Publications

pore forming activity of the potent rtx-toxin produced by pediatric pathogen kingella kingae: characterization and comparison to other rtx-family members.	pediatric septic arthritis in patients under age of four is frequently caused by the oral gram-negative bacterium kingella kingae. this organism may be responsible for a severe form of infective endocarditis in otherwise healthy children and adults. a major virulence factor of k. kingae is rtxa, a toxin that belongs to the rtx (repeats-in-toxin) group of secreted pore forming toxins. to understand the rtxa effects on host cell membranes, the toxin activity was studied using planar lipid bilayers ...	2015	25858109
importance of enhanced surveillance for prevention of pertussis in children.	bordetella pertussis infection causes considerable morbidity, even in countries with high vaccination coverage. surveillance of pertussis is usually passive and based on mandatory reporting. we assessed the epidemiologic and clinical characteristics of pertussis cases detected by passive or enhanced surveillance.	2015	25860533
molecular epidemiology of bordetella pertussis in the philippines in 2012-2014.	the present study was designed to determine the genotypes of circulating bordetella pertussis in the philippines by direct molecular typing of clinical specimens.	2015	25861926
development and validation of a broad scheme for prediction of hla class ii restricted t cell epitopes.	computational prediction of hla class ii restricted t cell epitopes has great significance in many immunological studies including vaccine discovery. in recent years, prediction of hla class ii binding has improved significantly but a strategy to globally predict the most dominant epitopes has not been rigorously defined. using human immunogenicity data associated with sets of 15-mer peptides overlapping by 10 residues spanning over 30 different allergens and bacterial antigens, and hla class ii ...	2015	25862607
bordetella pertussis infection among international travellers: the need for a rigorous implementation of vaccine policies.		2015	25864792
engineered nanoparticles mimicking cell membranes for toxin neutralization.	protein toxins secreted from pathogenic bacteria and venomous animals rely on multiple mechanisms to overcome the cell membrane barrier to inflict their virulence effect. a promising therapeutic concept toward developing a broadly applicable anti-toxin platform is to administer cell membrane mimics as decoys to sequester these virulence factors. as such, lipid membrane-based nanoparticulates are an ideal candidate given their structural similarity to cellular membranes. this article reviews the ...	2015	25868452
multiplex real-time pcr assay for detection and differentiation of bordetella pertussis and bordetella parapertussis.	rapid diagnosis of pertussis is important for the timely isolation of the infection source and early prevention measures among the contact persons, especially among non-vaccinated infants for whom pertussis is life-threatening.	2014	25870746
minimum inhibitory concentrations of erythromycin and other antibiotics for czech strains of bordetella pertussis.	to test the susceptibility to first-line and alternative antibiotics of 70 bordetella pertussis (b. pertussis) strains recovered from patients with whooping cough through national pertussis surveillance in the czech republic (cr) in 1967-2010.	2015	25872990
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
pertussis prevalence and its determinants among children with persistent cough in urban uganda.	we determined prevalence of pertussis infection and its associated host and environmental factors to generate information that would guide strategies for disease control.	2015	25874411
bordetella pertussis adenylate cyclase toxin blocks induction of bactericidal nitric oxide in macrophages through camp-dependent activation of the shp-1 phosphatase.	the adenylate cyclase toxin-hemolysin (cyaa) plays a key role in the virulence of bordetella pertussis. cyaa penetrates complement receptor 3-expressing phagocytes and catalyzes uncontrolled conversion of cytosolic atp to the key second messenger molecule camp. this paralyzes the capacity of neutrophils and macrophages to kill bacteria by complement-dependent oxidative burst and opsonophagocytic mechanisms. we show that camp signaling through the protein kinase a (pka) pathway activates src homo ...	2015	25876760
dose-response models for selected respiratory infectious agents: bordetella pertussis, group a streptococcus, rhinovirus and respiratory syncytial virus.	dose-response assessment is one step in quantitative microbial risk assessment (qmra). four infectious microbes capable of causing respiratory diseases important to public health, and for which dose-response functions have not been available are: bordetella pertussis (whooping cough), group a streptococcus (pharyngitis), rhinovirus (common cold) and respiratory syncytial virus (common cold). the objective of this study was to fit dose-response functions for these microbes to published experiment ...	2015	25880210
local hopping mobile dna implicated in pseudogene formation and reductive evolution in an obligate cyanobacteria-plant symbiosis.	insertion sequences (iss) are approximately 1 kbp long "jumping" genes found in prokaryotes. iss encode the protein transposase, which facilitates the excision and reinsertion of iss in genomes, making these sequences a type of class i ("cut-and-paste") mobile genetic elements. iss are proposed to be involved in the reductive evolution of symbiotic prokaryotes. our previous sequencing of the genome of the cyanobacterium 'nostoc azollae' 0708, living in a tight perpetual symbiotic association wit ...	2015	25885210
endotracheal tube biofilm translocation in the lateral trendelenburg position.	laboratory studies demonstrated that the lateral trendelenburg position (ltp) is superior to the semirecumbent position (srp) in the prevention of ventilator-associated pulmonary infections. we assessed whether the ltp could also prevent pulmonary colonization and infections caused by an endotracheal tube (ett) biofilm.	2015	25887536
etiology of community-acquired pneumonia and diagnostic yields of microbiological methods: a 3-year prospective study in norway.	despite recent advances in microbiological techniques, the etiology of community-acquired pneumonia (cap) is still not well described. we applied polymerase chain reaction (pcr) and conventional methods to describe etiology of cap in hospitalized adults and evaluated their respective diagnostic yields.	2015	25887603
identification of viral and bacterial pathogens from hospitalized children with severe acute respiratory illness in lusaka, zambia, 2011-2012: a cross-sectional study.	morbidity and mortality from respiratory infections are higher in resource-limited countries than developed countries, but limited studies have been conducted in resource-limited settings to examine pathogens from patients with acute respiratory infections. influenza surveillance has been conducted in zambia since 2008; however, only 4.3% of patients enrolled in 2011-2012 were positive for influenza. therefore, we examined non-influenza respiratory pathogens in children with severe acute respira ...	2015	25888024
combination vaccines against diarrheal diseases.	diarrheal diseases remain a leading cause of global childhood mortality and morbidity. several recent epidemiological studies highlight the rate of diarrheal diseases in different parts of the world and draw attention to the impact on childhood growth and survival. despite the well-documented global burden of diarrheal diseases, currently there are no combination diarrheal vaccines, only licensed vaccines for rotavirus and cholera, and salmonella typhi-based vaccines for typhoid fever. the recog ...	2015	25891647
transcriptomic analysis of yersinia enterocolitica biovar 1b infecting murine macrophages reveals new mechanisms of extracellular and intracellular survival.	yersinia enterocolitica is typically considered an extracellular pathogen; however, during the course of an infection, a significant number of bacteria are stably maintained within host cell vacuoles. little is known about this population and the role it plays during an infection. to address this question and to elucidate the spatially and temporally dynamic gene expression patterns of y. enterocolitica biovar 1b through the course of an in vitro infection, transcriptome sequencing and different ...	2015	25895974
a change in vaccine efficacy and duration of protection explains recent rises in pertussis incidence in the united states.	over the past ten years the incidence of pertussis in the united states (u.s.) has risen steadily, with 2012 seeing the highest case number since 1955. there has also been a shift over the same time period in the age group reporting the largest number of cases (aside from infants), from adolescents to 7-11 year olds. we use epidemiological modelling and a large case incidence dataset to explain the upsurge. we investigate several hypotheses for the upsurge in pertussis cases by fitting a suite o ...	2015	25906150
spatio-temporal remodeling of functional membrane microdomains organizes the signaling networks of a bacterium.	lipid rafts are membrane microdomains specialized in the regulation of numerous cellular processes related to membrane organization, as diverse as signal transduction, protein sorting, membrane trafficking or pathogen invasion. it has been proposed that this functional diversity would require a heterogeneous population of raft domains with varying compositions. however, a mechanism for such diversification is not known. we recently discovered that bacterial membranes organize their signal transd ...	2015	25909364
recommendation for a standardised method of broth microdilution susceptibility testing for porcine bordetella bronchiseptica.	the objective was to establish and standardise a broth microdilution susceptibility testing method for porcine bordetella (b.) bronchiseptica. b. bronchiseptica isolates from different geographical regions and farms were genotyped by macrorestriction analysis and subsequent pulsed-field gel electrophoresis. one reference and one type strain plus two field isolates of b. bronchiseptica were chosen to analyse growth curves in four different media: cation-adjusted mueller-hinton broth (camhb) with ...	2015	25910232
serum procalcitonin measurement and viral testing to guide antibiotic use for respiratory infections in hospitalized adults: a randomized controlled trial.	viral lower respiratory tract illness (lrti) frequently causes adult hospitalization and is linked to antibiotic overuse. european studies suggest that the serum procalcitonin (pct) level may be used to guide antibiotic therapy. we conducted a trial assessing the feasibility of using pct algorithms with viral testing to guide antibiotic use in a us hospital.	2015	25910632
prevention of pertussis through adult vaccination.	pertussis is a vaccine preventable respiratory infection. young infants are at high risk of developing severe complications from infection. despite high rates of pediatric vaccine uptake, there continues to be increases in pertussis cases, likely due to waning immunity from childhood vaccine and increased transmission through adults. currently, pertussis booster vaccine (tdap) is recommended for unimmunized adults and for women in the third trimester of each pregnancy; yet adult tdap coverage re ...	2015	25912733
bordetella pertussis infection in paediatric healthcare workers.	an increased incidence of pertussis has been observed recently in adults, and healthcare workers (hcws) are considered a risk group for transmission to infants. prevalence of recent pertussis infection was assessed in hcws from a paediatric department of a tertiary care hospital in brazil. serum pertussis toxin igg antibodies were measured by enzyme-linked immunosorbent assay. of 388 hcws included in the analysis, 6.4% had serology suggestive of recent infection. medical residents [odds ratio (o ...	2015	25913647
novel role for pilno in type iv pilus retraction revealed by alignment subcomplex mutations.	type iv pili (t4p) are dynamic protein filaments that mediate bacterial adhesion, biofilm formation, and twitching motility. the highly conserved pilmnop proteins form an inner membrane alignment subcomplex required for function of the t4p system, though their exact roles are unclear. three potential interaction interfaces for pilno were identified: core-core, coiled coils (cc), and the transmembrane segments (tmss). a high-confidence pilno heterodimer model was used to select key residues for m ...	2015	25917913
murj and a novel lipid ii flippase are required for cell wall biogenesis in bacillus subtilis.	bacterial surface polysaccharides are synthesized from lipid-linked precursors at the inner surface of the cytoplasmic membrane before being translocated across the bilayer for envelope assembly. transport of the cell wall precursor lipid ii in escherichia coli requires the broadly conserved and essential multidrug/oligosaccharidyl-lipid/polysaccharide (mop) exporter superfamily member murj. here, we show that bacillus subtilis cells lacking all 10 mop superfamily members are viable with only mi ...	2015	25918422
development and characterization of an effective food allergy model in brown norway rats.	food allergy (fa) is an adverse health effect produced by the exposure to a given food. currently, there is no optimal animal model of fa for the screening of immunotherapies or for testing the allergenicity of new foods.	2015	25923134
treatment with 1,25(oh)2d3 induced hdac2 expression and reduced nf-κb p65 expression in a rat model of ova-induced asthma.	recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin d3 (1,25[oh]2d3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. we aimed to investigate the effect of 1,25(oh)2d3 on the expression and enzyme activity of histone deacetylase 2 (hdac2) and its synergistic effects with dexamethasone (dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. healthy wistar rats were randomly div ...	2015	25923460
stable expression of lentiviral antigens by quality-controlled recombinant mycobacterium bovis bcg vectors.	the well-established safety profile of the tuberculosis vaccine strain, mycobacterium bovis bacille calmette-guérin (bcg), makes it an attractive vehicle for heterologous expression of antigens from clinically relevant pathogens. however, successful generation of recombinant bcg strains possessing consistent insert expression has encountered challenges in stability. here, we describe a method for the development of large recombinant bcg accession lots which stably express the lentiviral antigens ...	2015	25924766
mechanisms of antimicrobial peptide resistance in gram-negative bacteria.	cationic antimicrobial peptides (camps) are important innate immune defenses that inhibit colonization by pathogens and contribute to clearance of infections. gram-negative bacterial pathogens are a major target, yet many of them have evolved mechanisms to resist these antimicrobials. these resistance mechanisms can be critical contributors to bacterial virulence and are often crucial for survival within the host. here, we summarize methods used by gram-negative bacteria to resist camps. underst ...	2014	25927010
mechanisms of antimicrobial peptide resistance in gram-negative bacteria.	cationic antimicrobial peptides (camps) are important innate immune defenses that inhibit colonization by pathogens and contribute to clearance of infections. gram-negative bacterial pathogens are a major target, yet many of them have evolved mechanisms to resist these antimicrobials. these resistance mechanisms can be critical contributors to bacterial virulence and are often crucial for survival within the host. here, we summarize methods used by gram-negative bacteria to resist camps. underst ...	2014	25927010
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
the burden of pertussis in low- and middle-income countries since the inception of the expanded programme on immunization (epi) in 1974: a systematic review protocol.	vaccine against pertussis has been in use for several decades. despite the widespread use of pertussis vaccine, evidence shows resurgence of pertussis in high-income countries. pertussis surveillance data is largely missing from low- and middle-income countries (lmics). without data on trends of pertussis, it is difficult to review and amend pertussis control policies in any country. we propose conducting a systematic review to evaluate the burden and trends of pertussis in lmics since 1974.	2015	25930111
the mechanisms of action of vaccines containing aluminum adjuvants: an in vitro vs in vivo paradigm.	adjuvants such as the aluminum compounds (alum) have been dominantly used in many vaccines due to their immunopotentiation and safety records since 1920s. however, how these mineral agents influence the immune response to vaccination remains elusive. many hypotheses exist as to the mode of action of these adjuvants, such as depot formation, antigen (ag) targeting, and the induction of inflammation. these hypotheses are based on many in vitro and few in vivo studies. understanding how cells inter ...	2015	25932368
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
bacterial pathogens and community composition in advanced sewage treatment systems revealed by metagenomics analysis based on high-throughput sequencing.	this study used 454 pyrosequencing, illumina high-throughput sequencing and metagenomic analysis to investigate bacterial pathogens and their potential virulence in a sewage treatment plant (stp) applying both conventional and advanced treatment processes. pyrosequencing and illumina sequencing consistently demonstrated that arcobacter genus occupied over 43.42% of total abundance of potential pathogens in the stp. at species level, potential pathogens arcobacter butzleri, aeromonas hydrophila a ...	2015	25938416
altered β1-3-adrenoceptor influence on α2-adrenoceptor-mediated control of catecholamine release and vascular tension in hypertensive rats.	α2- and β-adrenoceptors (ar) reciprocally control catecholamine release and vascular tension. disorders in these functions are present in spontaneously hypertensive rats (shr). the present study tested if α2ar dysfunctions resulted from altered α2ar/βar interaction. blood pressure (bp) was recorded through a femoral artery catheter and cardiac output by an ascending aorta flow probe. total peripheral vascular resistance (tpr) was calculated. norepinephrine release was stimulated by a 15-min tyra ...	2015	25941491
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
cross-species chimeras reveal bama potra and β-barrel domains must be fine-tuned for efficient omp insertion.	bam is a conserved molecular machine, the central component of which is bama. orthologues of bama are found in all gram-negative bacteria, chloroplasts and mitochondria where it is required for the folding and insertion of β-barrel containing integral outer membrane proteins (omps) into the outer membrane. bama binds unfolded β-barrel precursors via the five polypeptide transport-associated (potra) domains at its n-terminus. the c-terminus of bama folds into a β-barrel domain, which tethers bama ...	2015	25943387
new players in the toxin field: polymorphic toxin systems in bacteria.	bacteria have evolved numerous strategies to increase their competitiveness and fight against each other. indeed, a large arsenal of antibacterial weapons is available in order to inhibit the proliferation of competitor cells. polymorphic toxin systems (pts), recently identified by bioinformatics in all major bacterial lineages, correspond to such a system primarily involved in conflict between related bacterial strains. they are typically composed of a secreted multidomain toxin, a protective i ...	2015	25944858
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
structural and functional studies of bapc protein of bordetella pertussis.	bordetella pertussis, the causative agent of whooping cough, attaches to mucosal surface in upper respiratory tract, where it produces a variety of surface associated and secreted autotransporter molecules among others. in this study we have cloned newly identified member of autotransporter family bapc (b. pertussis autotransporter protein c); expressed it in escherichia coli and characterized it for its different properties. we have also raised antisera to bapc protein; the antisera were used i ...	2015	25946329
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
genetic analysis, structural modeling, and direct coupling analysis suggest a mechanism for phosphate signaling in escherichia coli.	proper phosphate signaling is essential for robust growth of escherichia coli and many other bacteria. the phosphate signal is mediated by a classic two component signal system composed of phor and phob. the phor histidine kinase is responsible for phosphorylating/dephosphorylating the response regulator, phob, which controls the expression of genes that aid growth in low phosphate conditions. the mechanism by which phor receives a signal of environmental phosphate levels has remained elusive. a ...	2015	25953406
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
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
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
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
host-pathogen interaction during bacterial vaccination.	vaccines have been developed and deployed against several important bacterial pathogens of humans, including neisseria meningitidis, bordetella pertussis, streptococcus pneumoniae and mycobacterium tuberculosis. these vaccines are generally considered a successful public health measure and are effective at controlling disease symptoms and/or burden. however, a troubling consequence of recent vaccination programs has been the selection of vaccine escape mutants, whereby the pathogen displays a di ...	2015	25966310
pertussis resurgence associated with pertactin-deficient and genetically divergent bordetella pertussis isolates in israel.	the bordetella pertussis polymerase chain reaction positivity rate changed after additional diphtheria-tetanus-acellular pertussis boosters in 2005 and 2008, 9.8%, 13.4%, 22% and 15.2% in 2010, 2011, 2012 and 2013, p < 0.001, respectively. new pulsed-field gel electrophoresis profiles were detected between 2009 and 2012. the proportion of pertactin-deficient isolates increased over time, 6.6% versus 7.1% versus 33.3% during 2005-2006, 2011-2012 and 2013-2014, p < 0.03, respectively.	2015	25966915
experimental autoimmune encephalomyelitis development is aggravated by candida albicans infection.	multiple sclerosis (ms) is an inflammatory/autoimmune disease of the central nervous system (cns) mainly mediated by myelin specific t cells. it is widely believed that environmental factors, including fungal infections, contribute to disease induction or evolution. even though candida infection among ms patients has been described, the participation of this fungus in this pathology is not clear. the purpose of this work was to evaluate the effect of a candida albicans infection on experimental ...	2015	25969836
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
host cell type-dependent translocation and phop-mediated positive regulation of the effector ssek1 of salmonella enterica.	salmonella enterica expresses two virulence-related type iii secretion systems (t3sss) encoded in salmonella pathogenicity island 1 (spi1) and spi2, respectively. ssek1 is a poorly characterized substrate of the spi2-encoded t3ss. here, we show that this effector is essential to get full virulence both in oral and intraperitoneal mice infections, in spite of not having a role in invasion or intracellular proliferation in cultured mammalian cells. in vitro, expression of ssek1 was higher in media ...	2015	25972862
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
development of two real-time multiplex pcr assays for the detection and quantification of eight key bacterial pathogens in lower respiratory tract infections.	the frequent lack of a positive and timely microbiological diagnosis in patients with lower respiratory tract infection (lrti) is an important obstacle to antimicrobial stewardship. patients are typically prescribed broad-spectrum empirical antibiotics while microbiology results are awaited, but, because these are often slow, negative, or inconclusive, de-escalation to narrow-spectrum agents rarely occurs in clinical practice. the aim of this study was to develop and evaluate two multiplex real- ...	2015	25980353
viral and atypical bacterial aetiologies of infection in hospitalised patients admitted with clinical suspicion of influenza in thailand, vietnam and indonesia.	influenza constitutes a leading cause of morbidity and mortality worldwide. there is limited information about the etiology of infection presenting clinically as influenza in hospitalized adults and children in southeast asia. such data are important for future management of respiratory infections.	2015	25980749
an sos regulon under control of a noncanonical lexa-binding motif in the betaproteobacteria.	the sos response is a transcriptional regulatory network governed by the lexa repressor that activates in response to dna damage. in the betaproteobacteria, lexa is known to target a palindromic sequence with the consensus sequence ctgt-n8-acag. we report the characterization of a lexa regulon in the iron-oxidizing betaproteobacterium sideroxydans lithotrophicus. in silico and in vitro analyses show that lexa targets six genes by recognizing a binding motif with the consensus sequence gaacgaacgt ...	2015	25986903
pneumonia outbreak caused by chlamydophila pneumoniae among us air force academy cadets, colorado, usa.	during october 2013-may 2014, there were 102 cases of pneumonia diagnosed in us air force academy cadets. a total of 73% of tested nasal washes contained chlamydophila pneumoniae. this agent can be considered to be present on campus settings during outbreaks with numerous, seemingly disconnected cases of relatively mild pneumonia.	2015	25988545
immunoproteomic profiling of bordetella pertussis outer membrane vesicle vaccine reveals broad and balanced humoral immunogenicity.	the current resurgence of whooping cough is alarming, and improved pertussis vaccines are thought to offer a solution. outer membrane vesicle vaccines (omvpv) are potential vaccine candidates, but omvpv-induced humoral responses have not yet been characterized in detail. the purpose of this study was to determine the antigen composition of omvpv and to elucidate the immunogenicity of the individual antigens. quantitative proteome analysis revealed the complex composition of omvpv. the omvpv immu ...	2015	25988566
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
cough: neurophysiology, methods of research, pharmacological therapy and phonoaudiology.	the cough is the more common respiratory symptom in children and adults.	2012	25991944
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
the autotransporter bpab contributes to the virulence of burkholderia mallei in an aerosol model of infection.	burkholderia mallei is a highly pathogenic bacterium that causes the zoonosis glanders. previous studies indicated that the genome of the organism contains eight genes specifying autotransporter proteins, which are important virulence factors of gram-negative bacteria. in the present study, we report the characterization of one of these autotransporters, bpab. database searches identified the bpab gene in ten b. mallei isolates and the predicted proteins were 99-100% identical. comparative seque ...	2015	25993100
characterization of francisella tularensis schu s4 mutants identified from a transposon library screened for o-antigen and capsule deficiencies.	the lipopolysaccharide (lps) and o-antigen polysaccharide capsule structures of francisella tularensis play significant roles in helping these highly virulent bacteria avoid detection within a host. we previously created pools of f. tularensis mutants that we screened to identify strains that were not reactive to a monoclonal antibody to the o-antigen capsule. to follow up previously published work, we characterize further seven of the f. tularensis schu s4 mutant strains identified by our scree ...	2015	25999917
the primate autoimmune encephalomyelitis model; a bridge between mouse and man.	multiple sclerosis (ms) is an enigmatic autoimmune-driven inflammatory/demyelinating disease of the human central nervous system (cns), affecting brain, spinal cord, and optic nerves. the cause of the disease is not known and the number of effective treatments is limited. despite some clear successes, translation of immunological discoveries in the mouse experimental autoimmune encephalomyelitis (eae) model into effective therapies for ms patients has been difficult. this translation gap between ...	2015	26000330
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
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
a versatile, non genetically modified organism (gmo)-based strategy for controlling low-producer mutants in bordetella pertussis cultures using antigenic modulation.	the uncontrolled presence of non-producer mutants negatively affects bioprocesses. in bordetella pertussis cultures, avirulent mutants emerge spontaneously and accumulate. we characterized the dynamics of accumulation using high-throughput growth assays and competition experiments between virulent and avirulent (bvg(-) ) isolates. a fitness advantage of bvg(-) cells was identified as the main driver for bvg(-) accumulation under conditions of high virulence factor production. conversely, under c ...	2015	26014907
cooperative roles for fimbria and filamentous hemagglutinin in bordetella adherence and immune modulation.	bordetella fimbriae (fim) are generally considered to function as adhesins despite a lack of experimental evidence supporting this conclusion for bordetella pertussis and evidence against a requirement for fim in adherence of bordetella bronchiseptica to mammalian cell lines. using b. bronchiseptica and mice, we developed an in vivo adherence assay that revealed that fim do function as critically important adhesins in the lower respiratory tract. in the first few days postinoculation, fim-defici ...	2015	26015497
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
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
host antimicrobial peptides in bacterial homeostasis and pathogenesis of disease.	innate immune responses function as a first line of host defense against the development of bacterial infection, and in some cases to preserve the sterility of privileged sites in the human host. bacteria that enter these sites must counter host responses for colonization. from the host's perspective, the innate immune system works expeditiously to minimize the bacterial threat before colonization and subsequent dysbiosis. the multifactorial nature of disease further challenges predictions of ho ...	2014	26029470
the obstructive siblings: relapsing polychondritis without chondritis?	progressive narrowing of the central airways due to diffuse inflammation is a potential life-threatening condition. a number of diseases have been described as possible causes. we present two siblings with severe central airway obstruction. despite considerable efforts we have not been able to match the clinical appearance of our patients with the diagnostic criteria of any of the disease entities known to cause this condition.	2013	26029500
competition, coinfection and strain replacement in models of bordetella pertussis.	pertussis, or whooping cough, is an important respiratory infection causing considerable infant mortality worldwide. recently, incidence has risen in countries with strong vaccine programmes and there are concerns about antigenic shift resulting in vaccine evasion. interactions between pertussis and non-vaccine-preventable strains will play an important role in the evolution and population dynamics of pertussis. in particular, if we are to understand the role strain replacement plays in vaccinat ...	2015	26032910
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
vitamin d every day to keep the infection away?	within the last decade, vitamin d has emerged as a central regulator of host defense against infections. in this regard, vitamin d triggers effective antimicrobial pathways against bacterial, fungal and viral pathogens in cells of the human innate immune system. however, vitamin d also mediates potent tolerogenic effects: it is generally believed that vitamin d attenuates inflammation and acquired immunity, and thus potentially limits collateral tissue damage. nevertheless, several studies indic ...	2015	26035244
monoclonal antibody combinations that present synergistic neutralizing activity: a platform for next-generation anti-toxin drugs.	monoclonal antibodies (mabs) are among the fastest-growing therapeutics and are being developed for a broad range of indications, including the neutralization of toxins, bacteria and viruses. nevertheless, mabs potency is still relatively low when compared to conventional polyclonal ab preparations. moreover, the efficacy of an individual neutralizing mab may significantly be hampered by the potential absence or modification of its target epitope in a mutant or subtype of the infectious agent. t ...	2015	26035486
the fibronectin-binding motif within flpa facilitates campylobacter jejuni adherence to host cell and activation of host cell signaling.	campylobacter jejuni is a gram-negative, curved and rod-shaped bacterium that causes human gastroenteritis. acute disease is associated with c. jejuni invasion of the intestinal epithelium. epithelial cells infected with c. jejuni strains containing mutations in the flpa and cadf fibronectin (fn)-binding proteins exhibit reduced invasion of host cells and a c. jejuni cadf flpa double mutant is impaired in the activation of epidermal growth factor receptor (egfr) and rho gtpase rac1. although the ...	2013	26038437
pathogen-host-environment interplay and disease emergence.	gaining insight in likely disease emergence scenarios is critical to preventing such events from happening. recent focus has been on emerging zoonoses and on identifying common patterns and drivers of emerging diseases. however, no overarching framework exists to integrate knowledge on all emerging infectious disease events. here, we propose such a conceptual framework based on changes in the interplay of pathogens, hosts and environment that lead to the formation of novel disease patterns and p ...	2013	26038452
molecular basis of host specificity in human pathogenic bacteria.	pathogenic bacteria display various levels of host specificity or tropism. while many bacteria can infect a wide range of hosts, certain bacteria have strict host selectivity for humans as obligate human pathogens. understanding the genetic and molecular basis of host specificity in pathogenic bacteria is important for understanding pathogenic mechanisms, developing better animal models and designing new strategies and therapeutics for the control of microbial diseases. the molecular mechanisms ...	2014	26038515
the vaccine potential of bordetella pertussis biofilm-derived membrane proteins.	pertussis is an infectious respiratory disease of humans caused by the gram-negative pathogen bordetella pertussis. the use of acellular pertussis vaccines (aps) which induce immunity of relative short duration and the emergence of vaccine-adapted strains are thought to have contributed to the recent resurgence of pertussis in industrialized countries despite high vaccination coverage. current pertussis vaccines consist of antigens derived from planktonic bacterial cultures. however, recent stud ...	2014	26038752
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
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
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
a fusion protein derived from moraxella catarrhalis and neisseria meningitidis aimed for immune modulation of human b cells.	moraxella igd-binding protein (mid) is a well characterized trimeric autotransporter that specifically targets the igd of b cells. we fused the membrane anchor of the meningococcal autotransporter nhha with the igd-binding region of mid (aa 962-1200) to create a chimeric protein designated as nid. the aim was to use this specific targeting to provide a better vaccine candidate against meningococci, in particular serogroup b by enhancing the immunogenicity of nhha. nid was thereafter recombinantl ...	2015	26042357
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
whooping cough, twenty years from acellular vaccines introduction.	clinical pertussis resulting from infection with b. pertussis is a significant medical and public health problem, despite the huge success of vaccination that has greatly reduced its incidence. the whole cell vaccine had an undeniable success over the last 50 years, but its acceptance was strongly inhibited by fear, only partially justified, of severe side effects, but also, in the western world, by the difficulty to enter in combination with other vaccines: today multi-vaccine formulations are ...	2015	26051141
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
[vaccinations from the pulmonologist's point of view].	the best strategy for prevention of acute respiratory tract infections is primary prophylaxis against diseases preventable by vaccination. from the pulmonologist's point of view, vaccinations against pneumococci, influenza a and b viruses and bordetella pertussis are of particular clinical relevance.	2015	26059891
bordetella pertussis isolates circulating in china where whole cell vaccines have been used for 50 years.		2015	26060284
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
a field study of household attack rates and the effectiveness of macrolide antibiotics in reducing household transmission of pertussis.	bordetella pertussis (whooping cough) is an endemic, highly contagious bacterial respiratory infection, which is notifiable to australian state and territory health departments. between 2008 and 2011 there was a substantial outbreak in new south wales with an initial increase in cases occurring in north coast new south wales from late 2007. during september and october 2011 the north coast public health unit conducted a household study of secondary attack rates to assess the effectiveness of per ...	2015	26063095
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
bordetella holmesii infection: current knowledge and a vision for future research.	bordetella holmesii is a recently recognized gram-negative bacterium causing both pertussis-like respiratory symptoms and invasive infections, such as bacteremia, pneumonia, meningitis, arthritis, pericarditis and endocarditis. few data are available on its epidemiological characteristics, mostly related to respiratory infections. however, these are frequently misdiagnosed as a bordetella pertussis infection as most diagnostic tests routinely used are not species-specific, thus biasing the epide ...	2015	26065696
needle-free and adjuvant-free epicutaneous boosting of pertussis immunity: preclinical proof of concept.	the limited durability of pertussis vaccine-induced protection requires novel approaches to reactivate immunity and limit pertussis resurgence in older children and adults. we propose that periodic boosters could be delivered using a novel epicutaneous delivery system (viaskin) to deliver optimized pertussis antigens such as genetically-detoxified pertussis toxin (rpt). to best mimic the human situation in which vaccine-induced memory cells persist, whereas antibodies wane, we developed a novel ...	2015	26067183
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
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 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
association of targeted multiplex pcr with resequencing microarray for the detection of multiple respiratory pathogens.	a large number of viral and bacterial organisms are responsible for community-acquired pneumonia (cap) which contributes to substantial burden on health management. a new resequencing microarray (rpm-ivdc1) associated with targeted multiplex pcr was recently developed and validated for multiple respiratory viruses detection and discrimination. in this study, we evaluated the capability of rpm-ivdc1 for simultaneous identification of multiple viral and bacterial organisms. the nasopharyngeal aspi ...	2015	26074910