Publications

the association of virulence factors with genomic islands.	it has been noted that many bacterial virulence factor genes are located within genomic islands (gis; clusters of genes in a prokaryotic genome of probable horizontal origin). however, such studies have been limited to single genera or isolated observations. we have performed the first large-scale analysis of multiple diverse pathogens to examine this association. we additionally identified genes found predominantly in pathogens, but not non-pathogens, across multiple genera using 631 complete b ...	2009	19956607
phasevarions mediate random switching of gene expression in pathogenic neisseria.	many host-adapted bacterial pathogens contain dna methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible on/off switching of gene expression). in haemophilus influenzae, the random switching of the moda gene controls expression of a phase-variable regulon of genes (a "phasevarion"), via differential methylation of the genome in the moda on and off states. phase-variable mod genes are also present in neisseria meningitidis and neisseria gonorrhoeae ...	2009	19390608
biogenesis of bacterial membrane vesicles.	membrane vesicle (mv) release remains undefined, despite its conservation among replicating gram-negative bacteria both in vitro and in vivo. proteins identified in salmonella mvs, derived from the envelope, control mv production via specific defined domains that promote outer membrane protein-peptidoglycan (om-pg) and om protein-inner membrane protein (om-pg-im) interactions within the envelope structure. modulation of om-pg and om-pg-im interactions along the cell body and at division septa, r ...	2009	19432795
relative contributions of recombination and mutation to the diversification of the opa gene repertoire of neisseria gonorrhoeae.	to understand the rates and mechanisms of neisseria gonorrhoeae opa gene variation, the 11 opa genes were amplified independently so that an opa allelic profile could be defined for any isolate from the sequences at each locus. the opa allelic profiles from 14 unrelated isolates were all different, with no opa alleles shared between isolates. examination of very closely related isolates from sexual contacts and sexual networks showed that these typically shared most opa alleles, and the mechanis ...	2009	19114493
relative contributions of recombination and mutation to the diversification of the opa gene repertoire of neisseria gonorrhoeae.	to understand the rates and mechanisms of neisseria gonorrhoeae opa gene variation, the 11 opa genes were amplified independently so that an opa allelic profile could be defined for any isolate from the sequences at each locus. the opa allelic profiles from 14 unrelated isolates were all different, with no opa alleles shared between isolates. examination of very closely related isolates from sexual contacts and sexual networks showed that these typically shared most opa alleles, and the mechanis ...	2009	19114493
characterization of the meningococcal dna glycosylase fpg involved in base excision repair.	neisseria meningitidis, the causative agent of meningococcal disease, is exposed to high levels of reactive oxygen species inside its exclusive human host. the dna glycosylase fpg of the base excision repair pathway (ber) is a central player in the correction of oxidative dna damage. this study aimed at characterizing the meningococcal fpg and its role in dna repair.	2009	19134198
a common gene pool for the neisseria feta antigen.	meningococcal feta is an iron-regulated, immunogenic outer membrane protein and vaccine component. the most diverse region of this protein is a previously defined variable region (vr) that has been shown to be immunodominant. in this analysis, a total of 275 neisseria lactamica isolates, collected during studies of nasopharyngeal bacterial carriage in infants, were examined for the presence of a feta gene. the feta vr nucleotide sequence was determined for 217 of these isolates, with feta appare ...	2009	18718812
assessment of vaccine potential of the neisseria-specific protein nmb0938.	the availability of complete genome sequence of neisseria meningitidis serogroup b strain mc58 and reverse vaccinology has allowed the discovery of several novel antigens. here, we have explored the potential of n. meningitidis lipoprotein nmb0938 as a vaccine candidate, based on investigation of gene sequence conservation and the antibody response elicited after immunization in mice. this antigen was previously identified by a genome-based approach as an outer membrane lipoprotein unique to the ...	2009	19751688
biochemical and genomic analysis of the denitrification pathway within the genus neisseria.	since neisseria gonorrhoeae and neisseria meningitidis are obligate human pathogens, a comparison with commensal species of the same genus could reveal differences important in pathogenesis. the recent completion of commensal neisseria genome draft assemblies allowed us to perform a comparison of the genes involved in the catalysis, assembly and regulation of the denitrification pathway, which has been implicated in the virulence of several bacteria. all species contained a highly conserved nitr ...	2009	19762442
international external quality assurance for laboratory diagnosis of diphtheria.	the diphtheria surveillance network (dipnet) encompassing national diphtheria reference centers from 25 european countries is a dedicated surveillance network recognized by the european commission. a key dipnet objective is the quality assessment of microbiological procedures for diphtheria across the european union and beyond. a detailed questionnaire on the level of reference laboratory services and an external quality assessment (eqa) panel comprising six simulated throat specimens were sent ...	2009	19828749
evaluation of a novel real-time pcr test based on the ssra gene for the identification of group b streptococci in vaginal swabs.	despite the implementation of prevention guidelines, early-onset group b streptococci (gbs) disease remains a cause of neonatal morbidity and mortality worldwide. strategies to identify women who are at risk of transmitting gbs to their infant and the administration of intrapartum antibiotics have greatly reduced the incidence of neonatal gbs disease. however, there is a requirement for a rapid diagnostic test for gbs that can be carried out in a labour ward setting especially for women whose gb ...	2009	19732424
towards the immunoproteome of neisseria meningitidis.	despite the introduction of conjugated polysaccharide vaccines for many of the neisseria meningitidis serogroups, neisserial infections continue to cause septicaemia and meningitis across the world. this is in part due to the difficulties in developing a, cross-protective vaccine that is effective against all serogroups, including serogroup b meningococci. although convalescent n. meningitidis patients develop a natural long-lasting cross-protective immunity, the antigens that mediate this respo ...	2009	19529772
phase i safety and immunogenicity study of a candidate meningococcal disease vaccine based on neisseria lactamica outer membrane vesicles.	natural immunity to meningococcal disease in young children is associated epidemiologically with carriage of commensal neisseria species, including neisseria lactamica. we have previously demonstrated that outer membrane vesicles (omvs) from n. lactamica provide protection against lethal challenge in a mouse model of meningococcal septicemia. we evaluated the safety and immunogenicity of an n. lactamica omv vaccine in a phase i placebo-controlled, double-blinded clinical trial. ninety-seven heal ...	2009	19553555
rapid real-time pcr assays for detection of klebsiella pneumoniae with the rmpa or maga genes associated with the hypermucoviscosity phenotype: screening of nonhuman primates.	the relationship of mucoviscosity-associated (maga) and/or regulator of mucoid phenotype (rmpa) genes to the klebsiella pneumoniae hypermucoviscosity (hmv) phenotype has been reported. we previously demonstrated that rmpa+ k. pneumoniae can cause serious disease in african green monkeys and isolated rmpa+ and maga+ hmv k. pneumoniae from other species of non-human primates. to rapidly screen african green monkeys/non-human primates for these infections, we developed three real-time pcr assays. t ...	2009	19644019
epidemiological evidence for the role of the hemoglobin receptor, hmbr, in meningococcal virulence.	the distribution of the hemoglobin receptor gene (hmbr) was investigated among disease and carriage neisseria meningitidis isolates, revealing that the gene was detected at a significantly higher frequency among disease isolates than among carriage isolates. in isolates without hmbr, the locus was occupied by the cassettes exl2 or exl3 or by a "pseudo hmbr" gene, designated exl4. the hmbr locus exhibited characteristics of a pathogenicity island in published genomes of n. meningitidis, neisseria ...	2009	19476432
evidence for capsule switching between carried and disease-causing neisseria meningitidis strains.	changing antigenic structure such as with capsule polysaccharide is a common strategy for bacterial pathogens to evade a host immune system. the recent emergence of an invasive w:2a:p1.7-2,4 sequence type 11 (st-11) strain of neisseria meningitidis in new zealand, an uncommon serogroup/serotype in new zealand disease cases, was investigated for its genetic origins. molecular typing of 107 meningococcal isolates with similar serotyping characteristics was undertaken to determine genetic relations ...	2009	19451248
absence of mucosal immunity in the human upper respiratory tract to the commensal bacteria neisseria lactamica but not pathogenic neisseria meningitidis during the peak age of nasopharyngeal carriage.	the normal flora that colonizes the mucosal epithelia has evolved diverse strategies to evade, modulate, or suppress the immune system and avoid clearance. neisseria lactamica and neisseria meningitidis are closely related obligate inhabitants of the human upper respiratory tract. n. lactamica is a commensal but n. meningitidis is an opportunistic pathogen that occasionally causes invasive disease such as meningitis and septicemia. we demonstrate that unlike n. meningitidis, n. lactamica does no ...	2009	19201877
comparative analysis of two neisseria gonorrhoeae genome sequences reveals evidence of mobilization of correia repeat enclosed elements and their role in regulation.	the correia repeat enclosed element (cree) of the neisseria spp., with its inverted repeat and conserved core structure, can generate a promoter sequence at either or both ends, can bind ihf, and can bind rnase iii and either be cleaved by it or protected by it. as such, the presence of this element can directly control the expression of adjacent genes. previous work has shown differences in regulation of gene expression between neisserial strains and species due to the presence of a cree. these ...	2009	19203353
factor h-binding protein is important for meningococcal survival in human whole blood and serum and in the presence of the antimicrobial peptide ll-37.	factor h-binding protein (fhbp; gna1870) is one of the antigens of the recombinant vaccine against serogroup b neisseria meningitidis, which has been developed using reverse vaccinology and is the basis of a meningococcal b vaccine entering phase iii clinical trials. binding of factor h (fh), an inhibitor of the complement alternative pathway, to fhbp enables n. meningitidis to evade killing by the innate immune system. all fhbp null mutant strains analyzed were sensitive to killing in ex vivo h ...	2009	18852235
factor h-binding protein is important for meningococcal survival in human whole blood and serum and in the presence of the antimicrobial peptide ll-37.	factor h-binding protein (fhbp; gna1870) is one of the antigens of the recombinant vaccine against serogroup b neisseria meningitidis, which has been developed using reverse vaccinology and is the basis of a meningococcal b vaccine entering phase iii clinical trials. binding of factor h (fh), an inhibitor of the complement alternative pathway, to fhbp enables n. meningitidis to evade killing by the innate immune system. all fhbp null mutant strains analyzed were sensitive to killing in ex vivo h ...	2009	18852235
identification of meningococcal genes necessary for colonization of human upper airway tissue.	neisseria meningitidis is an exclusively human pathogen that has evolved primarily to colonize the nasopharynx rather than to cause systemic disease. colonization is the most frequent outcome following meningococcal infection and a prerequisite for invasive disease. the mechanism of colonization involves attachment of the organism to epithelial cells via bacterial type iv pili (tfp), but subsequent events during colonization remain largely unknown. we analyzed 576 n. meningitidis mutants for the ...	2009	18936183
identification of meningococcal genes necessary for colonization of human upper airway tissue.	neisseria meningitidis is an exclusively human pathogen that has evolved primarily to colonize the nasopharynx rather than to cause systemic disease. colonization is the most frequent outcome following meningococcal infection and a prerequisite for invasive disease. the mechanism of colonization involves attachment of the organism to epithelial cells via bacterial type iv pili (tfp), but subsequent events during colonization remain largely unknown. we analyzed 576 n. meningitidis mutants for the ...	2009	18936183
genomic content of neisseria species.	the physical properties of most bacterial genomes are largely unexplored. we have previously demonstrated that the strict human pathogen neisseria gonorrhoeae is polyploid, carrying an average of three chromosome copies per cell and only maintaining one pair of replication forks per chromosome (d. m. tobiason and h. s. seifert, plos biol. 4:1069-1078, 2006). we are following up this initial report to test several predictions of the polyploidy model of gonococcal chromosome organization. we demon ...	2010	20172999
filifactor alocis--involvement in periodontal biofilms.	bacteria in periodontal pockets develop complex sessile communities that attach to the tooth surface. these highly dynamic microfloral environments challenge both clinicians and researchers alike. the exploration of structural organisation and bacterial interactions within these biofilms is critically important for a thorough understanding of periodontal disease. in recent years, filifactor alocis, a fastidious, gram-positive, obligately anaerobic rod was repeatedly identified in periodontal les ...	2010	20193074
genetic, structural, and antigenic analyses of glycan diversity in the o-linked protein glycosylation systems of human neisseria species.	bacterial capsular polysaccharides and lipopolysaccharides are well-established ligands of innate and adaptive immune effectors and often exhibit structural and antigenic variability. although many surface-localized glycoproteins have been identified in bacterial pathogens and symbionts, it not clear if and how selection impacts associated glycoform structure. here, a systematic approach was devised to correlate gene repertoire with protein-associated glycoform structure in neisseria species imp ...	2010	20363948
neisseria lactamica arthritis and septicemia complicating myeloma.		2010	20410341
innate immune function of the neisserial porins and the relationship to vaccine adjuvant activity.	neisseria meningitidis is a gram-negative pathogenic bacteria responsible for bacterial meningitis and septicemia. porins are the most represented outer membrane proteins in the pathogenic neisseria species, functioning as pores for the exchange of ions, and are characterized by a trimeric beta-barrel structure. neisserial porins have been shown to act as adjuvants in the immune response via activation of b cells and other antigen-presenting cells. their effect on the immune response is mediated ...	2010	20441547
evaluation of the analytical performance of the xpert mtb/rif assay.	we performed the first studies of analytic sensitivity, analytic specificity, and dynamic range for the new xpert mtb/rif assay, a nucleic acid amplification-based diagnostic system that detects mycobacterium tuberculosis and rifampin (rif) resistance in under 2 h. the sensitivity of the assay was tested with 79 phylogenetically and geographically diverse m. tuberculosis isolates, including 42 drug-susceptible isolates and 37 rif-resistant isolates containing 13 different rpob mutations or mutat ...	2010	20504986
distinct cell death programs in monocytes regulate innate responses following challenge with common causes of invasive bacterial disease.	peripheral blood monocytes represent the rapid response component of mononuclear phagocyte host defense, generating vigorous but finite antibacterial responses. we investigated the fate of highly purified primary human monocytes following phagocytosis of different bacteria. exposure to high bacterial loads resulted in rapid loss of cell viability and decreased functional competence. cell death typically involved classical apoptosis. exposure to high numbers of escherichia coli and klebsiella pne ...	2010	20656927
characterization and pcr-based replicon typing of resistance plasmids in acinetobacter baumannii.	acinetobacter baumannii is an opportunistic pathogen, especially in intensive care units, and multidrug-resistant isolates have increasingly been reported during the last decade. despite recent progress in knowledge of antibiotic resistance mechanisms in a. baumannii, little is known about the genetic factors driving isolates toward multidrug resistance. in the present study, the a. baumannii plasmids were investigated through the analysis and classification of plasmid replication systems and th ...	2010	20660691
independent evolution of the core and accessory gene sets in the genus neisseria: insights gained from the genome of neisseria lactamica isolate 020-06.	the genus neisseria contains two important yet very different pathogens, n. meningitidis and n. gonorrhoeae, in addition to non-pathogenic species, of which n. lactamica is the best characterized. genomic comparisons of these three bacteria will provide insights into the mechanisms and evolution of pathogenesis in this group of organisms, which are applicable to understanding these processes more generally.	2010	21092259
the influence of genomics and proteomics on the development of potential vaccines against meningococcal infection.	abstract : there is a particular need for an effective vaccine against life-threatening meningitis and septicemia caused by neisseria meningitidis (meningococcus) serogroup b strains. vaccine strategies incorporating capsular polysaccharide have proved effective against other meningococcal serogroups, but are not applicable to serogroup b. attention has therefore focused on the subcapsular outer membrane protein antigens as potential vaccine components. the sequencing of genomes from three serog ...	2010	20670394
genome sequencing reveals widespread virulence gene exchange among human neisseria species.	commensal bacteria comprise a large part of the microbial world, playing important roles in human development, health and disease. however, little is known about the genomic content of commensals or how related they are to their pathogenic counterparts. the genus neisseria, containing both commensal and pathogenic species, provides an excellent opportunity to study these issues. we undertook a comprehensive sequencing and analysis of human commensal and pathogenic neisseria genomes. commensals h ...	2010	20676376
meningococcal internalization into human endothelial and epithelial cells is triggered by the influx of extracellular l-glutamate via gltt l-glutamate abc transporter in neisseria meningitidis.	meningococcal internalization into human cells is likely to be a consequence of meningococcal adhesion to human epithelial and endothelial cells. here, we identified three transposon mutants of neisseria meningitidis that were primarily defective in the internalization of human brain microvascular endothelial cells (hbmec), with insertions occurring in the gltt (a sodium-independent l-glutamate transporter) gene or its neighboring gene, nmb1964 (unknown function). nmb1964 was tentatively named g ...	2010	20956569
meningococcal internalization into human endothelial and epithelial cells is triggered by the influx of extracellular l-glutamate via gltt l-glutamate abc transporter in neisseria meningitidis.	meningococcal internalization into human cells is likely to be a consequence of meningococcal adhesion to human epithelial and endothelial cells. here, we identified three transposon mutants of neisseria meningitidis that were primarily defective in the internalization of human brain microvascular endothelial cells (hbmec), with insertions occurring in the gltt (a sodium-independent l-glutamate transporter) gene or its neighboring gene, nmb1964 (unknown function). nmb1964 was tentatively named g ...	2010	20956569
candidate vaginal microbicides with activity against chlamydia trachomatis and neisseriagonorrhoeae.	vaginal microbicides with activity towards organisms that cause sexually transmitted infections have been proposed as a strategy to reduce transmission. small-molecule inhibitors of chlamydia trachomatis serovar d belonging to the class of salicylidene acylhydrazides (inps) have been shown to work through a mechanism that involves iron restriction. expanding on this work, ten inps were tested against a lymphogranuloma venereum strain of c. trachomatis (serovar l2), neisseria gonorrhoeae, and hyd ...	2010	20605703
neisseria lactamica selectively induces mitogenic proliferation of the naive b cell pool via cell surface ig.	neisseria lactamica is a commensal bacteria that colonizes the human upper respiratory tract mucosa during early childhood. in contrast to the closely related opportunistic pathogen neisseria meningitidis, there is an absence of adaptive cell-mediated immunity to n. lactamica during the peak age of carriage. instead, outer membrane vesicles derived from n. lactamica mediate a b cell-dependent proliferative response in mucosal mononuclear cells that is associated with the production of polyclonal ...	2010	20709949
structural alterations in a component of cytochrome c oxidase and molecular evolution of pathogenic neisseria in humans.	three closely related bacterial species within the genus neisseria are of importance to human disease and health. neisseria meningitidis is a major cause of meningitis, while neisseria gonorrhoeae is the agent of the sexually transmitted disease gonorrhea and neisseria lactamica is a common, harmless commensal of children. comparative genomics have yet to yield clear insights into which factors dictate the unique host-parasite relationships exhibited by each since, as a group, they display remar ...	2010	20808844
prevalence of chlamydia infection among women visiting a gynaecology outpatient department: evaluation of an in-house pcr assay for detection of chlamydia trachomatis.	screening women for chlamydia trachomatis infection in developing countries is highly desirable because of asymptomatic infection. the existing diagnostic methods in developing countries are not effective and their sensitivity fall below 45.0% which leads to further spread of infection. there is an urgent need for improved and cost effective diagnostic tests that will reduce the burden of sexually transmitted infections in the developing world.	2010	20822551
human airway epithelial cell responses to neisseria lactamica and purified porin via toll-like receptor 2-dependent signaling.	the human airway epithelium is constantly exposed to microbial products from colonizing organisms. regulation of toll-like receptor (tlr) expression and specific interactions with bacterial ligands is thought to mitigate exacerbation of inflammatory processes induced by the commensal flora in these cells. the genus neisseria comprises pathogenic and commensal organisms that colonize the human nasopharynx. neisseria lactamica is not associated with disease, but n. meningitidis occasionally invade ...	2010	20937766
regulatory role of the misr/s two-component system in hemoglobin utilization in neisseria meningitidis.	outer membrane iron receptors are some of the major surface entities that are critical for meningococcal pathogenesis. the gene encoding the meningococcal hemoglobin receptor, hmbr, is both independently transcribed and transcriptionally linked to the upstream gene hemo, which encodes a heme oxygenase. the misr/s two-component system was previously determined to regulate hmbr transcription, and its hemo and hmbr regulatory mechanisms were characterized further here. the expression of hemo and hm ...	2010	20008531
regulatory role of the misr/s two-component system in hemoglobin utilization in neisseria meningitidis.	outer membrane iron receptors are some of the major surface entities that are critical for meningococcal pathogenesis. the gene encoding the meningococcal hemoglobin receptor, hmbr, is both independently transcribed and transcriptionally linked to the upstream gene hemo, which encodes a heme oxygenase. the misr/s two-component system was previously determined to regulate hmbr transcription, and its hemo and hmbr regulatory mechanisms were characterized further here. the expression of hemo and hm ...	2010	20008531
frequency of factor h-binding protein modular groups and susceptibility to cross-reactive bactericidal activity in invasive meningococcal isolates.	meningococcal factor h-binding protein (fhbp) is a promising vaccine candidate that elicits serum bactericidal antibodies in humans. based on sequence variability of the entire protein, fhbp has been divided into three variant groups or two sub-families. we recently reported that the fhbp architecture was modular, consisting of five variable segments, each encoded by genes from one of two lineages. based on combinations of segments from different lineages, all 70 known fhbp sequence variants cou ...	2010	20044056
frequency of factor h-binding protein modular groups and susceptibility to cross-reactive bactericidal activity in invasive meningococcal isolates.	meningococcal factor h-binding protein (fhbp) is a promising vaccine candidate that elicits serum bactericidal antibodies in humans. based on sequence variability of the entire protein, fhbp has been divided into three variant groups or two sub-families. we recently reported that the fhbp architecture was modular, consisting of five variable segments, each encoded by genes from one of two lineages. based on combinations of segments from different lineages, all 70 known fhbp sequence variants cou ...	2010	20044056
review of meningococcal group b vaccines.	no broadly effective vaccines are available for prevention of group b meningococcal disease, which accounts for >50% of all cases. the group b capsule is an autoantigen and is not a suitable vaccine target. outer-membrane vesicle vaccines appear to be safe and effective, but serum bactericidal responses in infants are specific for a porin protein, pora, which is antigenically variable. to broaden protection, outer-membrane vesicle vaccines have been prepared from >1 strain, from mutants with >1 ...	2010	20144017
conjugative plasmids of neisseria gonorrhoeae.	many clinical isolates of the human pathogen neisseria gonorrhoeae contain conjugative plasmids. the host range of these plasmids is limited to neisseria species, but presence of a tetracycline (tetm) determinant inserted in several of these plasmids is an important cause of the rapid spread of tetracycline resistance. previously plasmids with different backbones (dutch and american type backbones) and with and without different tetm determinants (dutch and american type tetm determinants) have ...	2010	20376355
neisserial omp85 protein is selectively recognized and assembled into functional complexes in the outer membrane of human mitochondria.	as a consequence of their bacterial origin, mitochondria contain β-barrel proteins in their outer membrane (omm). these proteins require the translocase of the outer membrane (tom) complex and the conserved sorting and assembly machinery (sam) complex for transport and integration into the omm. the sam complex and the β-barrel assembly machinery (bam) required for biogenesis of β-barrel proteins in bacteria are evolutionarily related. despite this homology, we show that bacterial β-barrel protei ...	2011	21652692
evaluation of six commercial nucleic acid amplification tests for the detection of neisseria gonorrhoeae and other neisseria species.	molecular detection of neisseria gonorrhoeae in extragenital samples may result in false positive results due to cross reaction with commensal neisseria species or neisseria meningitidis. this study examined 450 characterised clinical culture isolates, comprising 216 n. gonorrhoeae and 234 neisseria species (n=218) and other closely related bacteria (n=16), with six commercial nucleic acid amplification tests (naats) including gen-probe aptima combo 2 and aptima gc; roche cobas amplicor ct/ng an ...	2011	21813721
incorporation of real-time pcr into routine public health surveillance of culture negative bacterial meningitis in s+úo paulo, brazil.	real-time (rt)-pcr increases diagnostic yield for bacterial meningitis and is ideal for incorporation into routine surveillance in a developing country. we validated a multiplex rt-pcr assay for streptococcus pneumoniae, neisseria meningitidis, and haemophilus influenzae in brazil. risk factors for being culture-negative, rt-pcr positive were determined. the sensitivity of rt-pcr in cerebrospinal fluid (csf) was 100% (95% confidence limits, 96.0%-100%) for n. meningitidis, 97.8% (85.5%-99.9%) fo ...	2011	21731621
pathogenic neisseria hitchhike on the uropod of human neutrophils.	polymorphonuclear neutrophils (pmns) are important components of the human innate immune system and are rapidly recruited at the site of bacterial infection. despite the effective phagocytic activity of pmns, neisseria gonorrhoeae infections are characterized by high survival within pmns. we reveal a novel type iv pilus-mediated adherence of pathogenic neisseria to the uropod (the rear) of polarized pmns. the direct pilus-uropod interaction was visualized by scanning electron microscopy and tota ...	2011	21949708
microbial antigenic variation mediated by homologous dna recombination.	pathogenic microorganisms employ numerous molecular strategies in order to delay or circumvent recognition by the immune system of their host. one of the most widely used strategies of immune evasion is antigenic variation, in which immunogenic molecules expressed on the surface of a microorganism are continuously modified. as a consequence, the host is forced to constantly adapt its humoral immune response against this pathogen. an antigenic change thus provides the microorganism with an opport ...	2011	22212019
quantification of ploidy in proteobacteria revealed the existence of monoploid, (mero-)oligoploid and polyploid species.	bacteria are generally assumed to be monoploid (haploid). this assumption is mainly based on generalization of the results obtained with the most intensely studied model bacterium, escherichia coli (a gamma-proteobacterium), which is monoploid during very slow growth. however, several species of proteobacteria are oligo- or polyploid, respectively. to get a better overview of the distribution of ploidy levels, genome copy numbers were quantified in four species of three different groups of prote ...	2011	21305010
first report of performance of the versant ct/gc dna 1.0 assay (kpcr) for detection of chlamydia trachomatis and neisseria gonorrhoeae.	we evaluated the analytical, work flow, and clinical performance of the versant ct/gc dna 1.0 assay (versant ct/gc assay, where "ct" represents chlamydia trachomatis and "gc" represents neisseria gonorrhoeae). the assay simultaneously detects chlamydia trachomatis and neisseria gonorrhoeae in swab and first-catch urine (fcu) specimens. the limit of detection (lod) was determined to be 342 copies/ml for c. trachomatis and 137 copies/ml for gc. the versant ct/gc assay detected 15 c. trachomatis se ...	2011	21307209
cooperative role for tetraspanins in adhesin-mediated attachment of bacterial species to human epithelial cells.	the tetraspanins are a superfamily of transmembrane proteins with diverse functions and can form extended microdomains within the plasma membrane in conjunction with partner proteins, which probably includes receptors for bacterial adhesins. neisseria meningitidis, the causative agent of meningococcal disease, attaches to host nasopharyngeal epithelial cells via type iv pili and opacity (opa) proteins. we examined the role of tetraspanin function in neisseria meningitidis adherence to epithelial ...	2011	21464080
characterization of neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor h binding protein.	neisseria meningitidis remains a leading cause of bacterial sepsis and meningitis. complement is a key component of natural immunity against this important human pathogen, which has evolved multiple mechanisms to evade complement-mediated lysis. one approach adopted by the meningococcus is to recruit a human negative regulator of the complement system, factor h (fh), to its surface via a lipoprotein, factor h binding protein (fhbp). additionally, fhbp is a key antigen in vaccines currently being ...	2011	21508163
nasopharyngeal colonization by neisseria lactamica and induction of protective immunity against neisseria meningitidis.	natural immunity to neisseria meningitidis may result from nasopharyngeal carriage of closely related commensals, such as neisseria lactamica.	2011	21148522
vaccine development against neisseria meningitidis.	meningococcal disease is communicable by close contact or droplet aerosols. striking features are high case fatality rates and peak incidences of invasive disease in infants, toddlers and adolescents. vaccine development is hampered by bacterial immune evasion strategies including molecular mimicry.as for haemophilus influenzae and streptococcus pneumoniae, no vaccine has therefore been developed that targets all serogroups of neisseria meningitidis. polysaccharide vaccines available both in pro ...	2011	21255369
vaccine development against neisseria meningitidis.	meningococcal disease is communicable by close contact or droplet aerosols. striking features are high case fatality rates and peak incidences of invasive disease in infants, toddlers and adolescents. vaccine development is hampered by bacterial immune evasion strategies including molecular mimicry.as for haemophilus influenzae and streptococcus pneumoniae, no vaccine has therefore been developed that targets all serogroups of neisseria meningitidis. polysaccharide vaccines available both in pro ...	2011	21255369
from pertussis to meningococcal disease and back.	from pertussis to meningococcal disease and back represents nearly 30 years of research at porton, first at the centre for applied microbiology and research and latterly as part of the health protection agency. i joined the group lead by andy robinson developing an acellular pertussis vaccine and was part of an exciting period that encompassed basic antigen characterisation and pathogenesis studies with the development of an acellular vaccine containing fimbriae. research then changed to focus o ...	2011	21795847
human lipooligosaccharide igg that prevents endemic meningococcal disease recognizes an internal lacto-n-neotetraose structure.	antibodies that initiate complement-mediated killing of neisseria meningitidis as they enter the bloodstream from the oropharynx protect against disseminated disease. human iggs that bind the neisserial l7 lipooligosaccharide (los) are bactericidal for l3,7 and l2,4 meningococci in the presence of human complement. these strains share a lacto-n-neotetraose (nlc4) los α chain. we used a set of mutants that have successive saccharide deletions from the nlc4 α chain to characterize further the bind ...	2011	22027827
Population structure in the Neisseria, and the biological significance of fuzzy species.	Phenotypic and genetic variation in bacteria can take bewilderingly complex forms even within a single genus. One of the most intriguing examples of this is the genus Neisseria, which comprises both pathogens and commensals colonizing a variety of body sites and host species, and causing a range of disease. Complex relatedness among both named species and previously identified lineages of Neisseria makes it challenging to study their evolution. Using the largest publicly available collection of ...	2011	22072450
Population structure in the Neisseria, and the biological significance of fuzzy species.	Phenotypic and genetic variation in bacteria can take bewilderingly complex forms even within a single genus. One of the most intriguing examples of this is the genus Neisseria, which comprises both pathogens and commensals colonizing a variety of body sites and host species, and causing a range of disease. Complex relatedness among both named species and previously identified lineages of Neisseria makes it challenging to study their evolution. Using the largest publicly available collection of ...	2011	22072450
Rapid PCR detection of group A streptococcus from flocked throat swabs: a retrospective clinical study.	Rapid diagnosis of GAS pharyngitis may improve patient care by ensuring that patients with GAS pharyngitis are treated quickly and also avoiding unnecessary use of antibiotics in those without GAS infection. Very few molecular methods for detection of GAS in clinical throat swab specimens have been described.	2011	21888649
haemophilus influenzae type b carriage among young children in metropolitan atlanta in the context of vaccine shortage and booster dose deferral.	short-term deferral of the haemophilus influenzae type b (hib) vaccine booster dose during a recent u.s. hib vaccine shortage did not result in widespread hib carriage in atlanta, as the hib carriage rate was found to be 0.3% (1/342). hib colonization was significantly more common among males and day care attendees.	2011	22012977
neisserial correia repeat-enclosed elements do not influence the transcription of pil genes in neisseria gonorrhoeae and neisseria meningitidis.	two human-specific neisserial pathogens, neisseria gonorrhoeae and neisseria meningitidis, require the expression of type iv pili (tfp) for initial attachment to the host during infection. however, the mechanisms controlling the assembly and functionality of tfp are poorly understood. it is known that the gonococcal pile gene, encoding the major subunit, is positively regulated by ihf, a multifunctional dna binding protein. a neisserial specific repetitive dna sequence, termed the correia repeat ...	2011	21856854
implementation and impact of a meningococcal c conjugate vaccination program in 13- to 25-year-old individuals in galicia, spain.	background: in response to increased case numbers of meningococcal group c disease, catch-up vaccination strategies have been shown to be successful. this paper describes the results of a repeat vaccination program in galicia, spain, and the strategy used for it. methods and results: three vaccination waves were performed: first, in 1996/1997 with a meningococcal group a and c polysaccharide vaccine in individuals aged 18 months to 19 years; second, in 2000 with a conjugate serogroup c polysacc ...	2011	21957332
horizontal transfer, not duplication, drives the expansion of protein families in prokaryotes.	gene duplication followed by neo- or sub-functionalization deeply impacts the evolution of protein families and is regarded as the main source of adaptive functional novelty in eukaryotes. while there is ample evidence of adaptive gene duplication in prokaryotes, it is not clear whether duplication outweighs the contribution of horizontal gene transfer in the expansion of protein families. we analyzed closely related prokaryote strains or species with small genomes (helicobacter, neisseria, stre ...	2011	21298028
genetic and molecular analyses reveal an evolutionary trajectory for glycan synthesis in a bacterial protein glycosylation system.	although protein glycosylation systems are becoming widely recognized in bacteria, little is known about the mechanisms and evolutionary forces shaping glycan composition. species within the genus neisseria display remarkable glycoform variability associated with their o-linked protein glycosylation (pgl) systems and provide a well developed model system to study these phenomena. by examining the potential influence of two orfs linked to the core pgl gene locus, we discovered that one of these, ...	2011	21606362
francisella tularensis molecular typing using differential insertion sequence amplification (disa).	tularemia is a potentially fatal disease that is caused by the highly infectious and zoonotic pathogen francisella tularensis. despite the monomorphic nature of sequenced f. tularensis genomes, there is a significant degree of plasticity in the organization of genetic elements. the observed variability in these genomes is primarily due to the transposition of direct repeats and insertion sequence (is) elements. since current methods used to genotype f. tularensis are time-consuming and require e ...	2011	21613430
using snps to discriminate disease associated from carried genomes of neisseria meningitidis.	neisseria meningitidis is one of the main agents of bacterial meningitis causing substantial morbidity and mortality worldwide. however, most of the time n. meningitidis is carried as a commensal not associated with invasive disease. the genomic basis of the difference between disease associated versus carried isolates of n. meningitidis may provide critical insight into mechanisms of virulence, yet it has remained elusive. here, we have taken a comparative genomics approach to interrogate the d ...	2011	21622743
changes in serogroup and genotype prevalence among carried meningococci in the united kingdom during vaccine implementation.	herd immunity is important in the effectiveness of conjugate polysaccharide vaccines against encapsulated bacteria. a large multicenter study investigated the effect of meningococcal serogroup c conjugate vaccine introduction on the meningococcal population.	2011	21881120
horizontal gene transfer in histophilus somni and its role in the evolution of pathogenic strain 2336, as determined by comparative genomic analyses.	abstract: background: pneumonia and myocarditis are the most commonly reported diseases due to histophilus somni, an opportunistic pathogen of the reproductive and respiratory tracts of cattle. thus far only a few genes involved in metabolic and virulence functions have been identified and characterized in h. somni using traditional methods. analyses of the genome sequences of several pasteurellaceae species have provided insights into their biology and evolution. in view of the economic and ec ...	2011	22111657
neisseria lactamica attenuates tlr-1/2-induced cytokine responses in nasopharyngeal epithelial cells using ppar-γ.	the upper respiratory tract commensal neisseria lactamica (nlac) induces protective humoral immunity against pathogenic nmen serogroup b (nmen), but whether it also affords anti-inflammatory mucosal protection, as reported for several gut commensals, has not been investigated. here we demonstrate for the first time that nlac weakly induces inflammatory responses compared with nmen in the nasopharyngeal epithelial cell line, detroit 562, and that nlac achieves this by attenuation of secretory cyt ...	2011	21105983
genome wide expression profiling reveals suppression of host defence responses during colonisation by neisseria meningitides but not n. lactamica.	both neisseria meningitidis and the closely related bacterium neisseria lactamica colonise human nasopharyngeal mucosal surface, but only n. meningitidis invades the bloodstream to cause potentially life-threatening meningitis and septicaemia. we have hypothesised that the two neisserial species differentially modulate host respiratory epithelial cell gene expression reflecting their disease potential. confluent monolayers of 16hbe14 human bronchial epithelial cells were exposed to live and/or d ...	2011	22028815
actinomycosis and tonsillar disease.	a 10-year-old female presented with complaints of submandibular swelling, sore throat, painful deglutition, difficulty in speech and fever. the patient gave history of recurrent tonsillitis associated with snoring and breathing difficulty during sleep. oral examination revealed inflamed, hypertrophied tonsils and dental caries. throat swab culture was positive for β-haemolytic streptococci. the patient underwent elective tonsillectomy and histopathological examination revealed characteristic col ...	2011	22696708
importance of circulating antibodies in protection against meningococcal disease.	neisseria meningitidis infection results in life-threatening illnesses, including bacteremia, sepsis and meningitis. early diagnosis and treatment are a challenge due to rapid disease progression, resulting in high mortality and morbidity in survivors. disease can occur in healthy individuals, however, risk of infection is higher in patients with certain risk factors. n meningitidis carriage and case-fatality rates are high in adolescents and young adults. the absolute incidence of meningococcal ...	2012	22854672
single-cell elemental analysis of bacteria: quantitative analysis of polyphosphates in mycobacterium tuberculosis.	more than 1.8 million people die annually from infection with mycobacterium tuberculosis, the causative agent of tuberculosis. the ability of m. tuberculosis to obtain and distribute micronutrients, including biometals, is known to play a role in its intracellular survival and virulence within a host. techniques to detect elemental distributions within m. tuberculosis cells have previously been limited to bulk detection methods or low-resolution analyses. here, we present a method for determinin ...	2012	22919654
antimicrobial activities of fidaxomicin.	fidaxomicin is bactericidal against clostridium difficile. the combined results of 8 in vitro studies of 1323 c. difficile isolates showed the minimum inhibitory concentration (mic) range of fidaxomicin to be ≤ 0.001-1 μg/ml, with a maximum mic for inhibition of 90% of organisms (mic(90)) of 0.5 μg/ml. isolates from 2 phase iii clinical trials demonstrated that fidaxomicin mics of baseline isolates did not predict clinical cure, failure, or recurrence of c. difficile infections. no resistance to ...	2012	22752863
helicobacter pylori icea, clinical outcomes, and correlation with caga: a meta-analysis.	although the icea (induced by contact with epithelium) allelic types of helicobacter pylori have been reported to be associated with peptic ulcer, the importance of icea on clinical outcomes based on subsequent studies is controversial. the aim of this study was to estimate the magnitude of the risk for clinical outcomes associated with icea.	2012	22279585
various pathways leading to the acquisition of antibiotic resistance by natural transformation.	natural transformation can lead to exchange of dna between taxonomically diverse bacteria. in the case of chromosomal dna, homology-based recombination with the recipient genome is usually necessary for heritable stability. in our recent study, we have shown that natural transformation can promote the transfer of transposons, is elements, and integrons and gene cassettes, largely independent of the genetic relationship between the donor and recipient bacteria. additional results from our study s ...	2012	23482877
hypomorphic glycosyltransferase alleles and recoding at contingency loci influence glycan microheterogeneity in the protein glycosylation system of neisseria species.	as more bacterial protein glycosylation systems are identified and characterized, a central question that arises is, what governs the prevalence of particular glycans associated with them? in addition, accumulating evidence shows that bacterial protein glycans can be subject to the phenomenon of microheterogeneity, in which variant glycan structures are found at specific attachment sites of a given glycoprotein. although factors underlying microheterogeneity in reconstituted expression systems h ...	2012	22797763
growth inhibition of pathogenic bacteria by sulfonylurea herbicides.	emerging resistance to current antibiotics raises the need for new microbial drug targets. we show that targeting branched-chain amino acid (bcaa) biosynthesis using sulfonylurea herbicides, which inhibit the bcaa biosynthetic enzyme acetohydroxyacid synthase (ahas), can exert bacteriostatic effects on several pathogenic bacteria, including burkholderia pseudomallei, pseudomonas aeruginosa, and acinetobacter baumannii. our results suggest that targeting biosynthetic enzymes like ahas, which are ...	2012	23263008
identification of a unique tlr2-interacting peptide motif in a microbial leucine-rich repeat protein.	pathogenesis of many bacterially-induced inflammatory diseases is driven by toll-like receptor (tlr) mediated immune responses following recognition of bacterial factors by different tlrs. periodontitis is a chronic inflammation of the tooth supporting apparatus often leading to tooth loss, and is caused by a gram-negative bacterial consortium that includes tannerella forsythia. this bacterium expresses a virulence factor, the bspa, which drives periodontal inflammation by activating tlr2. the n ...	2012	22695115
carriage of neisseria lactamica in 1- to 29-year-old people in burkina faso: epidemiology and molecular characterization.	neisseria lactamica is a true commensal bacterium occupying the same ecological niche as the pathogenic neisseria meningitidis, which is responsible for outbreaks and large epidemics, especially in sub-saharan africa. to better understand the epidemiology of n. lactamica in africa and its relationship to n. meningitidis, we studied n. lactamica carriage in 1- to 29-year-old people living in three districts of burkina faso from 2009 to 2011. n. lactamica was detected in 18.2% of 45,847 oropharyng ...	2012	23035186
regulation of bacterial trafficking in the nasopharynx.	bacterial 'colonisation' of the nasopharynx by potential bacterial pathogens is frequent in early childhood and is frequent as part of a dynamic process in which the microbiota of the oral and nasopharynx are established. new understanding recognizes this process is evolving and that competition and likely regulation occurs among potential pathogens as well as between pathogens and commensals. such events elicit host responses that either results in clearance or persistence within the nasal and ...	2012	22726870
a bacterial siren song: intimate interactions between neisseria and neutrophils.	neisseria gonorrhoeae and neisseria meningitidis are gram-negative bacterial pathogens that are exquisitely adapted for growth at human mucosal surfaces and for efficient transmission between hosts. one factor that is essential to neisserial pathogenesis is the interaction between the bacteria and neutrophils, which are recruited in high numbers during infection. although this vigorous host response could simply reflect effective immune recognition of the bacteria, there is mounting evidence tha ...	2012	22290508
plasmid pp62bp1 isolated from an arctic psychrobacter sp. strain carries two highly homologous type ii restriction-modification systems and a putative organic sulfate metabolism operon.	the complete nucleotide sequence of plasmid pp62bp1 (34,467 bp), isolated from arctic psychrobacter sp. dab_al62b, was determined and annotated. the conserved plasmid backbone is composed of several genetic modules, including a replication system (rep) with similarities to the rep region of the iteron-containing plasmid pps10 of pseudomonas syringae. the additional genetic load of pp62bp1 includes two highly related type ii restriction-modification systems and a set of genes (slfrchsl) encoding ...	2012	22392282
a genomic approach to bacterial taxonomy: an examination and proposed reclassification of species within the genus neisseria.	in common with other bacterial taxa, members of the genus neisseria are classified using a range of phenotypic and biochemical approaches, which are not entirely satisfactory in assigning isolates to species groups. recently, there has been increasing interest in using nucleotide sequences for bacterial typing and taxonomy, but to date, no broadly accepted alternative to conventional methods is available. here, the taxonomic relationships of 55 representative members of the genus neisseria have ...	2012	22422752
evolutionary and genomic insights into meningococcal biology.	epidemic disease caused by neisseria meningitidis, the meningococcus, has been recognized for two centuries, but remains incompletely controlled and understood. there have been dramatic reductions in serogroup a and c meningococcal disease following the introduction of protein-polysaccharide conjugate vaccines, but there is currently no comprehensive vaccine against serogroup b meningococci. genetic analyses of meningococcal populations have provided many insights into the biology, evolution and ...	2012	22827308
genome sequencing of a neisseria gonorrhoeae isolate of a successful international clone with decreased susceptibility and resistance to extended-spectrum cephalosporins.	the recent emergence of neisseria gonorrhoeae strains with decreased susceptibility to extended-spectrum cephalosporins is a major concern globally. we sequenced the genome of an n. gonorrhoeae multiantigen sequence typing (ng-mast) st1407 isolate (sm-3) with decreased susceptibility and resistance to oral extended-spectrum cephalosporins. the isolate was cultured in 2008 in san francisco, ca, and possessed mosaic pena allele xxxiv, which is associated with an international clone that possesses ...	2012	22908152
can we, should we, eradicate the meningococcus?	the eradication of infectious agents is an attractive means of disease control that, to date, has been achieved for only one human pathogen, the smallpox virus. the introduction of vaccines against neisseria meningitidis into immunisation schedules, and particularly the conjugate polysaccharide vaccines which can interrupt transmission, raises the question of whether disease caused by this obligate human bacterium can be controlled, eliminated, or even eradicated. the limited number of meningoco ...	2012	22607899
analysis of the regulated transcriptome of neisseria meningitidis in human blood using a tiling array.	neisseria meningitidis is the major cause of septicemia and meningococcal meningitis. during the course of infection, the bacterium must adapt to different host environments as a crucial factor for survival and dissemination; in particular, one of the crucial factors in n. meningitidis pathogenesis is the ability to grow and survive in human blood. we recently showed that n. meningitidis alters the expression of 30% of the open reading frames (orfs) of the genome during incubation in human whole ...	2012	22984255
the amino acid sequence of neisseria lactamica porb surface-exposed loops influences toll-like receptor 2-dependent cell activation.	toll-like receptors (tlrs) play a major role in host mucosal and systemic defense mechanisms by recognizing a diverse array of conserved pathogen-associated molecular patterns (pamps). tlr2, with tlr1 and tlr6, recognizes structurally diverse bacterial products such as lipidated factors (lipoproteins and peptidoglycans) and nonlipidated proteins, i.e., bacterial porins. porb is a pan-neisserial porin expressed regardless of organisms' pathogenicity. however, commensal neisseria lactamica organis ...	2012	22825445
invasive potential of nonencapsulated disease isolates of neisseria meningitidis.	the capsule of neisseria meningitidis is the major virulence factor that enables this bacterium to overcome host immunity elicited by complement and phagocytes, rendering it capable of surviving in blood. as such, nonencapsulated n. meningitidis isolates are generally considered nonpathogenic. here, we consider the inherent virulence of two nonencapsulated n. meningitidis isolates obtained from our national surveillance of infected blood cultures in canada. capsule deficiency of both strains was ...	2012	22508859
a multiplexed microfluidic pcr assay for sensitive and specific point-of-care detection of chlamydia trachomatis.	chlamydia trachomatis (ct) is the most common cause of bacterial sexually transmitted diseases (std) worldwide. while commercial nucleic acid amplification tests (naat) are available for ct, none are rapid or inexpensive enough to be used at the point-of-care (poc). towards the first ct poc naat, we developed a microfluidic assay that simultaneously interrogates nine ct loci in 20 minutes.	2012	23272140
[congenital skull base defect causing recurrent bacterial meningitis].	bacterial meningitis is a life threatening disease. most patients will experience only one episode throughout life. children who experience bacterial meningitis more than once, require further immunologic or anatomic evaluation. we report a 9 year old child with five episodes of bacterial meningitis due to a congenital defect of the skull base. a two and a half year old boy first presented to our medical center with pneumococcal meningitis. he was treated with antibiotics and fully recovered. tw ...	2012	23350293
Distinct Roles of ß-Galactosidase Paralogues of the Rumen Bacterium Mannheimia succiniciproducens.	Mannheimia succiniciproducens, a rumen bacterium belonging to the family Pasteurellaceae, has two putative ß-galactosidase genes, bgaA and bgaB, encoding polypeptides whose deduced amino acid sequences share 56% identity with each other and show approximately 30% identity to the Escherichia coli gene for LacZ. The M. succiniciproducens bgaA (MsbgaA) gene-deletion mutant was not able to grow on lactose as the sole carbon source, suggesting its essential role in lactose metabolism, whereas the Msb ...	2012	22081396
Development of a Multiplex PCR Assay for Detection and Genogrouping of Neisseria meningitidis.	Neisseria meningitidis is a leading pathogen of epidemic bacterial meningitis and fulminant sepsis worldwide. Twelve different N. meningitidis serogroups have been identified to date based on antigenic differences in the capsular polysaccharide. However, more than 90% of human cases of N. meningitidis meningitis are the result of infection with just five serogroups, A, B, C, W135, and Y. Efficient methods of detection and genogrouping of N. meningitidis isolates are needed, therefore, in order t ...	2012	22090406
where does neisseria acquire foreign dna from: an examination of the source of genomic and pathogenic islands and the evolution of the neisseria genus.	pathogenicity islands (pais) or genomic islands (geis) are considered to be the result of a recent horizontal transfer. detecting pais/geis as well as their putative source can provide insight into the organism's pathogenicity within its host. previously we introduced a tool called s-plot which provides a visual representation of the variation in compositional properties across and between genomic sequences. utilizing s-plot and new functionality developed here, we examined 18 publicly available ...	2013	24007216
allelic variation in a simple sequence repeat element of neisserial pglb2 and its consequences for protein expression and protein glycosylation.	neisseria species express an o-linked glycosylation system in which functionally distinct proteins are elaborated with variable glycans. a major source of glycan diversity in n. meningitidis results from two distinct pglb alleles responsible for the synthesis of either n,n'-diacetylbacillosamine or glyceramido-acetamido trideoxyhexose that occupy the reducing end of the oligosaccharides. alternative modifications at c-4 of the precursor udp-4-amino are attributable to distinct c-terminal domains ...	2013	23729645