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complement system part ii: role in immunity.the complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. this review discusses recent advances in the understanding of the role of complement in physiology and pathology. it starts with a description of com ...201526074922
environmental phosphate differentially affects virulence phenotypes of uropathogenic escherichia coli isolates causative of prostatitis.k-12 escherichia coli cells grown in static media containing a critical phosphate (pi) concentration ≥25 mm maintained a high polyphosphate (polyp) level in stationary phase, impairing biofilm formation, a phenomenon that is triggered by polyp degradation. pi concentration in human urine fluctuates according to health state. here, the influence of environmental pi concentration on the occurrence of virulence traits in uropathogenic e. coli (upec) isolated from acute prostatitis patients was eval ...201526083279
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 ...201526085551
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 ...201526090226
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 ...201526090861
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 ...201526094775
chitosan as an adjuvant for a helicobacter pylori therapeutic vaccine.the aim of the present study was to delineate the therapeutic effect of a helicobacter pylori vaccine with chitosan as an adjuvant, as well as to identify the potential mechanism against h. pylori infection when compared with an h. pylori vaccine, with cholera toxin (ct) as an adjuvant. mice were first infected with h. pylori and, following the establishment of an effective infection model, were vaccinated using an h. pylori protein vaccine with chitosan as an adjuvant. levels of h. pylori colon ...201526095723
respiratory infection with a bacterial pathogen attenuates cns autoimmunity through il-10 induction.infection with viral or bacterial pathogens has been linked with the development of multiple sclerosis (ms), while infection with helminth parasites has been associated protection against ms and other autoimmune diseases. here we have used a murine model of ms, experimental autoimmune encephalomyelitis (eae), to examine the effect of infection with the respiratory pathogen bordetella pertussis infection on development of cns inflammation. the data demonstrate that infection of mice with b. pertu ...201526100487
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 ...201526101460
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 ...201526103968
diversity of the epsilonproteobacteria dsb (disulfide bond) systems.the bacterial proteins of the dsb family-important components of the post-translational protein modification system-catalyze the formation of disulfide bridges, a process that is crucial for protein structure stabilization and activity. dsb systems play an essential role in the assembly of many virulence factors. recent rapid advances in global analysis of bacteria have thrown light on the enormous diversity among bacterial dsb systems. while the escherichia coli disulfide bond-forming system is ...201526106374
evaluation of four commercial multiplex molecular tests for the diagnosis of acute respiratory infections.acute respiratory infections (aris) are responsible for considerable morbidity and mortality worldwide. documentation of respiratory specimens can help for an appropriate clinical management with a significant effect on the disease progress in patient, the antimicrobial therapy used and the risk of secondary spread of infection. here, we compared the performances of four commercial multiplex kits used in french university hospital diagnostic microbiology laboratories for the detection of ari pat ...201526107509
practical review of immunizations in adult patients with cancer.compared with the general population, patients with cancer in general are more susceptible to vaccine-preventable infections, either by an increased risk due to the malignancy itself or immunosuppressive treatment. the goal of immunizations in these patients is therefore to provide protection against these infections, and to decrease the number of vulnerable patients who can disseminate these organisms. the proper timing of immunization with cancer treatment is key to achieving better vaccine pr ...201526110220
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 ...201526112072
widespread bordetella parapertussis infections-wisconsin, 2011-2012: clinical and epidemiologic features and antibiotic use for treatment and prevention.during october 2011-december 2012, concurrent with a statewide pertussis outbreak, 443 bordetella parapertussis infections were reported among wisconsin residents. we examined clinical features of patients with parapertussis and the effect of antibiotic use for treatment and prevention.201526113655
the variability of the order burkholderiales representatives in the healthcare units.the order burkholderiales became more abundant in the healthcare units since the late 1970s; it is especially dangerous for intensive care unit patients and patients with chronic lung diseases. the goal of this investigation was to reveal the real variability of the order burkholderiales representatives and to estimate their phylogenetic relationships.201526114111
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 ...201526114502
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 ...201526129684
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 ...201526130851
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 ...201526130965
detection of antibodies against fimbria type 3 (fim3) is useful diagnostic assay for pertussis.isolation of bordetella pertussis and detection of the pertussis genome are not always successful because of low bacterial loads in adult patients with pertussis. antibodies against pertussis toxin (pt) are measured but have low sensitivity in vaccinated subjects. there is no reliable diagnostic method at present. in this study, a fluorescent-eia against several pertussis antigens and genome detection were investigated to establish clinical laboratory diagnostic methods for pertussis. the study ...201526134278
bisamidate prodrugs of 2-substituted 9-[2-(phosphonomethoxy)ethyl]adenine (pmea, adefovir) as selective inhibitors of adenylate cyclase toxin from bordetella pertussis.novel small-molecule agents to treat bordetella pertussis infections are highly desirable, as pertussis (whooping cough) remains a serious health threat worldwide. in this study, a series of 2-substituted derivatives of 9-[2-(phosphonomethoxy)ethyl]adenine (pmea, adefovir), in their isopropyl ester bis(l-phenylalanine) prodrug form, were designed and synthesized as potent inhibitors of adenylate cyclase toxin (act) isolated from b. pertussis. the series consists of pmea analogues bearing either ...201526136378
small protein b upregulates sensor kinase bvgs expression in aeromonas veronii.earlier studies reveal that small protein b (smpb), a class of well-conserved tmrna-binding proteins, is essential for the trans-translation process, which functions as a system for translation surveillance and ribosome rescue. here, we report a previously unrecognized mechanism by which smpb alone positively regulates the expression of a sensor kinase, bvgs, in aeromonas veronii. a reporter plasmid was constructed in which the promoter of bvgs was used to control the expression of the enhanced ...201526136727
poor memory b cell generation contributes to non-protective responses to dtap vaccine antigens in otitis-prone children.we recently identified a cohort of children with recurrent episodes of acute otitis media (aom) who fail to generate protective antibody titres to otopathogens and several vaccine antigens. in this study we determined the antibody levels against dtap vaccine antigens, diphtheria toxoid (dt), tetanus toxoid (tt) and acellular pertussis toxoid (pt) in sera from 15 stringently defined otitis-prone (sop) children and 20 non-otitis-prone (nop) children. we found significantly lower concentrations of ...201526138025
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 ...201526145788
the potential of adjuvants to improve immune responses against tdap vaccines: a preclinical evaluation of mf59 and monophosphoryl lipid a.the successful approach of combining diphtheria, tetanus and pertussis antigens into a single vaccine has become a cornerstone of immunization programs. yet, even if vaccination coverage is high, a resurgence of pertussis has been reported in many countries suggesting current vaccines may not provide adequate protection. to induce better tailored and more durable immune responses against pertussis vaccines different approaches have been proposed, including the use of novel adjuvants. licensed ap ...201526149936
identification of divergent type vi secretion effectors using a conserved chaperone domain.the type vi secretion system (t6ss) is a lethal weapon used by many bacteria to kill eukaryotic predators or prokaryotic competitors. killing by the t6ss results from repetitive delivery of toxic effectors. despite their importance in dictating bacterial fitness, systematic prediction of t6ss effectors remains challenging due to high effector diversity and the absence of a conserved signature sequence. here, we report a class of t6ss effector chaperone (tec) proteins that are required for effect ...201526150500
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 ...201526150529
within-host dynamics of infection: from ecological insights to evolutionary predictions. 201526150670
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 ...201526151934
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 ...201526152845
use of a new high resolution melting method for genotyping pathogenic leptospira spp.leptospirosis is a worldwide zoonosis that is endemic in tropical areas, such as reunion island. the species leptospira interrogans is the primary agent in human infections, but other pathogenic species, such as l. kirschner and l. borgpetersenii, are also associated with human leptospirosis.201526154161
host specificity of ovine bordetella parapertussis and the role of complement.the classical bordetellae are comprised of three subspecies that differ from broad to very limited host specificity. although several lineages appear to have specialized to particular host species, most retain the ability to colonize and grow in mice, providing a powerful common experimental model to study their differences. one of the subspecies, bordetella parapertussis, is composed of two distinct clades that have specialized to different hosts: one to humans (bpphu), and the other to sheep ( ...201526158540
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 ...201526158773
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 ...201526160169
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 ...201526163590
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 ...201526163591
structure activity characterization of bordetella petrii lipid a, from environment to human isolates.bordetella petrii, a facultative anaerobic species, is the only known member of the bordetella genus with environmental origin. however it was also recently isolated from humans. the structures of the b. petrii lipid a moieties of the endotoxins were characterized here for the first time for an environmental strain and compared to that of human isolates. characterization was achieved using chemical analyses, gas chromatography-mass spectrometry, and matrix assisted laser desorption ionisation ma ...201626164553
proteomic contributions to our understanding of vaccine and immune responses.vaccines are one of the greatest public health successes; yet, due to the empirical nature of vaccine design, we have an incomplete understanding of how the genes and proteins induced by vaccines contribute to the development of both protective innate and adaptive immune responses. while the advent of genomics has enabled new vaccine development and facilitated understanding of the immune response, proteomics identifies potentially new vaccine antigens with increasing speed and sensitivity. in a ...201526172619
a ten-year case-control study of passive smoke exposure as a risk factor for pertussis in children.the authors conducted a matched case-control study of laboratory-confirmed pertussis cases, occurring from 1/1/1996 to 12/31/2005, in children up to 12 years of age who were members of a large managed care organization. sixty-five laboratoryconfirmed cases of pertussis were identified. using multivariable conditional logistic regression analysis, the authors did not detect a statistically significant association between pertussis and household passive exposure to cigarette smoking.201526176570
isothermal detection of mycoplasma pneumoniae directly from respiratory clinical specimens.mycoplasma pneumoniae is a leading cause of community-acquired pneumonia (cap) across patient populations of all ages. we have developed a loop-mediated isothermal amplification (lamp) assay that enables rapid, low-cost detection of m. pneumoniae from nucleic acid extracts and directly from various respiratory specimen types. the assay implements calcein to facilitate simple visual readout of positive results in approximately 1 h, making it ideal for use in primary care facilities and resource-p ...201526179304
acylation of biomolecules in prokaryotes: a widespread strategy for the control of biological function and metabolic stress.acylation of biomolecules (e.g., proteins and small molecules) is a process that occurs in cells of all domains of life and has emerged as a critical mechanism for the control of many aspects of cellular physiology, including chromatin maintenance, transcriptional regulation, primary metabolism, cell structure, and likely other cellular processes. although this review focuses on the use of acetyl moieties to modify a protein or small molecule, it is clear that cells can use many weak organic aci ...201526179745
genetic variation of bordetella pertussis in austria.in austria, vaccination coverage against bordetella pertussis infections during infancy is estimated at around 90%. within the last years, however, the number of pertussis cases has increased steadily, not only in children but also in adolescents and adults, indicating both insufficient herd immunity and vaccine coverage. waning immunity in the host and/or adaptation of the bacterium to the immunised hosts could contribute to the observed re-emergence of pertussis. in this study we therefore add ...201526182210
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 ...201526184312
erratum for boinett et al., complete genome sequence of bordetella pertussis d420. 201526184951
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 ...201526185092
correlation of real time pcr cycle threshold cut-off with bordetella pertussis clinical severity.bordetella pertussis testing performed using real-time polymerase chain reaction (rt-pcr) is interpreted based on a cycle threshold (ct) value. at public health ontario laboratories (phol), a ct value <36 is reported as positive, and ct values ≥36 and <40 are reported as indeterminate. phol reported indeterminate results to physicians and public health units until may 2012, after which these results were only reported to physicians. we investigated the association between ct value and disease sy ...201526186564
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 ...201526187956
characterization of two achromobacter xylosoxidans isolates from patients with pertussis-like symptoms.to characterize two achromobacter xylosoxidans recovered from 2 patients diagnosed with pertussis during a bordetella pertussis surveillance program.201526194831
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.201526196891
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 ...201526203186
the protein bpsb is a poly-β-1,6-n-acetyl-d-glucosamine deacetylase required for biofilm formation in bordetella bronchiseptica.bordetella pertussis and bordetella bronchiseptica are the causative agents of whooping cough in humans and a variety of respiratory diseases in animals, respectively. bordetella species produce an exopolysaccharide, known as the bordetella polysaccharide (bps), which is encoded by the bpsabcd operon. bps is required for bordetella biofilm formation, colonization of the respiratory tract, and confers protection from complement-mediated killing. in this report, we have investigated the role of bp ...201526203190
cross kingdom activators of five classes of bacterial effectors. 201526203905
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 ...201526204512
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 ...201526207528
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.201526207625
seroprevalence studies of pertussis: what have we learned from different immunized populations.bordetella pertussis is a pathogen-causing whooping cough (pertussis) in humans. although vaccination against the disease is effective, the bacterium is still circulating among population and can even cause death. especially young infants, who lack protection, are vulnerable. the laboratory diagnostic methods to detect b. pertussis are culture, pcr and elisa serology. reported cases of the disease vary among countries but usually the incidence rates are low, <1 to 10/100 000. however, pertussis ...201526208655
vaccineda: prediction, design and genome-wide screening of oligodeoxynucleotide-based vaccine adjuvants.immunomodulatory oligodeoxynucleotides (imodns) are the short dna sequences that activate the innate immune system via toll-like receptor 9. these sequences predominantly contain unmethylated cpg motifs. in this work, we describe vaccineda (vaccine dna adjuvants), a web-based resource developed to design imodn-based vaccine adjuvants. we collected and analyzed 2193 experimentally validated imodns obtained from the literature. certain types of nucleotides (e.g., t, gt, tc, tt, cgt, tcg, ttt) are ...201526212482
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.201526216320
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 ...201526216418
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 ...201526216843
immune efficacy of five novel recombinant bordetella bronchiseptica proteins.the gram-negative pathogen bordetella bronchiseptica causes acute and chronic respiratory infection in a variety of animals. currently, there is no vaccine to prevent these infections. to identify useful candidate antigens for such a vaccine, five b. bronchiseptica genes including amino acid atp-binding cassette transporter substrate-binding protein (abc), lipoprotein (pl), outer membrane porin protein (ppp), leu/ile/val-binding protein (bpp), and conserved hypothetical protein (chp) were cloned ...201526223229
direct detection of erythromycin-resistant bordetella pertussis in clinical specimens by pcr.resistance of bordetella pertussis to erythromycin has been increasingly reported. we developed an allele-specific pcr method for rapid detection of erythromycin-resistant b. pertussis directly from nasopharyngeal (np) swab samples submitted for diagnostic pcr. based on the proven association of erythromycin resistance with the a2047g mutation in the 23s rrna of b. pertussis, four primers, two of which were designed to be specific for either the wild-type or the mutant allele, were used in two d ...201526224847
a case of bordetella brochiseptica at a military medical facility in hawai'i: phenotypic and molecular testing of an uncommon human pathogen.bordetella bronchiseptica (b. bronchiseptica) is rarely implicated in human disease. human infections typically occur in the context of immunosuppression and while human infection has been sporadically reported in the literature, the majority of these reports are largely descriptive and do not explore the molecular and phenotypic properties of the isolates in question. here we report the isolation and characterization of a b. bronchiseptica isolate derived from an hiv positive patient at tripler ...201526225268
genome-wide association study identifies snps in the mhc class ii loci that are associated with self-reported history of whooping cough.whooping cough is currently seeing resurgence in countries despite high vaccine coverage. there is considerable variation in subject-specific response to infection and vaccine efficacy, but little is known about the role of human genetics. we carried out a case-control genome-wide association study of adult or parent-reported history of whooping cough in two cohorts from the uk: the alspac cohort and the 1958 british birth cohort (815/758 cases and 6341/4308 controls, respectively). we also impu ...201526231221
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 ...201526232539
rapid, semiquantitative assay to discriminate among compounds with activity against replicating or nonreplicating mycobacterium tuberculosis.the search for drugs that can kill replicating and nonreplicating mycobacterium tuberculosis faces practical bottlenecks. measurement of cfu and discrimination of bacteriostatic from bactericidal activity are costly in compounds, supplies, labor, and time. testing compounds against m. tuberculosis under conditions that prevent the replication of m. tuberculosis often involves a second phase of the test in which conditions are altered to permit the replication of bacteria that survived the first ...201526239979
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 ...201526240071
t-cell immune responses to bordetella pertussis infection and vaccination.the recent immunological investigations, stemming from the studies performed in the nineties within the clinical trials of the acellular pertussis vaccines, have highlighted the important role played by t-cell immunity to pertussis in humans. these studies largely confirmed earlier investigations in the murine respiratory infection models that humoral immunity alone is not sufficient to confer protection against bordetella pertussis infection and that t-cell immunity is required. over the last y ...201526242279
bordetella pertussis, b. parapertussis, vaccines and cycles of whooping cough.whooping cough is a vaccine-preventable disease due to bordetella pertussis and b. parapertussis. this highly contagious respiratory disease occurs through epidemic cycles every 3-5 years and vaccination did not change this frequency. models suggest that the cyclic increase of susceptibles is linked to demographic differences and different vaccine coverage. however, differences in surveillance of the disease as well as adaptation of the agents of the disease to their human hosts and to vaccine p ...201526242280
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 ...201526243660
the bordetella secreted regulator bspr is translocated into the nucleus of host cells via its n-terminal moiety: evaluation of bacterial effector translocation by the escherichia coli type iii secretion system.bordetella bronchiseptica is genetically related to b. pertussis and b. parapertussis, which cause respiratory tract infections in humans. these pathogens possess a large number of virulence factors, including the type iii secretion system (t3ss), which is required for the delivery of effectors into the host cells. in a previous study, we identified a transcriptional regulator, bspr, that is involved in the regulation of the t3ss-related genes in response to iron-starved conditions. a unique fea ...201526247360
interactions between autophagy and bacterial toxins: targets for therapy?autophagy is a physiological process involved in defense mechanisms for clearing intracellular bacteria. the autophagic pathway is finely regulated and bacterial toxins interact with this process in a complex manner. bacterial toxins also interact significantly with many biochemical processes. evaluations of the effects of bacterial toxins, such as endotoxins, pore-forming toxins and adenylate cyclases, on autophagy could support the development of new strategies for counteracting bacterial path ...201526248079
role of interleukin-12 in protection against pulmonary infection with methicillin-resistant staphylococcus aureus.methicillin-resistant staphylococcus aureus (mrsa) is a common pathogen associated with nosocomial pneumonia and is an increasing threat for severe community-acquired pneumonia. we have now investigated the role of interleukin-12 (il-12) in protective immunity against lung infection with mrsa. the importance of il-12 in protection from pulmonary mrsa infection was demonstrated by the finding that il-12p35-deficient mice had a lower survival rate, higher bacterial burdens in lung and spleen, and ...201526248370
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 ...201526253079
the efficacy of qingfengganke granule in treating postinfectious cough in pathogenic wind invading lungs syndrome: a multicenter, randomized, double-blind, placebo-controlled trial.postinfectious cough (pic) significantly affects cough-related quality of life but still lacks effective treatments. this study aims to investigate the efficacy of qingfengganke granule (qfgkg) in treating pic induced by pathogenic wind invading lungs syndrome.201526257822
strategies and new developments to control pertussis, an actual health problem.the aim of this article is to describe the current epidemiological situation of pertussis, as well as different short-term strategies that have been implemented to alleviate this threat. the state of the art of the development of new vaccines that are expected to provide long-lasting immunity against pertussis was also included.201526260328
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 ...201526260457
virulence factors variation among bordetella pertussis isolates in iran. 201526261803
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.201526265208
insights into the respiratory tract microbiota of patients with cystic fibrosis during early pseudomonas aeruginosa colonization.pseudomonas aeruginosa plays a major role in cystic fibrosis (cf) progression. therefore, it is important to understand the initial steps of p. aeruginosa infection. the structure and dynamics of cf respiratory tract microbial communities during the early stages of p. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. the respiratory microbiota showed high diversity, related to the young age of the cf cohort (mean age 10 years). wide inter- and intra-individual ...201526266076
applications of bacillus calmette-guerin and recombinant bacillus calmette-guerin in vaccine development and tumor immunotherapy.bacillus calmette-guerin (bcg) vaccines are attenuated live strains of mycobacterium bovis and are among the most widely used vaccines in the world. bcg is proven to be effective in preventing severe infant meningitis and miliary tuberculosis. intravesical instillation of bcg is also a standard treatment for non-muscle invasive bladder cancer. in the past few decades, recombinant bcg (rbcg) technology had been extensively applied to develop vaccine candidates for a variety of infectious diseases ...201526268434
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 ...201526271954
frequency and characteristics of hospital-sponsored pertussis revaccination programs in the southern united states.the centers for disease control and prevention (cdc) released guidelines in december, 2006, recommending revaccination against bordetella pertussis with tdap for all post-partum women and healthcare workers. the cdc recommendations specifically state "the postpartum tdap should be administered before discharge from the hospital or birthing center" and "hospitals and ambulatory-care facilities should provide tdap for healthcare personnel." the purpose of this survey was to determine the frequency ...201526272891
phylogenetic and amino acid conservation analyses of bacterial l-aspartate-α-decarboxylase and of its zymogen-maturation protein reveal a putative interaction domain.all organisms must synthesize the enzymatic cofactor coenzyme a (coa) from the precursor pantothenate. most bacteria can synthesize pantothenate de novo by the condensation of pantoate and β-alanine. the synthesis of β-alanine is catalyzed by l-aspartate-α-decarboxylase (pand), a pyruvoyl enzyme that is initially synthesized as a zymogen (pro-pand). active pand is generated by self-cleavage of pro-pand at gly24-ser25 creating the active-site pyruvoyl moiety. in salmonella enterica, this cleavage ...201526276430
estimated and reported incidence of pertussis in estonian adults: a seroepidemiological study.rates of pertussis immunisation among children in estonia are high (∼95%), but pertussis is still the most common vaccine preventable childhood disease. adults are suspected to be sources of pertussis in children. we aimed to measure pertussis toxin (pt) igg in adults to estimate pertussis infection activity and compare estimated and reported pertussis incidences.201526277068
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 ...201526278132
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 ...201526283022
new insight into filamentous hemagglutinin secretion reveals a role for full-length fhab in bordetella virulence.bordetella filamentous hemagglutinin (fha), a primary component of acellular pertussis vaccines, contributes to virulence, but how it functions mechanistically is unclear. fha is first synthesized as an ~370-kda preproprotein called fhab. removal of an n-terminal signal peptide and a large c-terminal prodomain (pd) during secretion results in "mature" ~250-kda fha, which has been assumed to be the biologically active form of the protein. deletion of two c-terminal subdomains of fhab did not affe ...201526286694
cultivation of an adaptive domestic network for surveillance and evaluation of emerging infections.accomplishments of this program have provided numerous dividends and might benefit areas outside infectious diseases.201526289824
detection and characterization of respiratory viruses causing acute respiratory illness and asthma exacerbation in children during three different season (2011-2014) in mexico city.viral infections play a significant role as cause of acute respiratory infections (aris) and exacerbations of chronic diseases. aris are now the leading cause of mortality in children worldwide, especially in developing countries. recently human rhinovirus (hrv) infection has been emerged as an important cause of pneumonia and asthma exacerbation.201526289993
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 ...201526291475
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 ...201526291642
effect of culture-independent diagnostic tests on future emerging infections program surveillance.the centers for disease control and prevention emerging infections program (eip) network conducts population-based surveillance for pathogens of public health importance. central to obtaining estimates of disease burden and tracking microbiological characteristics of these infections is accurate laboratory detection of pathogens. the use of culture-independent diagnostic tests (cidts) in clinical settings presents both opportunities and challenges to eip surveillance. because cidts offer better ...201526291736
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 ...201526291883
a thiol-disulfide oxidoreductase of the gram-positive pathogen corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence.the gram-positive pathogen corynebacterium diphtheriae exports through the sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. how these proteins attain their native conformations after translocation as unfolded precursors remains elusive. the fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the ...201526294390
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 ...201526296891
bordetella pertussis evolution in the (functional) genomics era.the incidence of whooping cough caused by bordetella pertussis in many developed countries has risen dramatically in recent years. this has been linked to the use of an acellular pertussis vaccine. in addition, it is thought that b. pertussis is adapting under acellular vaccine mediated immune selection pressure, towards vaccine escape. genomics-based approaches have revolutionized the ability to resolve the fine structure of the global b. pertussis population and its evolution during the era of ...201526297914
beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold.for the past 25 years, phage display technology has been an invaluable tool for studies of protein-protein interactions. however, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. this review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. part ...201526300850
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 ...201526302243
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