pathogenic gram-negative bacteria such as escherichia coli hemolysin (hlya) insert into host-cell membranes to subvert signal transduction and induce apoptosis and cell lysis. unusually, these toxins are synthesized in an inactive form that requires posttranslational activation in the bacterial cytosol. we have previously shown that the activation mechanism is an acylation event directed by a specialized acyl-transferase that uses acyl carrier protein (acp) to cov ...	2015	26016525
dynamics of pertussis transmission in the united states.	past patterns of infectious disease transmission set the stage on which modern epidemiologic dynamics are played out. here, we present a comprehensive account of pertussis (whooping cough) transmission in the united states during the early vaccine era. we analyzed recently digitized weekly incidence records from morbidity and mortality weekly reports from 1938 to 1955, when the whole-cell pertussis vaccine was rolled out, and related them to contemporary patterns of transmission and resurgence d ...	2015	26022662
critical components of the conjugation machinery of the integrative and conjugative element icebs1 of bacillus subtilis.	conjugation, or mating, plays a profound role in bacterial evolution by spreading genes that allow bacteria to adapt to and colonize new niches. icebs1, an integrative and conjugative element of bacillus subtilis, can transfer itself and mobilize resident plasmids. dna transfer is mediated by a type iv secretion system (t4ss). characterized components of the icebs1 t4ss include the conserved virb4-like atpase cone, the bifunctional cell wall hydrolase cwlt, and the presumed vird4-like coupling p ...	2015	26013486
structural, functional, and genetic analyses of the actinobacterial transcription factor rbpa.	gene expression is highly regulated at the step of transcription initiation, and transcription activators play a critical role in this process. rbpa, an actinobacterial transcription activator that is essential in mycobacterium tuberculosis (mtb), binds selectively to group 1 and certain group 2 σ-factors. to delineate the molecular mechanism of rbpa, we show that the mtb rbpa σ-interacting domain (sid) and basic linker are sufficient for transcription activation. we also present the crystal str ...	2015	26040003
harnessing the therapeutic potential of th17 cells.	th17 cells provide protective immunity to infections by fungi and extracellular bacteria as well as cancer but are also involved in chronic inflammation. the cells were first identified by their ability to produce interleukin 17a (il-17a) and, subsequently, associated with chronic inflammation and autoimmunity. th17 cells have some gene profile similarity with stem cells and can remain dormant in mucosal tissues for long periods. indeed, recent studies suggest that functionally distinct subsets ...	2015	26101460
a multiprotein dna translocation complex directs intramycelial plasmid spreading during streptomyces conjugation.	conjugative dna transfer in mycelial streptomyces is a unique process involving the transfer of a double-stranded plasmid from the donor into the recipient and the subsequent spreading of the transferred plasmid within the recipient mycelium. this process is associated with growth retardation of the recipient and manifested by the formation of circular inhibition zones, named pocks. to characterize the unique streptomyces dna transfer machinery, we replaced each gene of the conjugative 12.1-kbp ...	2015	26015502
prime-boost vaccination with toxoplasma lysate antigen, but not with a mixture of recombinant protein antigens, leads to reduction of brain cyst formation in balb/c mice.	infection with the ubiquitous parasite toxoplasma gondii is a threat for immunocompromised patients and pregnant women and effective immune-prophylaxis is still lacking.	2015	26010355
a proteomic characterization of bordetella pertussis clinical isolates associated with a california state pertussis outbreak.	bordetella pertussis (bp) is the etiologic agent of pertussis (whooping cough), a highly communicable infection. although pertussis is vaccine preventable, in recent years there has been increased incidence, despite high vaccine coverage. possible reasons for the rise in cases include the following: bp strain adaptation, waning vaccine immunity, increased surveillance, and improved clinical diagnostics. a pertussis outbreak impacted california (usa) in 2010; children and preadolescents were the ...	2015	26090226
c-di-gmp regulates pseudomonas aeruginosa stress response to tellurite during both planktonic and biofilm modes of growth.	stress response plays an important role on microbial adaptation under hostile environmental conditions. it is generally unclear how the signaling transduction pathway mediates a stress response in planktonic and biofilm modes of microbial communities simultaneously. here, we showed that metalloid tellurite (teo3(2-)) exposure induced the intracellular content of the secondary messenger cyclic di-gmp (c-di-gmp) of pseudomonas aeruginosa. two diguanylate cyclases (dgcs), sadc and siad, were respon ...	2015	25992876
virulence gene regulation by l-arabinose in salmonella enterica.	invasion of the intestinal epithelium is a critical step in salmonella enterica infection and requires functions encoded in the gene cluster known as salmonella pathogenicity island 1 (spi-1). expression of spi-1 genes is repressed by l-arabinose, and not by other pentoses. transport of l-arabinose is necessary to repress spi-1; however, repression is independent of l-arabinose metabolism and of the l-arabinose-responsive regulator arac. spi-1 repression by l-arabinose is exerted at a single tar ...	2015	25991823
immunostimulatory effects triggered by enterococcus faecalis cect7121 probiotic strain involve activation of dendritic cells and interferon-gamma production.	probiotics can modulate the immune system, conferring beneficial effects on the host. understanding how these microorganisms contribute to improve the health status is still a challenge. previously, we have demonstrated that enterococcus faecalis cect7121 implants itself and persists in the murine gastrointestinal tract, and enhances and skews the profile of cytokines towards the th1 phenotype in several biological models. given the importance of dendritic cells (dcs) in the orchestration of imm ...	2015	25978357
treatment with vitamin d/mog association suppresses experimental autoimmune encephalomyelitis.	experimental autoimmune encephalomyelitis (eae) is an animal model to study multiple sclerosis (ms). considering the tolerogenic effects of active vitamin d, we evaluated the therapeutic effect of myelin oligodendrocyte glycoprotein (mog) associated with active vitamin d in eae development. eae was induced in female c57bl/6 mice by immunization with mog emulsified with complete freund's adjuvant plus mycobacterium tuberculosis. animals also received two intraperitoneal doses of bordetella pertus ...	2015	25965341
induction of the nitrate assimilation nira operon and protein-protein interactions in the maturation of nitrate and nitrite reductases in the cyanobacterium anabaena sp. strain pcc 7120.	nitrate is widely used as a nitrogen source by cyanobacteria, in which the nitrate assimilation structural genes frequently constitute the so-called nira operon. this operon contains the genes encoding nitrite reductase (nira), a nitrate/nitrite transporter (frequently an abc-type transporter; nrtabcd), and nitrate reductase (narb). in the model filamentous cyanobacterium anabaena sp. strain pcc 7120, which can fix n2 in specialized cells termed heterocysts, the nira operon is expressed at high ...	2015	25962912
the in-vivo use of superparamagnetic iron oxide nanoparticles to detect inflammation elicits a cytokine response but does not aggravate experimental arthritis.	superparamagnetic iron oxide nanoparticles (spion) are used in diagnostic imaging of a variety of different diseases. for such in-vivo application, an additional coating with a polymer, for example polyvinyl alcohol (pva), is needed to stabilize the spion and prevent aggregation. as the particles are foreign to the body, reaction against the spion could occur. in this study we investigated the effects that spion may have on experimental arthritis after intra-articular (i.a.) or intravenous (i.v. ...	2015	25955417
a population response analysis approach to assign class ii hla-epitope restrictions.	identification of the specific hla locus and allele presenting an epitope for recognition by specific tcrs (hla restriction) is necessary to fully characterize the immune response to ags. experimental determination of hla restriction is complex and technically challenging. as an alternative, the restricting hla locus and allele can be inferred by genetic association, using response data in an hla-typed population. however, simple odds ratio (or) calculations can be problematic when dealing with ...	2015	25948811
effects of 39 compounds on calmodulin-regulated adenylyl cyclases ac1 and bacillus anthracis edema factor.	adenylyl cyclases (acs) catalyze the conversion of atp into the second messenger camp. membranous ac1 (ac1) is involved in processes of memory and learning and in muscle pain. the ac toxin edema factor (ef) of bacillus anthracis is involved in the development of anthrax. both acs are stimulated by the eukaryotic ca(2+)-sensor calmodulin (cam). the cam-ac interaction could constitute a potential target to enhance or impair the ac activity of ac1 and ef to intervene in above (patho)physiological m ...	2015	25946093
activation of the alternative pathway of complement during the acute phase of typical haemolytic uraemic syndrome.	haemolytic uraemic syndrome (hus) is characterized by haemolytic anaemia, thrombocytopenia and acute renal failure. we studied the activation state of classical and alternative pathways of complement during the acute phase of shiga toxin-associated hus by performing a prospective study of 18 patients and 17 age-matched healthy controls to evaluate c3, c3c, c4, c4d, bb and sc5b-9 levels. sc5b-9 levels were increased significantly in all patients at admission compared to healthy and end-stage rena ...	2015	25677399
a comparative clinical study to assess safety and reactogenicity of a dtwp-hepb+hib vaccine.	hepatitis b and haemophilus influenzae type b (hib) infections are major public health problems in developing countries, including india. hence, combination vaccines containing dtwp, recombinant hepatitis b and hib conjugate vaccines have been developed. here, we report a phase iv study which assessed safety and reactogenicity of a new dtwp-hepb+hib vaccine. three doses of dtwp-hepb+hib vaccine (pentavac, serum institute of india ltd) or tritanrix-hb+hib (glaxosmithkline beecham) were administer ...	2015	25933183
membrane-pore forming characteristics of the bordetella pertussis cyaa-hemolysin domain.	previously, the 126-kda bordetella pertussis cyaa pore-forming/hemolysin (cyaa-hly) domain was shown to retain its hemolytic activity causing lysis of susceptible erythrocytes. here, we have succeeded in producing, at large quantity and high purity, the his-tagged cyaa-hly domain over-expressed in escherichia coli as a soluble hemolytically-active form. quantitative assays of hemolysis against sheep erythrocytes revealed that the purified cyaa-hly domain could function cooperatively by forming a ...	2015	25941766
control of morphological differentiation of streptomyces coelicolor a3(2) by phosphorylation of mrec and pbp2.	during morphological differentiation of streptomyces coelicolor a3(2), the sporogenic aerial hyphae are transformed into a chain of more than fifty spores in a highly coordinated manner. synthesis of the thickened spore envelope is directed by the streptomyces spore wall synthesizing complex sssc which resembles the elongasome of rod-shaped bacteria. the sssc includes the eukaryotic type serine/threonine protein kinase (estpk) pkai, encoded within a cluster of five independently transcribed estp ...	2015	25927987