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Methods in Molecular Biology (Clifton,... 2012Neisseria meningitidis (the meningococcus) causes significant morbidity and mortality in children and young adults worldwide through epidemic or sporadic meningitis... (Review)
Review
Neisseria meningitidis (the meningococcus) causes significant morbidity and mortality in children and young adults worldwide through epidemic or sporadic meningitis and/or septicemia. In this review, we describe the biology, microbiology, and epidemiology of this exclusive human pathogen. N.meningitidis is a fastidious, encapsulated, aerobic gram-negative diplococcus. Colonies are positive by the oxidase test and most strains utilize maltose. The phenotypic classification of meningococci, based on structural differences in capsular polysaccharide, lipooligosaccharide (LOS) and outer membrane proteins, is now complemented by genome sequence typing (ST). The epidemiological profile of N. meningitidis is variable in different populations and over time and virulence of the meningococcus is based on a transformable/plastic genome and expression of certain capsular polysaccharides (serogroups A, B, C, W-135, Y and X) and non-capsular antigens. N. meningitidis colonizes mucosal surfaces using a multifactorial process involving pili, twitching motility, LOS, opacity associated, and other surface proteins. Certain clonal groups have an increased capacity to gain access to the blood, evade innate immune responses, multiply, and cause systemic disease. Although new vaccines hold great promise, meningococcal infection continues to be reported in both developed and developing countries, where universal vaccine coverage is absent and antibiotic resistance increasingly more common.
Topics: Age Factors; Animals; Bacterial Capsules; Geography; Humans; Meningitis, Meningococcal; Models, Biological; Neisseria meningitidis; Phenotype; Virulence
PubMed: 21993636
DOI: 10.1007/978-1-61779-346-2_1 -
Current Opinion in Microbiology Feb 2015The recent advances in cellular microbiology, genomics, and immunology has opened new horizons in the understanding of meningococcal pathogenesis and in the definition... (Review)
Review
The recent advances in cellular microbiology, genomics, and immunology has opened new horizons in the understanding of meningococcal pathogenesis and in the definition of new prophylactic intervention. It is now clear that Neissera meningitidis has evolved a number of surface structures to mediate interaction with host cells and a number of mechanisms to subvert the immune system and escape complement-mediated killing. In this review we report the more recent findings on meningococcal adhesion and on the bacteria-complement interaction highlighting the redundancy of these mechanisms. An effective vaccine against meningococcus B, based on multiple antigens with different function, has been recently licensed. The antibodies induced by the 4CMenB vaccine could mediate bacterial killing by activating directly the classical complement pathway or, indirectly, by preventing binding of fH on the bacterial surface and interfering with colonization.
Topics: Bacterial Adhesion; Blood Bactericidal Activity; Complement System Proteins; Host-Pathogen Interactions; Immune Evasion; Meningococcal Infections; Neisseria meningitidis
PubMed: 25461575
DOI: 10.1016/j.mib.2014.11.006 -
Frontiers in Cellular and Infection... 2014A longstanding question in infection biology addresses the genetic basis for invasive behavior in commensal pathogens. A prime example for such a pathogen is Neisseria... (Review)
Review
A longstanding question in infection biology addresses the genetic basis for invasive behavior in commensal pathogens. A prime example for such a pathogen is Neisseria meningitidis. On the one hand it is a harmless commensal bacterium exquisitely adapted to humans, and on the other hand it sometimes behaves like a ferocious pathogen causing potentially lethal disease such as sepsis and acute bacterial meningitis. Despite the lack of a classical repertoire of virulence genes in N. meningitidis separating commensal from invasive strains, molecular epidemiology suggests that carriage and invasive strains belong to genetically distinct populations. In recent years, it has become increasingly clear that metabolic adaptation enables meningococci to exploit host resources, supporting the concept of nutritional virulence as a crucial determinant of invasive capability. Here, we discuss the contribution of core metabolic pathways in the context of colonization and invasion with special emphasis on results from genome-wide surveys. The metabolism of lactate, the oxidative stress response, and, in particular, glutathione metabolism as well as the denitrification pathway provide examples of how meningococcal metabolism is intimately linked to pathogenesis. We further discuss evidence from genome-wide approaches regarding potential metabolic differences between strains from hyperinvasive and carriage lineages and present new data assessing in vitro growth differences of strains from these two populations. We hypothesize that strains from carriage and hyperinvasive lineages differ in the expression of regulatory genes involved particularly in stress responses and amino acid metabolism under infection conditions.
Topics: Animals; Carbon; Carrier State; Electron Transport Chain Complex Proteins; Genome, Bacterial; Glutamic Acid; Humans; Meningitis, Meningococcal; Metabolome; Metabolomics; Nasopharynx; Neisseria meningitidis; Oxidative Stress; Transcriptome; Virulence
PubMed: 25191646
DOI: 10.3389/fcimb.2014.00114 -
Proceedings of the National Academy of... Mar 1998Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to... (Comparative Study)
Comparative Study
Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to compare among laboratories. To overcome these problems, we propose multilocus sequence typing (MLST), which exploits the unambiguous nature and electronic portability of nucleotide sequence data for the characterization of microorganisms. To evaluate MLST, we determined the sequences of approximately 470-bp fragments from 11 housekeeping genes in a reference set of 107 isolates of Neisseria meningitidis from invasive disease and healthy carriers. For each locus, alleles were assigned arbitrary numbers and dendrograms were constructed from the pairwise differences in multilocus allelic profiles by cluster analysis. The strain associations obtained were consistent with clonal groupings previously determined by multilocus enzyme electrophoresis. A subset of six gene fragments was chosen that retained the resolution and congruence achieved by using all 11 loci. Most isolates from hyper-virulent lineages of serogroups A, B, and C meningococci were identical for all loci or differed from the majority type at only a single locus. MLST using six loci therefore reliably identified the major meningococcal lineages associated with invasive disease. MLST can be applied to almost all bacterial species and other haploid organisms, including those that are difficult to cultivate. The overwhelming advantage of MLST over other molecular typing methods is that sequence data are truly portable between laboratories, permitting one expanding global database per species to be placed on a World-Wide Web site, thus enabling exchange of molecular typing data for global epidemiology via the Internet.
Topics: Bacterial Typing Techniques; Cluster Analysis; Evaluation Studies as Topic; Gene Frequency; Genes, Bacterial; Humans; Meningococcal Infections; Molecular Sequence Data; Neisseria meningitidis; Sequence Analysis, DNA; Virulence
PubMed: 9501229
DOI: 10.1073/pnas.95.6.3140 -
Current Opinion in Infectious Diseases Feb 2021Neisseria meningitidis (Nm) is primarily associated with asymptomatic nasopharyngeal carriage and invasive meningococcal disease (sepsis and meningitis), but like N.... (Review)
Review
PURPOSE OF REVIEW
Neisseria meningitidis (Nm) is primarily associated with asymptomatic nasopharyngeal carriage and invasive meningococcal disease (sepsis and meningitis), but like N. gonorrhoea (Ng), Nm can colonize urogenital and rectal mucosal surfaces and cause disease. First noted in 2015, but with origins in 2011, male urethritis clusters caused by a novel Nm clade were reported in the USA (the US_NmUC). This review describes research developments that characterize this urogenital-tropic Nm.
RECENT FINDINGS
The US_NmUC evolved from encapsulated Nm serogroup C strains. Loss of capsule expression, lipooligosaccharide (LOS) sialylation, genetic acquisition of gonococcal alleles (including the gonococcal anaerobic growth aniA/norB cassette), antimicrobial peptide heteroresistance and high surface expression of a unique factor-H-binding protein, can contribute to the urethra-tropic phenotype. Loss-of-function mutations in mtrC are overrepresented in clade isolates. Similar to Ng, repeat US_NmUC urethritis episodes can occur. The US_NmUC is now circulating in the UK and Southeast Asia. Genomic sequencing has defined the clade and rapid diagnostic tests are being developed for surveillance.
SUMMARY
The US_NmUC emerged as a cause of urethritis due to acquisition of gonococcal genetic determinants and phenotypic traits that facilitate urogenital tract infection. The epidemiology and pathogenesis of this urogenital-tropic pathogen continues to be defined.
Topics: Communicable Diseases, Emerging; Humans; Meningococcal Infections; Neisseria meningitidis; Urethritis
PubMed: 33278178
DOI: 10.1097/QCO.0000000000000697 -
Critical Reviews in Microbiology Sep 2016Neisseria meningitidis, a devastating pathogen exclusive to humans, expresses capsular polysaccharides that are the major meningococcal virulence determinants and the... (Review)
Review
Neisseria meningitidis, a devastating pathogen exclusive to humans, expresses capsular polysaccharides that are the major meningococcal virulence determinants and the basis for successful meningococcal vaccines. With rare exceptions, the expression of capsule (serogroups A, B, C, W, X, Y) is required for systemic invasive meningococcal disease. Changes in capsule expression or structure (e.g. hypo- or hyper-encapsulation, capsule "switching", acetylation) can influence immunologic diagnostic assays or lead to immune escape. The loss or down-regulation of capsule is also critical in meningococcal biology facilitating meningococcal attachment, microcolony formation and the carriage state at human mucosal surfaces. Encapsulated meningococci contain a cps locus with promoters located in an intergenic region between the biosynthesis and the conserved capsule transport operons. The cps intergenic region is transcriptionally regulated (and thus the amount of capsule expressed) by IS element insertion, by a two-component system, MisR/MisS and through sequence changes that result in post-transcriptional RNA thermoregulation. Reversible on-off phase variation of capsule expression is controlled by slipped strand mispairing of homo-polymeric tracts and by precise insertion and excision of IS elements (e.g. IS1301) in the biosynthesis operon. Capsule structure can be altered by phase-variable expression of capsular polymer modification enzymes or "switched" through transformation and homologous recombination of different polymerases. Understanding the complex regulation of meningococcal capsule has important implications for meningococcal biology, pathogenesis, diagnostics, current and future vaccine development and vaccine strategies.
Topics: Animals; Bacterial Capsules; Bacterial Proteins; Gene Expression Regulation, Bacterial; Humans; Meningococcal Infections; Neisseria meningitidis
PubMed: 26089023
DOI: 10.3109/1040841X.2015.1022507 -
Clinical Science (London, England :... Feb 2010The human species is the only natural host of Neisseria meningitidis, an important cause of bacterial meningitis globally, and, despite its association with devastating... (Review)
Review
The human species is the only natural host of Neisseria meningitidis, an important cause of bacterial meningitis globally, and, despite its association with devastating diseases, N. meningitidis is a commensal organism found frequently in the respiratory tract of healthy individuals. To date, antibiotic resistance is relatively uncommon in N. meningitidis isolates but, due to the rapid onset of disease in susceptible hosts, the mortality rate remains approx. 10%. Additionally, patients who survive meningococcal disease often endure numerous debilitating sequelae. N. meningitidis strains are classified primarily into serogroups based on the type of polysaccharide capsule expressed. In total, 13 serogroups have been described; however, the majority of disease is caused by strains belonging to one of only five serogroups. Although vaccines have been developed against some of these, a universal meningococcal vaccine remains a challenge due to successful immune evasion strategies of the organism, including mimicry of host structures as well as frequent antigenic variation. N. meningitidis express a range of virulence factors including capsular polysaccharide, lipopolysaccharide and a number of surface-expressed adhesive proteins. Variation of these surface structures is necessary for meningococci to evade killing by host defence mechanisms. Nonetheless, adhesion to host cells and tissues needs to be maintained to enable colonization and ensure bacterial survival in the niche. The aims of the present review are to provide a brief outline of meningococcal carriage, disease and burden to society. With this background, we discuss several bacterial strategies that may enable its survival in the human respiratory tract during colonization and in the blood during infection. We also examine several known meningococcal adhesion mechanisms and conclude with a section on the potential processes that may operate in vivo as meningococci progress from the respiratory niche through the blood to reach the central nervous system.
Topics: Carrier State; Host-Pathogen Interactions; Humans; Meninges; Meningococcal Infections; Nasopharynx; Neisseria meningitidis; Virulence
PubMed: 20132098
DOI: 10.1042/CS20090513 -
Frontiers in Cellular and Infection... 2017is a Gram-negative bacterial pathogen that normally resides as a commensal in the human nasopharynx but occasionally causes disease with high mortality and morbidity.... (Review)
Review
is a Gram-negative bacterial pathogen that normally resides as a commensal in the human nasopharynx but occasionally causes disease with high mortality and morbidity. To interact with its environment, it transports many proteins across the outer membrane to the bacterial cell surface and into the extracellular medium for which it deploys the common and well-characterized autotransporter, two-partner and type I secretion mechanisms, as well as a recently discovered pathway for the surface exposure of lipoproteins. The surface-exposed and secreted proteins serve roles in host-pathogen interactions, including adhesion to host cells and extracellular matrix proteins, evasion of nutritional immunity imposed by iron-binding proteins of the host, prevention of complement activation, neutralization of antimicrobial peptides, degradation of immunoglobulins, and permeabilization of epithelial layers. Furthermore, they have roles in interbacterial interactions, including the formation and dispersal of biofilms and the suppression of the growth of bacteria competing for the same niche. Here, we will review the protein secretion systems of and focus on the functions of the secreted proteins.
Topics: Bacterial Adhesion; Bacterial Outer Membrane Proteins; Bacterial Secretion Systems; Biofilms; Biological Transport; Host-Pathogen Interactions; Humans; Immune Evasion; Iron; Lipoproteins; Meningococcal Infections; Neisseria meningitidis; Type I Secretion Systems
PubMed: 28670572
DOI: 10.3389/fcimb.2017.00256 -
PLoS Pathogens Mar 2020It is increasingly being recognised that the interplay between commensal and pathogenic bacteria can dictate the outcome of infection. Consequently, there is a need to...
It is increasingly being recognised that the interplay between commensal and pathogenic bacteria can dictate the outcome of infection. Consequently, there is a need to understand how commensals interact with their human host and influence pathogen behaviour at epithelial surfaces. Neisseria meningitidis, a leading cause of sepsis and meningitis, exclusively colonises the human nasopharynx and shares this niche with several other Neisseria species, including the commensal Neisseria cinerea. Here, we demonstrate that during adhesion to human epithelial cells N. cinerea co-localises with molecules that are also recruited by the meningococcus, and show that, similar to N. meningitidis, N. cinerea forms dynamic microcolonies on the cell surface in a Type four pilus (Tfp) dependent manner. Finally, we demonstrate that N. cinerea colocalises with N. meningitidis on the epithelial cell surface, limits the size and motility of meningococcal microcolonies, and impairs the effective colonisation of epithelial cells by the pathogen. Our data establish that commensal Neisseria can mimic and affect the behaviour of a pathogen on epithelial cell surfaces.
Topics: A549 Cells; Bacterial Adhesion; Epithelial Cells; Fimbriae, Bacterial; Humans; Neisseria cinerea; Neisseria meningitidis
PubMed: 32208456
DOI: 10.1371/journal.ppat.1008372 -
Glycoconjugate Journal Aug 2021Neisseria meningitidis is a major cause of bacterial meningitidis worldwide. Children less than five years and adolescents are particularly affected. Nearly all invasive... (Review)
Review
Neisseria meningitidis is a major cause of bacterial meningitidis worldwide. Children less than five years and adolescents are particularly affected. Nearly all invasive strains are surrounded by a polysaccharide capsule, based on which, 12 N. meningitidis serogroups are differentiated. Six of them, A, B, C, W, X, and Y, cause the vast majority of infections in humans. Mono- and multi-valent carbohydrate-based vaccines against meningococcal infections have been licensed or are currently in clinical development. In this mini-review, an overview of the past and present approaches for producing meningococcal glycoconjugate vaccines is provided.
Topics: Glycoconjugates; Humans; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis; Vaccines, Conjugate
PubMed: 33905086
DOI: 10.1007/s10719-021-09990-y