Publications

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 ...	2016	26784959
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 ...	2016	26527648
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 ...	2016	26798436
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 ...	2016	26763701
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 ...	2016	26751186
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 ...	2016	26751210
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 ...	2016	26869441
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 ...	2016	27965938
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 ...	2016	27818662
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 ...	2016	27193039
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 ...	2016	27114465
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 ...	2016	27148089
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 ...	2016	26791369
balance between coiled-coil stability and dynamics regulates activity of bvgs sensor kinase in bordetella.	the two-component system bvgas controls the expression of the virulence regulon of bordetella pertussis. bvgs is a prototype of bacterial sensor kinases with extracytoplasmic venus flytrap perception domains. following its transmembrane segment, bvgs harbors a cytoplasmic per-arnt-sim (pas) domain and then a predicted 2-helix coiled coil that precede the dimerization-histidine-phosphotransfer domain of the kinase. bvgs homologs have a similar domain organization, or they harbor only a predicted ...	2016	26933056
surface proteoglycans as mediators in bacterial pathogens infections.	infectious diseases remain an important global health problem. the interaction of a wide range of pathogen bacteria with host cells from many different tissues is frequently mediated by proteoglycans. these compounds are ubiquitous complex molecules which are not only involved in adherence and colonization, but can also participate in other steps of pathogenesis. to overcome the problem of microbial resistance to antibiotics new therapeutic agents could be developed based on the characteristics ...	2016	26941735
neisseria meningitidis translation elongation factor p and its active-site arginine residue are essential for cell viability.	translation elongation factor p (ef-p), a ubiquitous protein over the entire range of bacterial species, rescues ribosomal stalling at consecutive prolines in proteins. in escherichia coli and salmonella enterica, the post-translational β-lysyl modification of lys34 of ef-p is important for the ef-p activity. the β-lysyl ef-p modification pathway is conserved among only 26-28% of bacteria. recently, it was found that the shewanella oneidensis and pseudomonas aeruginosa ef-p proteins, containing ...	2016	26840407
epigenetic segregation of microbial genomes from complex samples using restriction endonucleases hpaii and mcrb.	we describe continuing work to develop restriction endonucleases as tools to enrich targeted genomes of interest from diverse populations. two approaches were developed in parallel to segregate genomic dna based on cytosine methylation. first, the methyl-sensitive endonuclease hpaii was used to bind non-cg methylated dna. second, a truncated fragment of mcrb was used to bind cpg methylated dna. enrichment levels of microbial genomes can exceed 100-fold with hpaii allowing improved genomic detect ...	2016	26727463
mglc, a paralog of myxococcus xanthus gtpase-activating protein mglb, plays a divergent role in motility regulation.	in order to optimize interactions with their environment and one another, bacteria regulate their motility. in the case of the rod-shaped cells of myxococcus xanthus, regulated motility is essential for social behaviors. m. xanthus moves over surfaces using type iv pilus-dependent motility and gliding motility. these two motility systems are coordinated by a protein module that controls cell polarity and consists of three polarly localized proteins, the small g protein mgla, the cognate mgla gtp ...	2016	26574508
genome-wide discovery of putative srnas in paracoccus denitrificans expressed under nitrous oxide emitting conditions.	nitrous oxide (n2o) is a stable, ozone depleting greenhouse gas. emissions of n2o into the atmosphere continue to rise, primarily due to the use of nitrogen-containing fertilizers by soil denitrifying microbes. it is clear more effective mitigation strategies are required to reduce emissions. one way to help develop future mitigation strategies is to address the currently poor understanding of transcriptional regulation of the enzymes used to produce and consume n2o. with this ultimate aim in mi ...	2016	27895629
a t4ss effector targets host cell alpha-enolase contributing to brucella abortus intracellular lifestyle.	brucella abortus, the causative agent of bovine brucellosis, invades and replicates within cells inside a membrane-bound compartment known as the brucella containing vacuole (bcv). after trafficking along the endocytic and secretory pathways, bcvs mature into endoplasmic reticulum-derived compartments permissive for bacterial replication. brucella type iv secretion system (virb) is a major virulence factor essential for the biogenesis of the replicative organelle. upon infection, brucella uses t ...	2016	27900285
mechanism and function of type iv secretion during infection of the human host.	bacterial pathogens employ type iv secretion systems (t4sss) for various purposes to aid in survival and proliferation in eukaryotic hosts. one large t4ss subfamily, the conjugation systems, confers a selective advantage to the invading pathogen in clinical settings through dissemination of antibiotic resistance genes and virulence traits. besides their intrinsic importance as principle contributors to the emergence of multiply drug-resistant "superbugs," detailed studies of these highly tractab ...	2016	27337453
phosphotransferase-dependent accumulation of (p)ppgpp in response to glutamine deprivation in caulobacter crescentus.	the alarmone (p)ppgpp is commonly used by bacteria to quickly respond to nutrient starvation. although (p)ppgpp synthetases such as spot have been extensively studied, little is known about the molecular mechanisms stimulating alarmone synthesis upon starvation. here, we describe an essential role of the nitrogen-related phosphotransferase system (pts(ntr)) in controlling (p)ppgpp accumulation in caulobacter crescentus. we show that cells sense nitrogen starvation by way of detecting glutamine d ...	2016	27109061
identification of ybey-protein interactions involved in 16s rrna maturation and stress regulation in escherichia coli.	ybey is part of a core set of rnases in escherichia coli and other bacteria. this highly conserved endoribonuclease has been implicated in several important processes such as 16s rrna 3' end maturation, 70s ribosome quality control, and regulation of mrnas and small noncoding rnas, thereby affecting cellular viability, stress tolerance, and pathogenic and symbiotic behavior of bacteria. thus, ybey likely interacts with numerous protein or rna partners that are involved in various aspects of cell ...	2016	27834201
quantitative proteomic analysis of shigella flexneri and shigella sonnei generalized modules for membrane antigens (gmma) reveals highly pure preparations.	outer membrane blebs are naturally shed by gram-negative bacteria and are candidates of interest for vaccines development. genetic modification of bacteria to induce hyperblebbing greatly increases the yield of blebs, called generalized modules for membrane antigens (gmma). the composition of the gmma from hyperblebbing mutants of shigella flexneri 2a and shigella sonnei were quantitatively analyzed using high-sensitivity mass spectrometry with the label-free ibaq procedure and compared to the c ...	2016	26746581
nitrogen fixation and molecular oxygen: comparative genomic reconstruction of transcription regulation in alphaproteobacteria.	biological nitrogen fixation plays a crucial role in the nitrogen cycle. an ability to fix atmospheric nitrogen, reducing it to ammonium, was described for multiple species of bacteria and archaea. the transcriptional regulatory network for nitrogen fixation was extensively studied in several representatives of the class alphaproteobacteria. this regulatory network includes the activator of nitrogen fixation nifa, working in tandem with the alternative sigma-factor rpon as well as oxygen-respons ...	2016	27617010
hijacking complement regulatory proteins for bacterial immune evasion.	the human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. in addition, formation of the membrane attack complex is responsible for direct killing of gram-negative bacteria. in turn, bacteria have evolved several ways to evade complement activation o ...	2016	28066340
modulating endotoxin activity by combinatorial bioengineering of meningococcal lipopolysaccharide.	neisseria meningitidis contains a very potent hexa-acylated lps that is too toxic for therapeutic applications. we used systematic molecular bioengineering of meningococcal lps through deletion of biosynthetic enzymes in combination with induction of lps modifying enzymes to yield a variety of novel lps mutants with changes in both lipid a acylation and phosphorylation. mass spectrometry was used for detailed compositional determination of the lps molecular species, and stimulation of immune cel ...	2016	27841285
ifnγ is required for optimal antibody-mediated immunity against genital chlamydia infection.	defining the mechanisms of immunity conferred by the combination of antibody and cd4(+) t cells is fundamental to designing an efficacious chlamydial vaccine. using the chlamydia muridarum genital infection model of mice, which replicates many features of human c. trachomatis infection and avoids the characteristic low virulence of c. trachomatis in the mouse, we previously demonstrated a significant role for antibody in immunity to chlamydial infection. we found that antibody alone was not prot ...	2016	27600502
tularemia vaccine development: paralysis or progress?	francisella tularensis (ft) is a gram-negative intercellular pathogen and category a biothreat agent. however, despite 15 years of strong government investment and intense research focused on the development of a us food and drug administration-approved vaccine against ft, the primary goal remains elusive. this article reviews research efforts focused on developing an ft vaccine, as well as a number of important factors, some only recently recognized as such, which can significantly impact the d ...	2016	27200274
listeria monocytogenes and the inflammasome: from cytosolic bacteriolysis to tumor immunotherapy.	inflammasomes are cytosolic innate immune surveillance systems that recognize a variety of danger signals, including those from pathogens. listeria monocytogenes is a gram-positive intracellular bacterium evolved to live within the harsh environment of the host cytosol. further, l. monocytogenes can activate a robust cell-mediated immune response that is being harnessed as an immunotherapeutic platform. access to the cytosol is critical for both causing disease and inducing a protective immune r ...	2016	27460808
differential responses of pattern recognition receptors to outer membrane vesicles of three periodontal pathogens.	highly purified outer membrane vesicles (omvs) of the periodontal pathogens, porphyromonas gingivalis, treponema denticola and tannerella forsythia were produced using tangential flow ultrafiltration, ultracentrifugation and optiprep density gradient separation. cryo-tem and light scattering showed omvs to be single lipid-bilayers with modal diameters of 75 to 158 nm. enumeration of omvs by nanoparticle flow-cytometry at the same stage of late exponential culture indicated that p. gingivalis was ...	2016	27035339
phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer.	apoptosis is an evolutionarily conserved and tightly regulated cell death modality. it serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. over the past decades, the molecula ...	2016	26915293
whole genome sequencing revealed host adaptation-focused genomic plasticity of pathogenic leptospira.	leptospirosis, caused by pathogenic leptospira spp., has recently been recognized as an emerging infectious disease worldwide. despite its severity and global importance, knowledge about the molecular pathogenesis and virulence evolution of leptospira spp. remains limited. here we sequenced and analyzed 102 isolates representing global sources. a high genomic variability were observed among different leptospira species, which was attributed to massive gene gain and loss events allowing for adapt ...	2016	26833181
conserved patterns of microbial immune escape: pathogenic microbes of diverse origin target the human terminal complement inhibitor vitronectin via a single common motif.	pathogenicity of many microbes relies on their capacity to resist innate immunity, and to survive and persist in an immunocompetent human host microbes have developed highly efficient and sophisticated complement evasion strategies. here we show that different human pathogens including gram-negative and gram-positive bacteria, as well as the fungal pathogen candida albicans, acquire the human terminal complement regulator vitronectin to their surface. by using truncated vitronectin fragments we ...	2016	26808444
comparative methylome analysis of the occasional ruminant respiratory pathogen bibersteinia trehalosi.	we examined and compared both the methylomes and the modification-related gene content of four sequenced strains of bibersteinia trehalosi isolated from the nasopharyngeal tracts of nebraska cattle with symptoms of bovine respiratory disease complex. the methylation patterns and the encoded dna methyltransferase (mtase) gene sets were different between each strain, with the only common pattern being that of dam (gatc). among the observed patterns were three novel motifs attributable to type i re ...	2016	27556252
salmonella typhimurium utilizes a t6ss-mediated antibacterial weapon to establish in the host gut.	the mammalian gastrointestinal tract is colonized by a high-density polymicrobial community where bacteria compete for niches and resources. one key competition strategy includes cell contact-dependent mechanisms of interbacterial antagonism, such as the type vi secretion system (t6ss), a multiprotein needle-like apparatus that injects effector proteins into prokaryotic and/or eukaryotic target cells. however, the contribution of t6ss antibacterial activity during pathogen invasion of the gut ha ...	2016	27503894
dynamic duo-the salmonella cytolethal distending toxin combines adp-ribosyltransferase and nuclease activities in a novel form of the cytolethal distending toxin.	the cytolethal distending toxin (cdt) is a well characterized bacterial genotoxin encoded by several gram-negative bacteria, including salmonella enterica (s. enterica). the cdt produced by salmonella (s-cdt) differs from the cdt produced by other bacteria, as it utilizes subunits with homology to the pertussis and subtilase toxins, in place of the traditional cdta and cdtc subunits. previously, s-cdt was thought to be a unique virulence factor of s. enterica subspecies enterica serotype typhi, ...	2016	27120620
virb8-like protein trah is crucial for dna transfer in enterococcus faecalis.	untreatable bacterial infections caused by a perpetual increase of antibiotic resistant strains represent a serious threat to human healthcare in the 21(st) century. conjugative dna transfer is the most important mechanism for antibiotic resistance and virulence gene dissemination among bacteria and is mediated by a protein complex, known as type iv secretion system (t4ss). the core of the t4ss is a multiprotein complex that spans the bacterial envelope as a channel for macromolecular secretion. ...	2016	27103580
glycoengineered outer membrane vesicles: a novel platform for bacterial vaccines.	the world health organization has indicated that we are entering into a post-antibiotic era in which infections that were routinely and successfully treated with antibiotics can now be lethal due to the global dissemination of multidrug resistant strains. conjugate vaccines are an effective way to create a long-lasting immune response against bacteria. however, these vaccines present many drawbacks such as slow development, high price, and batch-to-batch inconsistencies. alternate approaches for ...	2016	27103188
structural modeling of the flagellum ms ring protein flif reveals similarities to the type iii secretion system and sporulation complex.	the flagellum is a large proteinaceous organelle found at the surface of many bacteria, whose primary role is to allow motility through the rotation of a long extracellular filament. it is an essential virulence factor in many pathogenic species, and is also a priming component in the formation of antibiotic-resistant biofilms. the flagellum consists of the export apparatus on the cytosolic side; the basal body and rotor, spanning the bacterial membrane(s) and periplasm; and the hook-filament, t ...	2016	26925337
removal of fecal indicators, pathogenic bacteria, adenovirus, cryptosporidium and giardia (oo)cysts in waste stabilization ponds in northern and eastern australia.	maturation ponds are used in rural and regional areas in australia to remove the microbial loads of sewage wastewater, however, they have not been studied intensively until present. using a combination of culture-based methods and quantitative real-time pcr, we assessed microbial removal rates in maturation ponds at four waste stabilization ponds (wsp) with (n = 1) and without (n = 3) baffles in rural and remote communities in australia. concentrations of total coliforms, e. coli, enterococci, c ...	2016	26729150
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.	2016	27776489
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 ...	2016	27629751
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.	2016	27043012
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 ...	2016	27191004
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 ...	2016	26763966
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 ...	2016	26884414
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 ...	2016	26806181
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 ...	2016	27780200
co-regulation of iron metabolism and virulence associated functions by iron and xibr, a novel iron binding transcription factor, in the plant pathogen xanthomonas.	abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the environment. in many bacteria the ferric uptake regulator (fur) functions as transcription factor that utilize ferrous form of iron as cofactor to regulate transcription of iron me ...	2016	27902780
the mosaic type iv secretion systems.	escherichia coli and other gram-negative and -positive bacteria employ type iv secretion systems (t4sss) to translocate dna and protein substrates, generally by contact-dependent mechanisms, to other cells. the t4sss functionally encompass two major subfamilies, the conjugation systems and the effector translocators. the conjugation systems are responsible for interbacterial transfer of antibiotic resistance genes, virulence determinants, and genes encoding other traits of potential benefit to t ...	2016	27735785
crystal structure of bacterial haem importer complex in the inward-facing conformation.	pathogenic bacteria remove iron from the haem of host tissues and use it as a catalytic center of many enzymes. haem uptake by pathogenic bacteria is facilitated by the membrane-integrated haem importer, which belongs to the type ii atp-binding cassette (abc) transporter. here we present crystal structures of burkholderia cenocepacia haem importer bhuuv complexed with the periplasmic haem-binding protein bhut and in the absence of bhut. the transmembrane helices of these structures show an inwar ...	2016	27830695
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 ...	2016	27473951
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.	2016	27246403
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 ...	2016	27118638
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.	2016	26927306
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 ...	2016	26857276
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, ...	2016	26750996
interferon control of the sterol metabolic network: bidirectional molecular circuitry-mediating host protection.	the sterol metabolic network is emerging center stage in inflammation and immunity. historically, observational clinical studies show that hypocholesterolemia is a common side effect of interferon (ifn) treatment. more recently, comprehensive systems-wide investigations of the macrophage ifn response reveal a direct molecular link between cholesterol metabolism and infection. upon infection, flux through the sterol metabolic network is acutely moderated by the ifn response at multiple regulatory ...	2016	28066443
tolerogenic plasmacytoid dendritic cells control paracoccidioides brasiliensis infection by inducting regulatory t cells in an ido-dependent manner.	plasmacytoid dendritic cells (pdcs), considered critical for immunity against viruses, were recently associated with defense mechanisms against fungal infections. however, the immunomodulatory function of pdcs in pulmonary paracoccidiodomycosis (pcm), an endemic fungal infection of latin america, has been poorly defined. here, we investigated the role of pdcs in the pathogenesis of pcm caused by the infection of 129sv mice with 1 x 106 p. brasiliensis-yeasts. in vitro experiments showed that p. ...	2016	27992577
vaccination in hajj: an overview of the recent findings.	about two million people annually travel to kingdom of saudi arabia to perform hajj. the pilgrims may be at risk of exposure to communicable diseases in this mass gathering and their vaccination against contagious diseases can prevent many morbidities and mortalities. the aim of our study was to review the papers which evaluated effectiveness and compliance of the vaccines applied in hajj.	2016	28105294
otopathogenic pseudomonas aeruginosa enters and survives inside macrophages.	otitis media (om) is a broad term describing a group of infectious and inflammatory disorders of the middle ear. despite antibiotic therapy, acute om can progress to chronic suppurative otitis media (csom) characterized by ear drum perforation and purulent discharge. pseudomonas aeruginosa is the most common pathogen associated with csom. although, macrophages play an important role in innate immune responses but their role in the pathogenesis of p. aeruginosa-induced csom is not known. the obje ...	2016	27917157
microorganisms causing community-acquired acute bronchitis: the role of bacterial infection.	although acute bronchitis is quite common, there is relatively limited information regarding the microorganisms that are involved in this illness.	2016	27788254
non-culture methods for detecting infection.		2016	27789929
etiology of influenza-like illnesses from sentinel network practitioners in réunion island, 2011-2012.	in réunion island, despite an influenza surveillance established since 1996 by the sentinel general practitioner's network, little is known about the etiology of influenza like-illness (ili) that differs from influenza viruses in a tropical area. we set up a retrospective study using nasal swabs collected by sentinel gps from ili patients in 2011 and 2012. a total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (rt-pcr) including rese ...	2016	27654509
prevalence and seasonal distribution of respiratory viruses during the 2014 - 2015 season in istanbul.	acute respiratory tract infection (arti) is one of the most common infections worldwide, causing significant morbidity and mortality.	2016	27800148
epidemiology and clinical characteristics of respiratory syncytial virus infections among children and adults in mexico.	respiratory syncytial virus (rsv) is a leading etiological agent of acute respiratory tract infections and hospitalizations in children. however, little information is available regarding rsv infections in latin american countries, particularly among adult patients.	2016	27439650
epidemiology and clinical characteristics of respiratory syncytial virus infections among children and adults in mexico.	respiratory syncytial virus (rsv) is a leading etiological agent of acute respiratory tract infections and hospitalizations in children. however, little information is available regarding rsv infections in latin american countries, particularly among adult patients.	2016	27439650
clinical evaluation of the new high-throughput luminex nxtag respiratory pathogen panel assay for multiplex respiratory pathogen detection.	a broad range of viral and bacterial pathogens can cause acute respiratory tract infection. for rapid detection of a broad respiratory pathogen spectrum, multiplex real-time pcr is ideal. this study evaluated the performance of the new luminex nxtag respiratory pathogen panel (nxtag-rpp) in comparison with the biofire filmarray respiratory panel (fa-rp) or singleplex real-time pcr as reference. a total of 284 clinical respiratory specimens and 3 influenza a/h7n9 viral culture samples were tested ...	2016	27122380
derivation and multicenter validation of the drug resistance in pneumonia clinical prediction score.	the health care-associated pneumonia (hcap) criteria have a limited ability to predict pneumonia caused by drug-resistant bacteria and favor the overutilization of broad-spectrum antibiotics. we aimed to derive and validate a clinical prediction score with an improved ability to predict the risk of pneumonia due to drug-resistant pathogens compared to that of hcap criteria. a derivation cohort of 200 microbiologically confirmed pneumonia cases in 2011 and 2012 was identified retrospectively. ris ...	2016	26856838
the standard of care of patients with ards: ventilatory settings and rescue therapies for refractory hypoxemia.	severe ards is often associated with refractory hypoxemia, and early identification and treatment of hypoxemia is mandatory. for the management of severe ards ventilator settings, positioning therapy, infection control, and supportive measures are essential to improve survival.	2016	27040102
risk factors for long-term mortality after hospitalization for community-acquired pneumonia: a 5-year prospective follow-up study.	contributors to long-term mortality in patients with community-acquired pneumonia (cap) remain unclear, with little attention paid to pneumonia etiology. we examined long-term survival, causes of death, and risk factors for long-term mortality in adult patients who had been hospitalized for cap, with emphasis on demographic, clinical, laboratory, and microbiological characteristics.	2016	26849359
bacterial secretion systems: an overview.	bacterial pathogens utilize a multitude of methods to invade mammalian hosts, damage tissue sites, and thwart the immune system from responding. one essential component of these strategies for many bacterial pathogens is the secretion of proteins across phospholipid membranes. secreted proteins can play many roles in promoting bacterial virulence, from enhancing attachment to eukaryotic cells, to scavenging resources in an environmental niche, to directly intoxicating target cells and disrupting ...	2016	26999395
transcriptome-wide identification of hfq-associated rnas in brucella suis by deep sequencing.	recent breakthroughs in next-generation sequencing technologies have led to the identification of small noncoding rnas (srnas) as a new important class of regulatory molecules. in prokaryotes, srnas are often bound to the chaperone protein hfq, which allows them to interact with their partner mrna(s). we screened the genome of the zoonotic and human pathogen brucella suis 1330 for the presence of this class of rnas. we designed a coimmunoprecipitation strategy that relies on the use of hfq as a ...	2016	26553849
horizontal gene acquisitions, mobile element proliferation, and genome decay in the host-restricted plant pathogen erwinia tracheiphila.	modern industrial agriculture depends on high-density cultivation of genetically similar crop plants, creating favorable conditions for the emergence of novel pathogens with increased fitness in managed compared with ecologically intact settings. here, we present the genome sequence of six strains of the cucurbit bacterial wilt pathogen erwinia tracheiphila (enterobacteriaceae) isolated from infected squash plants in new york, pennsylvania, kentucky, and michigan. these genomes exhibit a high pr ...	2016	26992913
fine-tuning of amino sugar homeostasis by eiia(ntr) in salmonella typhimurium.	the nitrogen-metabolic phosphotransferase system, pts(ntr), consists of the enzymes i(ntr), npr and iia(ntr) that are encoded by ptsp, ptso, and ptsn, respectively. due to the proximity of ptso and ptsn to rpon, the pts(ntr) system has been postulated to be closely related with nitrogen metabolism. to define the correlation between pts(ntr) and nitrogen metabolism, we performed ligand fishing with eiia(ntr) as a bait and revealed that d-glucosamine-6-phosphate synthase (glms) directly interacted ...	2016	27628932
substrate and cofactor range differences of two cysteine dioxygenases from ralstonia eutropha h16.	cysteine dioxygenases (cdos), which catalyze the sulfoxidation of cysteine to cysteine sulfinic acid (csa), have been extensively studied in eukaryotes because of their roles in several diseases. in contrast, only a few prokaryotic enzymes of this type have been investigated. in ralstonia eutropha h16, two cdo homologues (cdoa and cdob) have been identified previously. in vivo studies showed that escherichia coli cells expressing cdoa could convert 3-mercaptopropionate (3mp) to 3-sulfinopropiona ...	2016	26590284
burkholderia contaminans biofilm regulating operon and its distribution in bacterial genomes.	biofilm formation by burkholderia spp. is a principal cause of lung chronic infections in cystic fibrosis patients. a "lacking biofilm production" (lbp) strain b. contaminans gimc4587:bct370-19 has been obtained by insertion modification of clinical strain with plasposon mutagenesis. it has an interrupted transcriptional response regulator (rr) gene. the focus of our investigation was a two-component signal transduction system determination, including this rr. b. contaminans clinical and lbp str ...	2016	28070515
linocin and ompw are involved in attachment of the cystic fibrosis-associated pathogen burkholderia cepacia complex to lung epithelial cells and protect mice against infection.	members of the burkholderia cepacia complex (bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (cf), resulting in a gradual lung function decline and, ultimately, patient death. the bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. we developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of bcc bacteria to lung epithel ...	2016	26902727
application of omics technologies for evaluation of antibacterial mechanisms of action of plant-derived products.	in the face of increasing bacterial resistance to antibiotics currently in use, the search for new antimicrobial agents has received a boost in recent years, with natural products playing an important role in this field. in fact, several methods have been proposed to investigate the antibacterial activities of natural products. however, given that the ultimate aim is future therapeutic use as novel drugs, it is extremely necessary to elucidate their modes of action, stating the molecular effects ...	2016	27729901
sensitivity of pseudomonas syringae to bovine lactoferrin hydrolysates and identification of a novel inhibitory peptide.	the antimicrobial activity of bovine lactoferrin hydrolysates (blfh) was measured against pseudomonas strains (p. syringae and p. fluorescens) in vitro. to compare susceptibility to blfh, minimal inhibitory concentration (mic) values were determined using chemiluminescence assays and paper disc plate assays. antimicrobial effect against p. fluorescens was not observed by either assay, suggesting that blfh did not exhibit antimicrobial activity against p. fluorescens. however, a significant inhib ...	2016	27621689
pseudomonas fluorescens filamentous hemagglutinin, an iron-regulated protein, is an important virulence factor that modulates bacterial pathogenicity.	pseudomonas fluorescens is a common bacterial pathogen to a wide range of aquaculture animals including various species of fish. in this study, we employed proteomic analysis and identified filamentous hemagglutinin (fha) as an iron-responsive protein secreted by tss, a pathogenic p. fluorescens isolate. in vitro study showed that compared to the wild type, the fha mutant tssfha (i) exhibited a largely similar vegetative growth profile but significantly retarded in the ability of biofilm growth ...	2016	27602029
pcr-independent detection of bacterial species-specific 16s rrna at 10 fm by a pore-blockage sensor.	a pcr-free, optics-free device is used for the detection of escherichia coli (e. coli) 16s rrna at 10 fm, which corresponds to ~100-1000 colony forming units/ml (cfu/ml) depending on cellular rrna levels. the development of a rapid, sensitive, and cost-effective nucleic acid detection platform is sought for the detection of pathogenic microbes in food, water and body fluids. since 16s rrna sequences are species specific and are present at high copy number in viable cells, these nucleic acids off ...	2016	27455337
the impact of selection, gene conversion, and biased sampling on the assessment of microbial demography.	recent studies have linked demographic changes and epidemiological patterns in bacterial populations using coalescent-based approaches. we identified 26 studies using skyline plots and found that 21 inferred overall population expansion. this surprising result led us to analyze the impact of natural selection, recombination (gene conversion), and sampling biases on demographic inference using skyline plots and site frequency spectra (sfs). forward simulations based on biologically relevant param ...	2016	26931140
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 ...	2016	27838671
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.	2016	28058402
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 ...	2016	27620673
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 ...	2016	27448237
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.	2016	26906206
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 ...	2016	26884180
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 ...	2016	26828590
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 ...	2016	27838666
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.	2016	27838668
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.	2016	27488917
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.	2016	27729960
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 ...	2016	27121506
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 ...	2016	27273824
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 ...	2016	26906904
whooping cough: identification, assessment and management.	although there is a high uptake of vaccinations providing protection against bordetella pertussis, the main cause of whooping cough, there has been an increase in the incidence of notifications of the disease in the uk and other developed countries in recent years. the increase in cases of whooping cough is mainly evident in older children and adults. while these individuals may experience persistent and unpleasant symptoms, most notably prolonged cough, symptoms may be mild, in part, because mo ...	2016	24219484
toll-like receptor 4 orchestrates neutrophil recruitment into airways during the first hours of bordetella pertussis infection.	most of the knowledge on the impact of bordetella pertussis lipo-oligosaccharide (los) on the infectious process was obtained when the bacteria was established within the host. the aim of the present work was to determine the role of tlr4 at a very early step of the infectious process. to this end we used a transcriptomic approach on b. pertussis intranasal infection model in c3h/hen, a tlr4-competent mouse strain, and c3h/hej, a tlr4-deficient mouse strain. the expression of approximately 140 g ...	2016	23811096