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structural characterization of humanized nanobodies with neutralizing activity against the bordetella pertussis cyaa-hemolysin: implications for a potential epitope of toxin-protective antigen.previously, the 126-kda cyaa-hemolysin (cyaa-hly) fragment cloned from bordetella pertussis--the causative agent of whooping cough--and functionally expressed in escherichia coli was revealed as a key determinant for cyaa-mediated hemolysis against target erythrocytes. here, phagemid-transfected e. coli clones producing nanobodies capable of binding to cyaa-hly were selected from a humanized-camel vh/vhh phage-display library. subsequently verified for binding activities by indirect elisa and we ...201627043627
quadracel: vaccination against diphtheria, tetanus, pertussis, and poliomyelitis in children.vaccinations in school-aged children are required by state and local law to maintain high vaccination coverage rates, as well as low rates of vaccine-preventable diseases. diphtheria, tetanus, and pertussis are childhood diseases that can be life threatening; poliomyelitis, another childhood disease, can be disabling. in turn, vaccinations were developed to provide protection against these diseases. today, several vaccinations are recommended for children, including but not limited to diphtheria ...201627069343
the camp pathway as therapeutic target in autoimmune and inflammatory diseases.nucleotide signaling molecules contribute to the regulation of cellular pathways. in the immune system, cyclic adenosine monophosphate (camp) is well established as a potent regulator of innate and adaptive immune cell functions. therapeutic strategies to interrupt or enhance camp generation or effects have immunoregulatory potential in autoimmune and inflammatory disorders. here, we provide an overview of the cyclic amp axis and its role as a regulator of immune functions and discuss the clinic ...201627065076
comparative genomic analysis reveals a diverse repertoire of genes involved in prokaryote-eukaryote interactions within the pseudovibrio genus.strains of the pseudovibrio genus have been detected worldwide, mainly as part of bacterial communities associated with marine invertebrates, particularly sponges. this recurrent association has been considered as an indication of a symbiotic relationship between these microbes and their host. until recently, the availability of only two genomes, belonging to closely related strains, has limited the knowledge on the genomic and physiological features of the genus to a single phylogenetic lineage ...201627065959
interaction of bacterial exotoxins with neutrophil extracellular traps: impact for the infected host.since their discovery in 2004, neutrophil extracellular traps (nets) have been characterized as a fundamental host innate immune defense against various pathogens. released in response to infectious and pro-inflammatory stimuli, nets can immobilize invading pathogens within a fibrous matrix consisting of dna, histones, and antimicrobial peptides. conversely, excessive or dysregulated net release may hold a variety of detrimental consequences for the host. a fine balance between net formation and ...201627064864
bacillus bombysepticus α-toxin binding to g protein-coupled receptor kinase 2 regulates camp/pka signaling pathway to induce host death.bacterial pathogens and their toxins target host receptors, leading to aberrant behavior or host death by changing signaling events through subversion of host intracellular camp level. this is an efficient and widespread mechanism of microbial pathogenesis. previous studies describe toxins that increase camp in host cells, resulting in death through g protein-coupled receptor (gpcr) signaling pathways by influencing adenylyl cyclase or g protein activity. g protein-coupled receptor kinase 2 (grk ...201627022742
community -and hospital laboratory-based surveillance for respiratory viruses.traditional surveillance for respiratory viruses relies on symptom detection and laboratory detection during medically attended encounters for acute respiratory infection/influenza-like illness (ari/ili). ecological momentary reporting using text messages is a novel method for surveillance. this study compares respiratory viral activity detected through longitudinal community-based surveillance using text message responses for sample acquisition and testing to respiratory viral activity obtained ...201626987664
vrah is the third component of the staphylococcus aureus vradeh system involved in gallidermin and daptomycin resistance and pathogenicity.in bacteria, extracellular signals are transduced into the cell predominantly by two-component systems (tcss) comprising a regulatory unit triggered by a specific signal. some of the tcss control executing units such as abc transporters involved in antibiotic resistance. for instance, instaphylococcus aureus, activation of brasr leads to the upregulation ofvradeexpression that encodes an abc transporter playing a role in bacitracin and nisin resistance. in this study, we show that the small stap ...201626856834
integrin-alpha iib identifies murine lymph node lymphatic endothelial cells responsive to rankl.microenvironment and activation signals likely imprint heterogeneity in the lymphatic endothelial cell (lec) population. particularly lecs of secondary lymphoid organs are exposed to different cell types and immune stimuli. however, our understanding of the nature of lec activation signals and their cell source within the secondary lymphoid organ in the steady state remains incomplete. here we show that integrin alpha 2b (itga2b), known to be carried by platelets, megakaryocytes and hematopoieti ...201627010197
the conformational signature of β-arrestin2 predicts its trafficking and signalling functions.arrestins are cytosolic proteins that regulate g-protein-coupled receptor (gpcr) desensitization, internalization, trafficking and signalling. arrestin recruitment uncouples gpcrs from heterotrimeric g proteins, and targets the proteins for internalization via clathrin-coated pits. arrestins also function as ligand-regulated scaffolds that recruit multiple non-g-protein effectors into gpcr-based 'signalsomes'. although the dominant function(s) of arrestins vary between receptors, the mechanism w ...201627007854
live and inactivated salmonella enterica serovar typhimurium stimulate similar but distinct transcriptome profiles in bovine macrophages and dendritic cells.salmonella enterica serovar typhimurium (s. typhimurium) is a major cause of gastroenteritis in cattle and humans. dendritic cells (dc) and macrophages (mø) are major players in early immunity to salmonella, and their response could influence the course of infection. therefore, the global transcriptional response of bovine monocyte-derived dc and mø to stimulation with live and inactivated s. typhimurium was compared. both cell types mount a major response 2 h post infection, with a core common ...201627000047
transcriptional analysis and subcellular protein localization reveal specific features of the essential walkr system in staphylococcus aureus.the walkr two-component system, controlling cell wall metabolism, is highly conserved among bacilli and essential for cell viability. in staphylococcus aureus, walr and walk are followed by three genes of unknown function: walh, wali and walj. sequence analysis and transcript mapping revealed a unique genetic structure for this locus in s. aureus: the last gene of the locus, walj, is transcribed independently, whereas transcription of the tetra-cistronic walrkhi operon occurred from two independ ...201626999783
restrained th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis.multiple sclerosis is a widespread inflammatory demyelinating disease. several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. accordingly, the search for new therapeutic methods constitutes an active investigation field. the use of mesenchymal stem cells (mscs) to modify the dis ...201626987803
sequestration of host metabolism by an intracellular pathogen.for intracellular pathogens, residence in a vacuole provides a shelter against cytosolic host defense to the cost of limited access to nutrients. the human pathogen chlamydia trachomatis grows in a glycogen-rich vacuole. how this large polymer accumulates there is unknown. we reveal that host glycogen stores shift to the vacuole through two pathways: bulk uptake from the cytoplasmic pool, and de novo synthesis. we provide evidence that bacterial glycogen metabolism enzymes are secreted into the ...201626981769
targeting staphylococcus aureus toxins: a potential form of anti-virulence therapy.staphylococcus aureus is an opportunistic pathogen and the leading cause of a wide range of severe clinical infections. the range of diseases reflects the diversity of virulence factors produced by this pathogen. to establish an infection in the host, s. aureus expresses an inclusive set of virulence factors such as toxins, enzymes, adhesins, and other surface proteins that allow the pathogen to survive under extreme conditions and are essential for the bacteria's ability to spread through tissu ...201626999200
effect of infant formula containing a low dose of the probiotic bifidobacterium lactis cncm i-3446 on immune and gut functions in c-section delivered babies: a pilot study.in the absence of breast-feeding and its immunomodulatory factors, supplementation of starter infant formula (if) with probiotics is currently used to support immune functions and gut development.201626997881
viruses as sole causative agents of severe acute respiratory tract infections in children.respiratory syncytial virus (rsv) and influenza a viruses are known to cause severe acute respiratory tract infections (saris) in children. for other viruses like human rhinoviruses (hrvs) this is less well established. viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections.201626964038
cns accumulation of regulatory b cells is vla-4-dependent.to investigate the role of very late antigen-4 (vla-4) on regulatory b cells (breg) in cns autoimmune disease.201627027096
effectiveness of n95 respirators versus surgical masks in protecting health care workers from acute respiratory infection: a systematic review and meta-analysis.conflicting recommendations exist related to which facial protection should be used by health care workers to prevent transmission of acute respiratory infections, including pandemic influenza. we performed a systematic review of both clinical and surrogate exposure data comparing n95 respirators and surgical masks for the prevention of transmissible acute respiratory infections.201626952529
changes in predominance of pulsed-field gel electrophoresis profiles of bordetella pertussis isolates, united states, 2000-2012.to clarify the characteristics of circulating bordetella pertussis isolates, we used pulsed-field gel electrophoresis (pfge) to analyze 5,262 isolates collected in the united states during 2000-2012. we found 199 pfge profiles; 5 profiles accounted for 72% of isolates. the most common profile, cdc013, accounted for 35%-46% of isolates tested from 2000-2009; however, the proportion of isolates of this profile rapidly decreased in 2010. profile cdc237, first seen in 2009, increased rapidly and acc ...201626886905
regulation of th2 cell immunity by dendritic cells.th2 cell immunity is required for host defense against helminths, but it is detrimental in allergic diseases in humans. unlike th1 cell and th17 cell subsets, the mechanism by which dendritic cells modulate th2 cell responses has been obscure, in part because of the inability of dendritic cells to provide il-4, which is indispensable for th2 cell lineage commitment. in this regard, immune cells other than dendritic cells, such as basophils and innate lymphoid cells, have been suggested as th2 ce ...201626937227
potential molecular targets for narrow-spectrum agents to combat mycoplasma pneumoniae infection and disease.as mycoplasma pneumoniae macrolide resistance grows and spreads worldwide, it is becoming more important to develop new drugs to prevent infection or limit disease. because other mycoplasma species have acquired resistance to other classes of antibiotics, it is reasonable to presume that m. pneumoniae can do the same, so switching to commonly used antibiotics like fluoroquinolones will not result in forms of therapy with long-term utility. moreover, broad-spectrum antibiotics can have serious co ...201626941728
characterization of new virulence factors involved in the intracellular growth and survival of burkholderia pseudomallei.burkholderia pseudomallei, the causative agent of melioidosis, has complex and poorly understood extracellular and intracellular lifestyles. we used transposon-directed insertion site sequencing (tradis) to retrospectively analyze a transposon library that had previously been screened through a balb/c mouse model to identify genes important for growth and survival in vivo. this allowed us to identify the insertion sites and phenotypes of negatively selected mutants that were previously overlooke ...201626712202
comparing seasonal pattern of laboratory confirmed cases of pertussis with clinically suspected cases.during recent decades, there has been limited attention on the seasonal pattern of pertussis within a high vaccine coverage population. this study aimed to compare the seasonal patterns of clinical suspected pertussis cases with those of laboratory confirmed cases in iran.201627169013
imbalance of th17/tregs in rats with smoke inhalation-induced acute lung injury.t helper (th) 17 cells and cd4(+) cd25(+) regulatory t (treg) cells are supposed to be critically involved in regulating autoimmune and inflammatory diseases. the aim of this study was to investigate the th17/treg pattern in rats with gunpowder smog-induced acute lung injury. wistar rats were equally randomized to three groups: normal control group, ali 6 h group (smoke inhalation for 6 h) and ali 24 h group (smoke inhalation for 24 h). we observed changes in cell counting in bronchoalveolar lav ...201626884314
pendrin, an anion exchanger on lung epithelial cells, could be a novel target for lipopolysaccharide-induced acute lung injury mice.the aim of this study is to evaluate the role of pendrin in acute lung injury (ali)/acute respiratory distress syndrome (ards) and to explore whether pendrin expression existing on alveolar cells.201627158384
disulfide-bond-forming pathways in gram-positive bacteria.disulfide bonds are important for the stability and function of many secreted proteins. in gram-negative bacteria, these linkages are catalyzed by thiol-disulfide oxidoreductases (dsb) in the periplasm. protein oxidation has been well studied in these organisms, but it has not fully been explored in gram-positive bacteria, which lack traditional periplasmic compartments. recent bioinformatics analyses have suggested that the high-gc-content bacteria (i.e., actinobacteria) rely on disulfide-bond- ...201626644434
expression of caga, virb/d complex and/or vaca genes in helicobacter pylori strains originating from patients with gastric diseases.in order to better understand pathogenicity of helicobacter pylori, particularly in the context of its carcinogenic activity, we analysed expression of virulence genes: caga, virb/d complex (virb4, virb7, virb8, virb9, virb10, virb11, vird4) and vaca in strains of the pathogen originating from persons with gastric diseases. the studies were conducted on 42 strains of h. pylori isolated from patients with histological diagnosis of non-atrophic gastritis-nag (group 1, including subgroup 1 containi ...201626866365
histophilus somni stimulates expression of antiviral proteins and inhibits brsv replication in bovine respiratory epithelial cells.our previous studies showed that bovine respiratory syncytial virus (brsv) followed by histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. however, microarray analysis revealed the treatment of bovine alveolar type 2 (bat2) epithelial cells with h. somni concentrated culture supernatant (ccs) stimulated up-regulation of four antiviral protein genes as compared with brsv infection or dual treatment. this suggested ...201626859677
il-1-induced bhlhe40 identifies pathogenic t helper cells in a model of autoimmune neuroinflammation.the features that define autoreactive t helper (th) cell pathogenicity remain obscure. we have previously shown that th cells require the transcription factor bhlhe40 to mediate experimental autoimmune encephalomyelitis (eae), a mouse model of multiple sclerosis. here, using bhlhe40 reporter mice and analyzing both polyclonal and tcr transgenic th cells, we found that bhlhe40 expression was heterogeneous after eae induction, with bhlhe40-expressing cells displaying marked production of ifn-γ, il ...201626834156
multi-tissue transcriptomics for construction of a comprehensive gene resource for the terrestrial snail theba pisana.the land snail theba pisana is native to the mediterranean region but has become one of the most abundant invasive species worldwide. here, we present three transcriptomes of this agriculture pest derived from three tissues: the central nervous system, hepatopancreas (digestive gland), and foot muscle. sequencing of the three tissues produced 339,479,092 high quality reads and a global de novo assembly generated a total of 250,848 unique transcripts (unigenes). blast analysis mapped 52,590 unige ...201626852673
childhood febrile illness and the risk of myopia in uk biobank participants.historical reports suggest febrile illness during childhood is a risk factor for myopia. the establishment of the uk biobank provided a unique opportunity to investigate this relationship.201626846593
involvement of b cells in non-infectious uveitis.non-infectious uveitis-or intraocular inflammatory disease-causes substantial visual morbidity and reduced quality of life amongst affected individuals. to date, research of pathogenic mechanisms has largely been focused on processes involving t lymphocyte and/or myeloid leukocyte populations. involvement of b lymphocytes has received relatively little attention. in contrast, b-cell pathobiology is a major field within general immunological research, and large clinical trials have showed that tr ...201626962453
the use of innovative two-component cluster analysis and serodiagnostic cut-off methods to estimate prevalence of pertussis reinfections.bordetella pertussis circulates even in highly vaccinated countries affecting all age groups. insight into the scale of concealed reinfections is important as they may contribute to transmission. we therefore investigated whether current single-point serodiagnostic methods are suitable to estimate the prevalence of pertussis reinfection. two methods based on igg-ptx plasma levels alone were used to evaluate the proportion of renewed seroconversions in the past year in a cohort of retrospective p ...201626848833
current therapeutic vaccination and immunotherapy strategies for hpv-related diseases.carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. human papillomavirus (hpv)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. the causal relationship between hpv infection and anogenital cancer has prompted substantial i ...201626835746
seroprevalence of antibodies to pertussis toxin among different age groups in thailand after 37 years of universal whole-cell pertussis vaccination.despite the high coverage of prophylactic vaccine against bordetella pertussis infection in many countries for more than three decades, pertussis remains a common vaccine-preventable disease. infections have been detected more commonly in countries using acellular pertussis vaccine in their expanded program of immunization. thailand implemented a routine infant immunization program with whole-cell pertussis vaccine in 1977, and since 1992, the national vaccine policy has offered a five-dose whol ...201626837004
targeting autophagy to sensitive glioma to temozolomide treatment.temozolomide (tmz), an alkylating agent, is widely used for treating primary and recurrent high-grade gliomas. however, the efficacy of tmz is often limited by the development of resistance. recently, studies have found that tmz treatment could induce autophagy, which contributes to therapy resistance in glioma. to enhance the benefit of tmz in the treatment of glioblastomas, effective combination strategies are needed to sensitize glioblastoma cells to tmz. in this regard, as autophagy could pr ...201626830677
iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies.iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (cf) lung. the multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and species-specific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. pathoge ...201626643057
loss of function of intestinal il-17 and il-22 producing cells contributes to inflammation and viral persistence in siv-infected rhesus macaques.in hiv/siv-infected humans and rhesus macaques (rms), a severe depletion of intestinal cd4(+) t-cells producing interleukin il-17 and il-22 associates with loss of mucosal integrity and chronic immune activation. however, little is known about the function of il-17 and il-22 producing cells during lentiviral infections. here, we longitudinally determined the levels and functions of il-17, il-22 and il-17/il-22 producing cd4(+) t-cells in blood, lymph node and colorectum of siv-infected rms, as w ...201626829644
validation of cis and trans modes in multistep phosphotransfer signaling of bacterial tripartite sensor kinases by using phos-tag sds-page.tripartite sensor kinases (tsks) have three phosphorylation sites on his, asp, and his residues, which are conserved in a histidine kinase (hk) domain, a receiver domain, and a histidine-containing phosphotransmitter (hpt) domain, respectively. by means of a three-step phosphorelay, tsks convey a phosphoryl group from the γ-phosphate group of atp to the first his residue in the hk domain, then to the asp residue in the receiver domain, and finally to the second his residue in the hpt domain. alt ...201626828204
bordetella pertussis strain lacking pertactin and pertussis toxin.a bordetella pertussis strain lacking 2 acellular vaccine immunogens, pertussis toxin and pertactin, was isolated from an unvaccinated infant in new york state in 2013. comparison with a french strain that was pertussis toxin-deficient, pertactin wild-type showed that the strains carry the same 28-kb deletion in similar genomes.201626812174
sustained transmission of pertussis in vaccinated, 1-5-year-old children in a preschool, florida, usa. 201626814429
bacterial toxins as pathogen weapons against phagocytes.bacterial toxins are virulence factors that manipulate host cell functions and take over the control of vital processes of living organisms to favor microbial infection. some toxins directly target innate immune cells, thereby annihilating a major branch of the host immune response. in this review we will focus on bacterial toxins that act from the extracellular milieu and hinder the function of macrophages and neutrophils. in particular, we will concentrate on toxins from gram-positive and gram ...201626870008
mit1 transcription factor mediates methanol signaling and regulates the alcohol oxidase 1 (aox1) promoter in pichia pastoris.the alcohol oxidase 1 (aox1) promoter (p aox1) of pichia pastoris is the most powerful and commonly used promoter for driving protein expression. however, mechanisms regulating its transcriptional activity are unclear. here, we identified a zn(ii)2cys6-type methanol-induced transcription factor 1 (mit1) and elucidated its roles in regulating paox1 activity in response to glycerol and methanol. mit1 regulated the expression of many genes involved in methanol utilization pathway, including aox1, b ...201626828066
chao yuanfang: imperial physician of the sui dynasty and an early pertussis observer?early chinese texts contain extensive disease descriptions, including various texts that contain descriptions of modern-day conditions. during the sui dynasty, a leading scholar, chao yuanfang, may have authored a leading treatise 1400 years ago. although these texts are the subject of ongoing research, evidence suggests that a clinical syndrome consistent with pertussis was observed in ancient china.201626977422
efforts to improve immunization coverage during pregnancy among ob-gyns.influenza and tdap vaccines are vital factors for improving maternal and neonatal health outcomes.201626924918
deciphering parameter sensitivity in the bvgas signal transduction.to understand the switching of different phenotypic phases of bordetella pertussis, we propose an optimized mathematical framework for signal transduction through bvgas two-component system. the response of the network output to the sensory input has been demonstrated in steady state. an analysis in terms of local sensitivity amplification characterizes the nature of the molecular switch. the sensitivity analysis of the model parameters within the framework of various correlation coefficients he ...201626812153
nonredundant roles of iron acquisition systems in vibrio cholerae.vibrio cholerae, the causative agent of the severe diarrheal disease cholera, thrives in both marine environments and the human host. to do so, it must encode the tools necessary to acquire essential nutrients, including iron, under these vastly different conditions. a number of v. cholerae iron acquisition systems have been identified; however, the precise role of each system is not fully understood. to test the roles of individual systems, we generated a series of mutants in which only one of ...201626644383
lung infection by human bocavirus induces the release of profibrotic mediator cytokines in vivo and in vitro.human bocavirus subtype 1 (hbov1) is associated with respiratory diseases and may contribute to chronic lung diseases by persisting in the infected host. here the question was addressed if hbov infections could contribute to fibrogenesis processes as suggested by previously published clinical observations. cytokine profiles induced by hbov infection in cufi-8 air-liquid interphase cell cultures and in bronchoalveolar lavage fluid (balf) of 20 hbov-positive and 12 hbov-negative patients were anal ...201626807786
vaccines directed against microorganisms or their products present during biofilm lifestyle: can we make a translation as a broad biological model to tuberculosis?tuberculosis (tb) remains as a global public health problem. in recent years, experimental evidence suggesting the relevance of in vitro pellicle (a type of biofilm formed at the air-liquid interface) production as a phenotype mimicking aspects found by mycobacterium tuberculosis-complex bacteria during in vivo infection has started to accumulate. there are still opportunities for better diagnostic tools, therapeutic molecules as well as new vaccine candidates to assist in tb control programs wo ...201626834732
detection of clostridium perfringens alpha toxin gene in lambs by loop mediated isothermal amplification.the loop mediated isothermal amplification (lamp) was standardized for rapid detection of clostridium perfringens.201627051186
maternal immunization earlier in pregnancy maximizes antibody transfer and expected infant seropositivity against pertussis.maternal immunization against pertussis is currently recommended after the 26th gestational week (gw). data on the optimal timing of maternal immunization are inconsistent.201626797213
overexpression of rorγt enhances pulmonary inflammation after infection with mycobacterium avium.mycobacterium avium complex (mac) is the most common cause of nontuberculous mycobacterial disease in humans. the role of th17 immunity in the pathogenesis of intracellular bacteria, such as mac, is not currently understood. transcription factor rar-related orphan receptor gamma t (rorγt) is known as the master regulator for th17 cell development. here, we investigated the role of rorγt in host responses against mac infection. wild-type (wt) mice and rorγt-overexpressing mice were infected with ...201626784959
phenotypes associated with the essential diadenylate cyclase cdaa and its potential regulator cdar in the human pathogen listeria monocytogenes.cyclic diadenylate monophosphate (c-di-amp) is a second messenger utilized by diverse bacteria. in many species, including the gram-positive human pathogen listeria monocytogenes, c-di-amp is essential for growth. here we show that the single diadenylate cyclase of l. monocytogenes, cdaa, is an integral membrane protein that interacts with its potential regulatory protein, cdar, via the transmembrane protein domain. the presence of the cdar protein is not required for the membrane localization a ...201626527648
helicobacter pylori infection and gastric carcinoma: not all the strains and patients are alike.gastric carcinoma (gc) develops in only 1%-3% of helicobacter pylori (h. pylori) infected people. the role in gc formation of the bacterial genotypes, gene polymorphisms and host's factors may therefore be important. the risk of gc is enhanced when individuals are infected by strains expressing the oncoprotein caga, in particular if caga has a high number of repeats containing the epiya sequence in its c'-terminal variable region or particular amino acid sequences flank the epiya motifs. h. pylo ...201626798436
the pertussis enigma: reconciling epidemiology, immunology and evolution.pertussis, a highly contagious respiratory infection, remains a public health priority despite the availability of vaccines for 70 years. still a leading cause of mortality in developing countries, pertussis has re-emerged in several developed countries with high vaccination coverage. resurgence of pertussis in these countries has routinely been attributed to increased awareness of the disease, imperfect vaccinal protection or high infection rates in adults. in this review, we first present 1980 ...201626763701
the resurgence of mumps and pertussis.vaccines and extended vaccination programs have had an extensive impact on morbidity and mortality rates due to infectious diseases. because of the continuous and extensive use of vaccines in industrialized countries, many infectious diseases such as poliomyelitis, diphtheria and measles have been reduced to near-extinction. however, in recent years, many countries including the united states of america, the united kingdom and belgium, have been confronted with a resurgence of mumps and pertussi ...201626751186
use of a probabilistic motif search to identify histidine phosphotransfer domain-containing proteins.the wealth of newly obtained proteomic information affords researchers the possibility of searching for proteins of a given structure or function. here we describe a general method for the detection of a protein domain of interest in any species for which a complete proteome exists. in particular, we apply this approach to identify histidine phosphotransfer (hpt) domain-containing proteins across a range of eukaryotic species. from the sequences of known hpt domains, we created an amino acid occ ...201626751210
quantitation of polymyxin-lipopolysaccharide interactions using an image-based fluorescent probe.the frequency of polymyxin-resistant pathogenic gram-negative bacteria appearing in the clinic is increasing, and the consequences are largely mediated by modification of lipopolysaccharide (lps) in the outer membrane. as polymyxins exert their antibacterial effect by binding to lps, understanding their mode of binding will prove highly valuable for new antibiotic discovery. in this study, we assess the potential of mips-9451, a fluorescent polymyxin analogue designed for imaging studies, as a f ...201626869441
comparison of three whole-cell pertussis vaccines in the baboon model of pertussis.pertussis is a highly contagious respiratory illness caused by the bacterial pathogen bordetella pertussis. pertussis rates in the united states have escalated since the 1990s and reached a 50-year high of 48,000 cases in 2012. while this pertussis resurgence is not completely understood, we previously showed that the current acellular pertussis vaccines do not prevent colonization or transmission following challenge. in contrast, a whole-cell pertussis vaccine accelerated the rate of clearance ...201626561389
cxcl14 as an emerging immune and inflammatory modulator.cxcl14, a relatively novel chemokine, is a non-elr (glutamic acid-leucine-arginine) chemokine with a broad spectrum of biological activities. cxcl14 mainly contributes to the regulation of immune cell migration, also executes antimicrobial immunity. the identity of the receptor for cxcl14 still remains obscure and therefore the intracellular signaling pathway is not entirely delineated. the present review summarizes the contribution of cxcl14 in these two aspects and discusses the biological mec ...201626733763
alternatives to hist for acellular pertussis vaccines: progress and challenges in replacement.the 'international workshop on alternatives to the murine histamine sensitization test for acellular pertussis vaccines: progress and challenges in the replacement of hist' was held on 24 august 2014, in prague, czech republic, as a satellite meeting to the 9th world congress on alternatives and animal use in the life sciences. participants discussed the progress and challenges associated with the development, validation, and implementation of in vitro assays as replacements for the histamine se ...201627506225
acute ischemic optic neuropathy with extended prone position ventilation in a lung transplant recipient.prone position ventilation (ppv) improves mortality in severe acute respiratory distress syndrome (ards), but outcomes following its use in lung transplant recipients are not known. we report the case of a 42-year-old caucasian man who presented with severe ards from bordetella pertussis, 5 years after bilateral sequential lung transplant for cystic fibrosis. he was managed with ppv for 22 days and had a prolonged icu stay complicated by hypoxic ischemic optic neuropathy leading to blindness. si ...201627051622
interdicting gq activation in airway disease by receptor-dependent and receptor-independent mechanisms.gαqβγ heterotrimer (gq), an important mediator in the pathology of airway disease, plays a central role in bronchoconstriction and airway remodeling, including airway smooth muscle growth and inflammation. current therapeutic strategies to treat airway disease include the use of muscarinic and leukotriene receptor antagonists; however, these pharmaceuticals demonstrate a limited clinical efficacy as multiple gq-coupled receptor subtypes contribute to these pathologies. thus, broadly inhibiting t ...201626464325
legionnaires' disease in south africa, 2012-2014.during june 2012-september 2014, we tested patients with severe respiratory illness for legionella spp. infection and conducted a retrospective epidemiologic investigation. of 1,805 patients tested, legionella was detected in samples of 21 (1.2%); most were adults who had hiv or tuberculosis infections and were inappropriately treated for legionella.201626692504
immunogenicity in dogs and protection against visceral leishmaniasis induced by a 14kda leishmania infantum recombinant polypeptide.in areas were human visceral leishmaniasis (vl) is endemic, the domestic dog is the main parasite reservoir in the infectious cycle of leishmania infantum. development of prophylactic strategies to lower the parasite burden in dogs would reduce sand fly transmission thus lowering the incidence of zoonotic vl. here we demonstrate that vaccination of dogs with a recombinant 14kda polypeptide of l. infantum nuclear transport factor 2 (li-ntf2) mixed with adjuvant bpmpla-se resulted in the productio ...201626640609
morbidity and mortality due to bordetella pertussis: a significant pathogen in west africa?in the absence of specific surveillance platforms for pertussis and availability of suitable diagnostics at the hospital level, reliable data that describe morbidity and mortality from pertussis are difficult to obtain in any setting, as is the case in west africa. here, we summarize the available evidence of the burden of pertussis in the region, given historical data, and describe recent and ongoing epidemiological studies that offer opportunities for additional data collection. the available ...201627838666
incidence of severe and nonsevere pertussis among hiv-exposed and -unexposed zambian infants through 14 weeks of age: results from the southern africa mother infant pertussis study (samips), a longitudinal birth cohort study.maternal vaccination with tetanus, reduced-dose diphtheria, and acellular pertussis vaccine (tdap) could be an effective way of mitigating the high residual burden of infant morbidity and mortality caused by bordetella pertussis to better inform such interventions, we conducted a burden-of-disease study to determine the incidence of severe and nonsevere pertussis among a population of zambian infants.201627838668
epidemiology and economic burden of measles, mumps, pertussis, and varicella in germany: a systematic review.despite the availability of vaccines and the existence of public vaccination recommendations, outbreaks of vaccine-preventable childhood diseases still cause public health debate. the objective of this systematic review was to provide an overview of the current epidemiology and economic burden of measles, mumps, pertussis, and varicella in germany.201627488917
old disease and new challenges: major obstacles of current strategies in the prevention of pertussis.universal immunization against bordetella pertussis has partially controlled the burden of the disease and its transmission. however, according to recent data, the epidemiology of this vaccine-preventable disease has changed. now, younger infants, adolescents, and adults are at greater risk of infection. this article has studied the interaction between the various factors involved in the changing epidemiology of pertussis and the major obstacles faced by the current strategies in its prevention.201627729960
comparison of molecular detection methods for pertussis in children during a state-wide outbreak.a state-wide pertussis outbreak occurred in washington during the winter-spring months of 2012, concurrent with respiratory viral season. we compared performance characteristics of a laboratory-developed pertussis pcr (ld-pcr for bordetella pertussis, bordetella parapertussis, and bordetella holmesii) and rapid multiplex pcr (rm-pcr) for respiratory viruses (filmarray™, biofire, b. pertussis data unblinded following fda approval post outbreak). we analyzed three cohorts of patients using physici ...201627121506
comparing the yield of nasopharyngeal swabs, nasal aspirates, and induced sputum for detection of bordetella pertussis in hospitalized infants.advances in molecular laboratory techniques are changing the landscape of bordetella pertussis illness diagnosis. polymerase chain reaction (pcr) assays have greatly improved the sensitivity detection and the turnaround time to diagnosis compared to culture. moreover, different respiratory specimens, such as flocked nasopharyngeal swabs (npss), nasopharyngeal aspirates (npas), and induced sputum, have been used for b. pertussis detection, although there is limited head-to-head comparison to eval ...201627838671
pertussis-like syndrome associated with adenovirus presenting with hyperleukocytosis: case report.adenovirus is an infectious viral agent that causes variety of clinical presentations such as respiratory disease, conjunctivitis, and gastroenteritis. hepatitis, pancreatitis, myocarditis, encephalitis, and disseminated infection are primarily seen in immunocompromised patients. rarely, adenovirus infection can present with pertussis-like syndrome. described here is case of pertussis-like syndrome associated with adenovirus presenting with hyperleukocytosis.201628058402
the multifaceted risa regulon of bordetella pertussis.the whooping cough agent bordetella pertussis regulates the production of its virulence factors by the bvga/s system. phosphorylated bvga activates the virulence-activated genes (vags) and represses the expression of the virulence-repressed genes (vrgs) via the activation of the bvgr gene. in modulating conditions, with mgso4, the bvga/s system is inactive, and the vrgs are expressed. here, we show that the expression of almost all vrgs depends on risa, another transcriptional regulator. we also ...201627620673
bipa is associated with preventing autoagglutination and promoting biofilm formation in bordetella holmesii.bordetella holmesii causes both invasive and respiratory diseases in humans. although the number of cases of pertussis-like respiratory illnesses due to b. holmesii infection has increased in the last decade worldwide, little is known about the virulence factors of the organism. here, we analyzed a b. holmesii isolate that forms large aggregates and precipitates in suspension, and subsequently demonstrated that the autoagglutinating isolate is deficient in bordetella intermediate protein a (bipa ...201627448237
bordetella pertussis: new concepts in pathogenesis and treatment.the purpose of this review is to summarize and discuss recent findings and selected topics of interest in bordetella pertussis virulence and pathogenesis and treatment of pertussis. it is not intended to cover issues on immune responses to b. pertussis infection or problems with currently used pertussis vaccines.201626906206
differential regulation of type iii secretion and virulence genes in bordetella pertussis and bordetella bronchiseptica by a secreted anti-σ factor.the bvgas phosphorelay regulates ∼10% of the annotated genomes of bordetella pertussis and bordetella bronchiseptica and controls their infectious cycles. the hierarchical organization of the regulatory network allows the integration of contextual signals to control all or specific subsets of bvgas-regulated genes. here, we characterize a regulatory node involving a type iii secretion system (t3ss)-exported protein, btra, and demonstrate its role in determining fundamental differences in t3ss ph ...201626884180
btea secreted from the bordetella bronchiseptica type iii secetion system induces necrosis through an actin cytoskeleton signaling pathway and inhibits phagocytosis by macrophages.btea is one of the effectors secreted from the bordetella bronchiseptica type iii secretion system. it has been reported that btea induces necrosis in mammalian cells; however, the roles of btea during the infection process are largely unknown. in order to investigate the btea functions, morphological changes of the cells infected with the wild-type b. bronchiseptica were examined by time-lapse microscopy. l2 cells, a rat lung epithelial cell line, spread at 1.6 hours after b. bronchiseptica inf ...201626828590
assessing sex-differences and the effect of timing of vaccination on immunogenicity, reactogenicity and efficacy of vaccines in young children: study protocol for an individual participant data meta-analysis of randomised controlled trials.disease incidence differs between males and females for some infectious or inflammatory diseases. sex-differences in immune responses to some vaccines have also been observed, mostly to viral vaccines in adults. little evidence is available on whether sex-differences occur in response to immunisation in infancy even though this is the age group in which most vaccines are administered. factors other than sex, such as timing or coadministration of other vaccines, can also influence the immune resp ...201627473951
a systematic review of ethical issues in vaccine studies involving pregnant women.immunization during pregnancy can provide protection for mother and child. however, there have been only a limited number of studies documenting the efficacy and safety of this strategy.201627246403
transcriptome signature for dampened th2 dominance in acellular pertussis vaccine-induced cd4(+) t cell responses through tlr4 ligation.current acellular pertussis (ap) vaccines promote a t helper 2 (th2)-dominated response, while th1/th17 cells are protective. as our previous study showed, after adding a non-toxic tlr4 ligand, lpxl1, to the ap vaccine in mice, the bordetella pertussis-specific th2 response is decreased and th1/th17 responses are increased as measured at the cytokine protein level. however, how this shift in th response by lpxl1 addition is regulated at the gene expression level remains unclear. transcriptomics ...201627118638
diagnosis of bacterial bloodstream infections: a 16s metagenomics approach.bacterial bloodstream infection (bbsi) is one of the leading causes of death in critically ill patients and accurate diagnosis is therefore crucial. we here report a 16s metagenomics approach for diagnosing and understanding bbsi.201626927306
genome stability of propionibacterium acnes: a comprehensive study of indels and homopolymeric tracts.we present a species-wide comparative analysis of 90 genomes of propionibacterium acnes that represent the known diversity of the species. our results are augmented by six high-quality genomes and a manual investigation of all gene-sized indels found in the strains. overall, the order of genes is conserved throughout the species. a public sybil database for easy comparative analysis of the 90 genomes was established. the analysis of indels revealed a total of 66 loci of non-core genes that corre ...201626857276
vaccine-preventable infections in systemic lupus erythematosus.systemic lupus erythematosus (sle) is characterized by abnormal autoantibody production and clearance. infections are among the most important causes of morbidity and mortality in sle patients; they have an increased frequency of severe bacterial and viral infections possibly due to inherited genetic and immunologic defects and to immunosuppressive therapies. in addition, infectious agents can switch on lupus disease expression and activity. among the strategies to reduce the risk of infection, ...201626750996
respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in cape town, south africa.lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. children with symptoms suggestive of pulmonary tuberculosis (ptb) may have tuberculosis, other respiratory tract infections or co-infection with mycobacterium tuberculosis and other pathogens. we aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (np) samples from children with suspected ptb.201627776489
neuroendocrine cell hyperplasia of infancy: an unusual cause of hypoxemia in children.childhood interstitial lung disease (child) is a heterogeneous group of rare disorders characterized by abnormal imaging findings, impaired gas exchange; and is associated with substantial morbidity and mortality. neuroendocrine cell hyperplasia (nehi) is a unique sub-group, which is more prevalent in infants and children younger than 2 years of age, and typically manifests with chronic tachypnea, retractions, hypoxemia and failure to thrive. nehi insidiously appears in the first year of life, s ...201627629751
provider decisions to treat respiratory illnesses with antibiotics: insights from a randomized controlled trial.lower respiratory tract illness (lrti) frequently causes adult hospitalization and antibiotic overuse. procalcitonin (pct) treatment algorithms have been used successfully in europe to safely reduce antibiotic use for lrti but have not been adopted in the united states. we recently performed a feasibility study for a randomized clinical trial (rct) of pct and viral testing to guide therapy for non-pneumonic lrti.201627043012
identification of bacterial and viral codetections with mycoplasma pneumoniae using the taqman array card in patients hospitalized with community-acquired pneumonia.mycoplasma pneumoniae was detected in a number of patients with community-acquired pneumonia in a recent prospective study. to assess whether other pathogens were also detected in these patients, taqman array cards were used to test 216 m pneumoniae-positive respiratory specimens for 25 additional viral and bacterial respiratory pathogens. it is interesting to note that 1 or more codetections, predominantly bacterial, were identified in approximately 60% of specimens, with codetections being mor ...201627191004
depletion of human dna in spiked clinical specimens for improvement of sensitivity of pathogen detection by next-generation sequencing.next-generation sequencing (ngs) technology has shown promise for the detection of human pathogens from clinical samples. however, one of the major obstacles to the use of ngs in diagnostic microbiology is the low ratio of pathogen dna to human dna in most clinical specimens. in this study, we aimed to develop a specimen-processing protocol to remove human dna and enrich specimens for bacterial and viral dna for shotgun metagenomic sequencing. cerebrospinal fluid (csf) and nasopharyngeal aspirat ...201626763966
the role of respiratory viruses in the etiology of bacterial pneumonia: an ecological perspective.pneumonia is the leading cause of death among children less than 5 years old worldwide. a wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. seconda ...201626884414
a novel mechanism for the biogenesis of outer membrane vesicles in gram-negative bacteria.bacterial outer membrane vesicles (omvs) have important biological roles in pathogenesis and intercellular interactions, but a general mechanism of omv formation is lacking. here we show that the vacj/yrb abc (atp-binding cassette) transport system, a proposed phospholipid transporter, is involved in omv formation. deletion or repression of vacj/yrb increases omv production in two distantly related gram-negative bacteria, haemophilus influenzae and vibrio cholerae. lipidome analyses demonstrate ...201626806181
neisserial heparin binding antigen (nhba) contributes to the adhesion of neisseria meningitidis to human epithelial cells.neisserial heparin binding antigen (nhba) is a surface-exposed lipoprotein ubiquitously expressed by neisseria meningitidis strains and an antigen of the bexsero® vaccine. nhba binds heparin through a conserved arg-rich region that is the target of two proteases, the meningococcal nalp and human lactoferrin (hlf). in this work, in vitro studies showed that recombinant nhba protein was able to bind epithelial cells and mutations of the arg-rich tract abrogated this binding. all n-terminal and c-t ...201627780200
how can vaccines contribute to solving the antimicrobial resistance problem?there is a growing appreciation for the role of vaccines in confronting the problem of antimicrobial resistance (amr). vaccines can reduce the prevalence of resistance by reducing the need for antimicrobial use and can reduce its impact by reducing the total number of cases. by reducing the number of pathogens that may be responsible for a particular clinical syndrome, vaccines can permit the use of narrower-spectrum antibiotics for empirical therapy. these effects may be amplified by herd immun ...201627273824
polyethersulfone improves isothermal nucleic acid amplification compared to current paper-based diagnostics.devices based on rapid, paper-based, isothermal nucleic acid amplification techniques have recently emerged with the potential to fill a growing need for highly sensitive point-of-care diagnostics throughout the world. as this field develops, such devices will require optimized materials that promote amplification and sample preparation. herein, we systematically investigated isothermal nucleic acid amplification in materials currently used in rapid diagnostics (cellulose paper, glass fiber, and ...201626906904
different use of cell surface glycosaminoglycans as adherence receptors to corneal cells by gram positive and gram negative pathogens.the epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. in this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. all microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the gram-type of the bacterium. the heparan sulfate chains of syndecans are the main re ...201627965938
multifunctional and redundant roles of borrelia burgdorferi outer surface proteins in tissue adhesion, colonization, and complement evasion.borrelia burgdorferi is the causative agent of lyme disease in the u.s., with at least 25,000 cases reported to the cdc each year. b. burgdorferi is thought to enter and exit the bloodstream to achieve rapid dissemination to distal tissue sites during infection. travel through the bloodstream requires evasion of immune surveillance and pathogen clearance in the host, a process at which b. burgdorferi is adept. b. burgdorferi encodes greater than 19 adhesive outer surface proteins many of which h ...201627818662
immunoglobulin m for acute infection: true or false?immunoglobulin m (igm) tests have clear clinical utility but also suffer disproportionately from false-positive results, which in turn can lead to misdiagnoses, inappropriate therapy, and premature closure of a diagnostic workup. despite numerous reports in the literature, many clinicians and laboratorians remain unaware of this issue. in this brief review, a series of virology case examples is presented. however, a false-positive igm can occur with any pathogen. thus, when an accurate diagnosis ...201627193039
pilz domain protein flgz mediates cyclic di-gmp-dependent swarming motility control in pseudomonas aeruginosa.the second messenger cyclic diguanylate (c-di-gmp) is an important regulator of motility in many bacterial species. in pseudomonas aeruginosa, elevated levels of c-di-gmp promote biofilm formation and repress flagellum-driven swarming motility. the rotation of p. aeruginosa's polar flagellum is controlled by two distinct stator complexes, motab, which cannot support swarming motility, and motcd, which promotes swarming motility. here we show that when c-di-gmp levels are elevated, swarming motil ...201627114465
understanding neuropsychiatric diseases, analyzing the peptide sharing between infectious agents and the language-associated nmda 2a protein.language disorders and infections may occur together and often concur, to a different extent and via different modalities, in characterizing brain pathologies, such as schizophrenia, autism, epilepsies, bipolar disorders, frontotemporal neurodegeneration, and encephalitis, inter alia. the biological mechanism(s) that might channel language dysfunctions and infections into etiological pathways connected to neuropathologic sequelae are unclear. searching for molecular link(s) between language diso ...201627148089
point-counterpoint: the fda has a role in regulation of laboratory-developed tests.since the food and drug administration (fda) released its draft guidance on the regulation of laboratory-developed tests (ldts) in october 2014, there has been a flurry of responses from commercial and hospital-based laboratory directors, clinicians, professional organizations, and diagnostic companies. the fda defines an ldt as an "in vitrodiagnostic device that is intended for clinical use and is designed, manufactured, and used within a single laboratory." the draft guidance outlines a risk-b ...201626791369
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