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At least 19 recordsLinked to original sources

PubMed1992

Common antigenic domains in transferrin-binding protein 2 of Neisseria meningitidis, Neisseria gonorrhoeae, and Haemophilus influenzae type b.

There is now considerable evidence to show that in the Neisseria and Haemophilus species, membrane receptors specific for either transferrin or lactoferrin are involved in the acquisition of iron from these glycoproteins. In Neisseria meningitidis, the transferrin receptor appears to consist of two proteins, one of which (TBP 1) has an M(r) of 95,000 and the other of which (TBP 2) has an M(r) ranging from 68,000 to 85,000, depending on the strain; TBP 2 binds transferrin after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting, but TBP 1 does not do so. The relative contributions of these two proteins to the binding reaction observed with intact cells and to iron uptake are presently unknown. However, they are being considered as potential components of a group B meningococcal vaccine. Analogous higher- and lower-molecular-weight proteins associated with transferrin binding have been found in N. gonorrhoeae and Haemophilus influenzae. Previous work with polyclonal antibodies raised in mice with whole cells of iron-restricted N. meningitidis showed that the meningococcal TBP 2 exhibits considerable antigenic heterogeneity. Here, we report that antiserum against purified TBP 2 from one strain of N. meningitidis cross-reacts on immunoblotting with the TBP 2 of all meningococcal isolates examined, as well as with the TBP 2 of N. gonorrhoeae. This antiserum also cross-reacted with the TBP 2 of several strains of H. influenzae type b, thus showing the presence of common antigenic domains among these functionally equivalent proteins in different pathogens; no cross-reaction was detected with a purified sample of the human transferrin receptor.

Animals↗

PubMed1995

Comparative characterization of the iga gene encoding IgA1 protease in Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae.

Cloning and sequencing of the IgA1 protease gene (iga) from Neisseria meningitidis strain HF13 showed an overall structure equivalent to iga genes from Neisseria gonorrhoeae and Haemophilus influenzae, although no region corresponding to the gonococcal alpha-peptide was evident. An additional 18 N. meningitidis and 3 H. influenzae iga genes were amplified by the polymerase chain reaction technique and sequenced corresponding approximately to the N-terminal half of the mature enzyme. Comparative analyses of a total of 29 iga genes showed that pathogenic Neisseria have iga genes with a significantly lower degree of heterogeneity than H. influenzae iga genes. Recombinational events indicated by mosaic-like structures corresponding to those found among N. gonorrhoeae protease genes were detected among N. meningitidis iga genes. One region showed characteristic differences in sequence and length which correlated with each of the different cleavage specificities. Meningococci were extremely conserved in this region with no evidence of recombination between isolates of different cleavage specificities. Sequences further downstream showed no obvious relationship with enzyme cleavage type. This region consisted of conserved areas interspersed with highly variable areas. Amino acid sequence homologies in the variable regions of meningococci reflected the antigenic types defined by using polyclonal neutralizing antibodies.

Amino Acid Sequence↗

PubMed2004

Neisseria meningitidis, Neisseria lactamica and Moraxella catarrhalis share cross-reactive carbohydrate antigens.

Carriage of commensal bacteria species is associated with the development of natural immunity to meningococcal disease, with lipo-oligosaccharides (LOS) of meningococci being one of the main virulence factors associated with severity of meningococcal disease. Meningococcal reference strains and isolates from the commensal species Neisseria lactamica and Moraxella catarrhalis were assessed for the presence of cross-reactive glycoconjugate antigens. Binding of human blood group antibodies of the P and Ii system to meningococcal immunotype reference strains were in accordance with the presence of known LOS carbohydrate structures. Binding studies with meningococcal immunotyping antibodies and blood group phenotyping antibodies to N. lactamica strains from different European countries showed, that a greater number of isolates obtained from native Greek and Scottish adults and children bound anti-meningococcal L(3, 7, 9) immunotyping (P < 0.001), pK (P = 0.035) and paragloboside (P < 0.001) blood group typing antibodies compared to isolates obtained from children of Russian immigrants in Greece. A greater number of M. catarrhalis strains isolated from children in Scotland bound anti-L(3, 7, 9) antibodies (38.2%) compared to strains isolated from adults (22.2%) (P = 0.017). These findings provide evidence that blood group like glycoconjugate antigens found on the commensal species N. lactamica and M. catarrhalis might be involved in the development of natural immunity to meningococcal endotoxins during childhood, and might be exploited as anti-meningococcal vaccine candidates.

Adolescent↗

PubMed1998

[Factors affecting Neisseria meningitidis and Neisseria lactamica carrier state].

Invasive meningococcal diseases have become in the Czech Republic since 1993 a serious epidemiological and clinical problem due to a clonus which was not present previously: Neisseria meningitidis C:2a:P1.2,P1.5, ET-15/37. In 1996 a trial was conducted focused on the problem how this altered epidemiological and clinical situation is reflected in carriership of Neisseria meningitidis and Neisseria lactamica in the healthy population. Two age groups were followed up which were most severely affected by the new clonus of the meningococcus: 15-19 years (410 subjects) and 1-4 years (116 subjects). The trial was implemented in Olomouc where in 1993 the new epidemiological situation of the incidence of the invasive meningococcal disease was so serious that targeted vaccination was introduced. Of 116 children in the age group from 1-4 years in none Neisseria meningitidis was detected, in 9 Neisseria lactamica was found (7.7%). On repeated examination of children with a positive cultivation of Neisseria lactamica after two weeks in none Neisseria meningitidis nor Neisseria lactamica were found. Of 410 subjects in the age group from 15-19 years in none Neisseria lactamica was detected and in 35 Neisseria meningitidis (8.5%). Examinations were repeated after two weeks in 33 carriers: in 31 Neisseria meningitidis was again cultivated. Analysis of factors influencing carriership revealed in Neisseria lactamica two factors in young children which significantly promote this carriership: cold and close contact/kissing. A risk factor at the limit of significance are frequent respiratory diseases. In the carriership of Neisseria meningitidis in 15-19 year-old subjects six factors were revealed which promote carriership. A significant risk factor is close contact/kissing, the existence of partnership, participation in activities of the "disco" type, living in a town, flats in the centre of the town. Effort is a risk factor at the limit of significance.

Adolescent↗

PubMed2005

Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis.

Neisseria meningitidis (meningococcus) is an important cause of meningitis and sepsis. Currently, there is no effective vaccine against serogroup B meningococcal infection. Host defense against neisseriae requires the complement system (C) as indicated by the fact that individuals deficient in properdin or late C components (C6-9) have an increased susceptibility to recurrent neisserial infections. Because the classical pathway (CP) is required to initiate efficient complement activation on neisseriae, meningococci should be able to evade it to cause disease. To test this hypothesis, we studied the interactions of meningococci with the major CP inhibitor C4b-binding protein (C4bp). We tested C4bp binding to wild-type group B meningococcus strain (H44/76) and to 11 isogenic mutants thereof that differed in capsule expression, lipo-oligosaccharide sialylation, and/or expression of either porin (Por) A or PorB3. All strains expressing PorA bound radiolabeled C4bp, whereas the strains lacking PorA bound significantly less C4bp. Increased binding was observed under hypotonic conditions. Deleting PorB3 did not influence C4bp binding, but the presence of polysialic acid capsule reduced C4bp binding by 50%. Bound C4bp remained functionally active in that it promoted the inactivation of C4b by factor I. PorA-expressing strains were also more resistant to C lysis than PorA-negative strains in a serum bactericidal assay. Binding of C4bp thus helps Neisseria meningitidis to escape CP complement activation.

Amino Acid Sequence↗

PubMed2003

Molecular epidemiology of Neisseria meningitidis.

Neisseria meningitidis poses a major disease burden on human beings. Meningococcal typing has a longstanding tradition for epidemiological surveillance of the disease. Genetic and antigenetic variability resulting from horizontal genetic exchange has been exploited for this purpose. Neisseria meningitidis served as the bacterial prototype organism for the development of multi locus sequence typing, which has replaced multi locus enzyme electrophoresis as the gold standard for meningococcal typing. Due to the rapid emergence of new porin variants serotyping by monoclonal antibodies is currently being replaced by DNA sequencing of variable regions of the porA gene. Sequence data were used to characterize the population structure of meningococci in carriage and disease. The advances in molecular epidemiology of meningococcal disease, and the rapid exchange of DNA sequence data via curated internet websites have resulted in an interactive international network, which is capable of identifying newly emerging clones within weeks.

Humans↗

PubMed2005

Viability of a capsule- and lipopolysaccharide-deficient mutant of Neisseria meningitidis.

Neisseria meningitidis is the only lipopolysaccharide (LPS)-producing gram-negative bacterial species shown to be viable also without LPS. It was thought that the presence of capsular polysaccharide is necessary for this unusual feature. However, we show now that no part of the capsule gene cluster is required for maintaining LPS deficiency in N. meningitidis.

Acyltransferases↗

PubMed2006

Intranasal immunization of mice with recombinant lipidated P2086 protein reduces nasal colonization of group B Neisseria meningitidis.

Neisseria meningitidis is a major cause of bacterial meningitis in the human population, especially among young children. There is a need to develop a non-capsular vaccine to prevent meningococcal B infections due to the inadequate immune response elicited against the capsular polysaccharide of these strains. Previously, we developed a Swiss Webster adult mouse intranasal challenge model for group B N. meningitidis and evaluated several potential vaccine candidates including a meningococcal outer membrane protein, P2086, through parenteral immunization. Since N. meningitidis is a respiratory pathogen, a mucosal immune response may play an important role in the defense against meningococcal infections. Thus, intranasal immunization may be more effective than traditional parenteral immunization. In this study, mice were immunized intranasally with purified recombinant lipidated P2086 protein (rLP2086) adjuvanted with either CT-E29H, a genetically modified cholera toxin that is significantly reduced in enzymatic activity and toxicity or RC529-AF, a synthetic immunostimulant molecule in aqueous formulation. rLP2086-specific serum and mucosal IgG and IgA antibodies were induced. IgG antibodies reacted with whole cells of multiple strains of group B N.meningitidis. The antibodies have functional activity against N. meningitidis as demonstrated by bactericidal assays. Moreover, immunized mice exhibited reduced nasal colonization of group B meningococcal strains in the intranasal challenge model. These results demonstrate that an intranasal immunization with rLP2086 protein formulated with a detoxified cholera toxin or RC529-AF could prevent the initial colonization of group B meningococcus and become an effective immunization strategy against group B N. meningitidis.

Administration, Intranasal↗

PubMed2001

Genetic analysis of conservation and variation of lipooligosaccharide expression in two L8-immunotype strains of Neisseria meningitidis.

Neisseria meningitidis strains A1 and M978 both express the lipooligosaccharide (LOS) L8 immunotype [Gu et al., J. Clin. Microbiol. 30 (1992) 2047-2053]. Under different growth conditions, strain A1 did not change its LOS profile whereas strain M978 produced variable LOS profiles on SDS-PAGE. To understand the genetic basis of LOS conservation and variation, their lgt locus encoding glycosyltransferases responsible for the biosynthesis of the alpha-chain of LOS was analyzed. Strain A1 possessed only two genes, lgtA and lgtH, at the lgt locus. The lgtA gene was inactivated due to a frameshift mutation; thus strain A1 expressed only L8 LOS. In contrast, strain M978 contained five genes lgtZ, lgtC, lgtA, lgtB and lgtE at this locus, thus it had a potential to express L1, L3,7 in addition to the L8 LOS. The data showed that strain A1 is a better reference strain for the L8 immunotype because of the stability of L8 LOS expression resulting from its unique lgt locus. In addition, these two strains had two new genetic organizations, lgtAH and lgtZCABE, compared to the reported gene organization at the lgt locus in N. meningitidis.

Bacterial Proteins↗

PubMed2002

Nitric oxide metabolism in Neisseria meningitidis.

Neisseria meningitidis, the causative agent of meningococcal disease in humans, is likely to be exposed to nitrosative stress during natural colonization and disease. The genome of N. meningitidis includes the genes aniA and norB, predicted to encode nitrite reductase and nitric oxide (NO) reductase, respectively. These gene products should allow the bacterium to denitrify nitrite to nitrous oxide. We show that N. meningitidis can support growth microaerobically by the denitrification of nitrite via NO and that norB is required for anaerobic growth with nitrite. NorB and, to a lesser extent, the cycP gene product cytochrome c' are able to counteract toxicity due to exogenously added NO. Expression of these genes by N. meningitidis during colonization and disease may confer protection against exogenous or endogenous nitrosative stress.

Aerobiosis↗

PubMed1992

Human monoclonal antibodies against an epitope on the class 5c outer membrane protein common to many pathogenic strains of Neisseria meningitidis.

Neisseria meningitidis is a causative agent of meningitis. Despite vaccination programs, it still causes a large number of deaths in young children. Early diagnosis followed by passive immunization with human monoclonal antibodies could be an approach to effective therapy. Peripheral blood lymphocytes from normal, healthy blood donors and from vaccinated individuals were immunized in vitro, using outer membrane proteins purified from N. meningitidis B:4:P1.15. The immunized human B cells were Epstein-Barr virus transformed and fused to a heteromyeloma. Several stable human hybridoma cell lines were established and two, secreting antibodies against the 31-kDa class 5c outer membrane protein, were characterized further. The human antibodies were of IgG1 and IgG3 isotypes, with kappa light chains. The recognized epitope was commonly found among pathogenic strains of N. meningitidis; thus, these human monoclonal antibodies may be important in the evaluation of N. meningitidis infections.

Animals↗

PubMed1987

Septicaemia due to Neisseria lactamica--initial confusion with Neisseria meningitidis.

Neisseria lactamica, isolated from a baby with septicaemia, was at first thought to be Neisseria meningitidis, possibly acquired in hospital. Extensive investigation of contacts was made until the O-nitrophenyl-D-galactopyranoside reaction proved positive. Distinction between the two species, easily made in this way, is important both in individual patients and in population surveys.

Bacterial Infections↗

PubMed2006

Functional significance of factor H binding to Neisseria meningitidis.

Neisseria meningitidis is an important cause of septicemia and meningitis. To cause disease, the bacterium must successfully survive in the bloodstream where it has to avoid being killed by host innate immune mechanisms, particularly the complement system. A number of pathogenic microbes bind factor H (fH), the negative regulator of the alternative pathway of complement activation, to promote their survival in vivo. In this study, we show that N. meningitidis binds fH to its surface. Binding to serogroups A, B, and C N. meningitidis strains was detected by FACS and Far Western blot analysis, and occurred in the absence of other serum factors such as C3b. Unlike Neisseria gonorrhoeae, binding of fH to N. meningitidis was independent of sialic acid on the bacterium, either as a component of its LPS or its capsule. Characterization of the major fH binding partner demonstrated that it is a 33-kDa protein; examination of insertion mutants showed that porins A and B, outer membrane porins expressed by N. meningitidis, do not contribute significantly to fH binding. We examined the physiological consequences of fH bound to the bacterial surface. We found that fH retains its activity as a cofactor of factor I when bound to the bacterium and contributes to the ability of N. meningitidis to avoid complement-mediated killing in the presence of human serum. Therefore, the recruitment of fH provides another mechanism by which this important human pathogen evades host innate immunity.

Amino Acid Sequence↗

PubMed2002

The duality of virulence and transmissibility in Neisseria meningitidis.

Neisseria meningitidis is a commensal bacterium of the human nasopharynx that occasionally provokes invasive disease. Carriage strains of N. meningitidis are heterogeneous, more frequent in nature and are transmitted among carriers. Disease is not a part of this transmission cycle and is caused by virulent strains. N. meningitidis is highly variable and variants that are modified in their virulence and/or transmissibility are continually generated. These events probably occur frequently, thus explaining not only the heterogeneous nature of meningococcal populations in carriers but probably also the evolutionary success of this human-restricted bacterium.

Carrier State↗

PubMed2001

Mismatch repair and the regulation of phase variation in Neisseria meningitidis.

Neisseria meningitidis controls the expression of several genes involved in host adaptation by a process known as phase variation. The phase variation frequency of haemoglobin (Hb) receptors among clinical isolates of serogroups A, B and C differed drastically, ranging from approximately 10(-6) to 10(-2) cfu-1. Frequencies of phase variation are a genetic trait of a particular strain, as two unlinked Hb receptors, hpuAB and hmbR, phase varied with similar frequencies within a given isolate. Based on these frequencies, six Neisserial clinical isolates could be grouped into three distinct classes; slow, medium and fast. An increase in phase variation frequency was accompanied by high rates of spontaneous mutation to rifampicin and nalidixic acid resistance in one medium and one fast strain. The remaining three medium strains displayed elevated levels of phase variation without increases in overall mutability, as they possessed low rates of spontaneous mutation to drug resistance. The mismatch repair system of N. meningitidis was found to play an important role in determining the overall mutability of the clinical isolates. Inactivation of mismatch repair in any strain, regardless of its original phenotype, increased mutability to a level seen in the fast strain. Insertional inactivation of mutS and mutL in the slow strain led to 500- and 250-fold increases in hmbR switching frequency respectively. Concurrently, the frequency of spontaneous point mutations of mutS and mutL mutants from the slow strain was increased 20- to 30-fold to the level seen in the high strain. The status of Dam methylation did not correlate with either the phase variation frequency of Hb receptors or the general mutability of Neisserial strains. Analysis of an expanded set of isolates identified defects in mismatch repair as the genetic basis for strains displaying both the fast Hb switching and high mutation rate phenotypes. In conclusion, elevated frequencies of phase variation were accompanied by increased overall mutability in some N. meningitidis isolates including strains shown to be mismatch repair defective. Other isolates have evolved mechanisms that seem to affect only the switching frequency of phase-variable genes without an accompanied increased accumulation of spontaneous mutations.

Adenosine Triphosphatases↗

PubMed2000

Epidemiology and pathogenesis of Neisseria meningitidis.

Neisseria meningitidis, an exclusive pathogen of humans, remains the leading worldwide cause of meningitis and fatal sepsis, usually in otherwise healthy individuals. In recent years, significant advances have improved our understanding of the epidemiology and genetic basis of meningococcal disease and led to progress in the development of the next generation of meningococcal vaccines. This review summarizes current knowledge of the human susceptibility to and the epidemiology and molecular pathogenesis of meningococcal disease.

Adult↗

PubMed2006

Development and characterization of a murine monoclonal antibody specific for the P1.15 PorA proteins from vaccine strain B:4,7:P1.19,15 of Neisseria meningitidis.

Neisseria meningitidis isolates are conventionally classified by serosubtyping, which characterizes the reactivities of the PorA outer membrane protein variable-region epitopes with monoclonal antibodies (MAbs). New murine hybridomas, secreting specific MAbs against PorA of N. meningitidis serogroup B, were generated using conventional hybridoma procedures. Using outer membrane protein as antigen, we obtained two positive clones, and one of them we characterized. This MAb reacted, on whole-cell enzyme-linked immunosorbent assay (ELISA) and immunoblotting, only with strain subtype P1.15 and its IgG2b isotype. This MAb demonstrated bactericidal activity against the homologous strain in the presence of human complement.

Animals↗

PubMed1999

The genetic basis of the phase variation repertoire of lipopolysaccharide immunotypes in Neisseria meningitidis.

Neisseria meningitidis strains express a diverse range of lipopolysaccharide (LPS) structures that have been classified into 12 immunotypes. A feature of meningococcal LPS is the reversible, high-frequency switching of expression (phase variation) of terminal LPS structures. A number of studies are strongly suggestive of a key role for these terminal structures, and their phase-variable expression, in pathogenesis. In a previous study, a locus of three LPS biosynthetic genes, IgtABE, involved in the biosynthesis of one of these terminal structures, lacto-N-neotetraose, was described. The molecular mechanism of phase-variable expression of this structure is by high-frequency mutation in a homopolymeric tract of G residues in the IgtA gene. To investigate the genetic basis of the structural differences between the immunotypes, and the potential for strains to express alternative immunotypes, this locus was examined in all of the immunotype strains. Initially, the Igt locus of strain 126E, an L1 immunotype strain, was cloned and sequenced, revealing two active genes, IgtC and IgtE. The remnants of the IgtA and IgtB genes and an inactive IgtD gene were also present, indicating that the locus may have once contained five active genes, similar to a locus previously reported in Neisseria gonorrhoeae strain F62. Probes based on each of the Igt genes (ABCDE), and the recently reported IgtG gene, were used to determine the presence or absence of Igt genes within individual strains, allowing the prediction of the phase variation repertoire of these strains. Sequencing to determine the nature of homopolymeric tract regions within the Igt genes was carried out to establish the potential for LPS switching. In general, the set of strains examined could be sorted into two distinct groups: one group which phase-vary the alpha-chain extension via IgtA or IgtC but cannot make beta-chain; the second group phase-vary the beta-chain extension via IgtG but do not vary alpha-chain (lacto-N-neotetraose).

Bacterial Proteins↗