Neisseria meningitidis

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Neisseria meningitidis
Scientific classification
Kingdom: Bacteria Phylum: Proteobacteria Class: Beta Proteobacteria Order: Neisseriales Family: Neisseriaceae Genus: Neisseria Species: meningitidis
Binomial name
Neisseria meningitidis

Description & Significance

Neisseria meningitidis is a type of gram negative, parasitic, aerobic bacteria included among the proteobacteria. These organisms are extremely oxidase and catalase positive, are nonmotile or endospore forming and are extremely susceptible to drying. N. meningitidis bacteria are also diplococci, and therefore resemble coffee beans somewhat in their shape.

This bacteria has been found to be the causative agent of bacterial meningitis, a disease that has appeared to date back to the 16th century. However, the disease was only first described in 1805 by Swiss physician Gaspard Vieusseaux(11). Following Vieusseaux, Italian pathologists Ettore Marchiafava and Angelo Celli also described the micrococci in a sample of cerebral spinal fluid (CSF). Finally in 1887, the bacteria was isolated by Anton Weichselbaum(12).

Genome

The genome of Neisseria menignitidis, as well as other bacteria, contains its DNA within which its entire hereditary information is encoded. The genome of 3 of the 13 serotypes have been sequenced. Strain Z2491, belonging to serotype A, was completely sequenced in September of 2001 by the Sanger Institute. The genome of this particular strain was found to be circular, with a nucleotide length of 2,184,406, was found to contain 2,208 genes, 2,049 protein coding genes, 72 structural RNAs, 87 pseudogenes, 1 contig, be 80% coding and have a GC content of 51% (4).

Strain MC58 (serotype B) was sequenced by the TIGR Center in September of 2001. It's genome was found to be circular, 2,272,360 nucleotides in length, as well as 79% coding and have a GC content of 51%. Furthermore it was found to contain 2,225 genes, 2,063 protein coding genes, 71 structural RNAs, 91 pseudogenes and no contigs (5).

Sequencing of strain FAM18 (serotype C) was completed by the Sanger Institute in January of 2004 as well and it's genome was also found to be circular. It was 2,194,961 nucleotides in length, had 2,046 genes, 1,917 protein coding genes, 71 structural RNAs, 58 pseudogenes, no contigs, be 81% coding and have a GC content of 51% (6).

Clearly, the information provided by the genomic sequencing of strains Z2491, MC58 and FAM18 of serotypes A, B, and C, respectively, has enabled researches to discover the means by which this bacteria invade and infect their hosts. Furthermore, without this molecular level understanding, vaccination and treatment are not only made possible, but more efficient as well.

Cell structure and metabolism

A notable feature of this bacteria are it's prominent antiphagocytic polysaccharide capsules. The 13 known serogroups; A, B, C, H, I, K, L, M, X, Y, Z, 29E and W135; are grouped on the basis of the capsular polysaccharides which envelope them. They are then further classified into 10 serotypes on the basis of class 2 or 3 OMP antigens, as well as 10 subtypes on the basis of class 1 OMP antigens, and finally 13 immunotypes on the basis of lipooligosccharide antigens. The cell surface of Neisseria meningitidis also possesses type IV pili, which are retractile fibers that serve in their attachment to epithelial cells during host colonization and invasion. N. meningitidis also contains an outer membrane integral protein known as OpcA. This protein's purpose has been linked to cell adhesion of Neisseria meningitidis to epithelial, as well as endothelial cells via binding to vitronectin and proteoglycan cell-surface receptors located within the host. The OpcA protein has been found to function independently of pilus based adhesion (8), mentioned above.

As far as the bacteria's metabolism is concerned, a study conducted by Archibald and Devoe have provided insight into the dependency for N. meningitidis to metabolize iron in order to maintain cellular functioning (1). Other studies of the bacteria appear to point to the necessity for the obtainment of glucose, pyruvate, or lactate as a sole carbon source as well (2). Further detail on the later of these two studies can be found below, under Current Research.

Ecology

Neisseria meningitidis is strictly found in human hosts- no animal hosts are known to exist. Due to the fact that iron reduction is key to N.meningitidis' survival and flourishment, heme iron found in human blood provides the perfect breeding ground for this bacteria. However, Neisseria meningitidis impose no detrimental affects on their hosts as long as they remain in the nasopharyngeal tract. N. meningitidis provide no direct benefits to their human hosts either.

Pathology

As mentioned earlier, there are approximately 13 serogroups of Neisseria meningiditis. The genes of the sequenced serogroups have been found to undergo phase variation more so than any other pathogen studied to date. Accordingly, this ability seems to underlie the bacteria's expression and contributes to their ability to persevere over the hosts immune system response. Among these known strains, serogroups A, B, and C have been found to be those responsible for 90% of meningococcal meningitis and septicemia cases. Specifically, serogroup A has been implicated in meningitis epidemics in developing countries, while serogroups B and C have been implicated in meningitis epidemics in already developed countries.

Neisseria meningitidis is only found in human hosts of which 5-15% of the population are carriers. There is a 3-30% normal carrier state lasting days to months that provides the reservoir for infection of susceptible persons. Specifically, the bacterium can be found in the nasopharyngeal tract, in its asymptomatic form. Transformation from it's initial asymptomatic form into meningitis arises when the bacterium crosses the mucosal barrier via type IV pili, and enters the blood stream. Once in the blood stream they are free to travel to the cerebral spinal fluid or the meninges, tissues that surround the brain and spinal cord. Accordingly, this infection of the meninges results in bacterial meningitis.

Meningitis results in the swelling of the meninges and causes flu-like such as high fever, severe headache, and neck stiffness and pain that make touching your chin to your chest difficult. It is also highly contagious, easily passed to individuals via kissing, sexual contact, coughing and sneezing, giving birth and living in crowded conditions such as dormitories. Risk factors for contracting this disease include time of year (most prevalent during late winter/early spring) being male, age, genetics, a weakened immune system due to a condition such as HIV, and living in crowded conditions as for mentioned. If left untreated meningitis could result in meningococcal septicemia and/or death. Fortunately, antibiotics and steroid medications can be used to cure the disease and treat inflammation, respectively (10).

Application to Biotechnology

Research conducted on the various serotypes and strains of Neisseria meningitidis have yeilded no beneficial enzymes or compounds that are applicable to biotechnology.

Current Research

Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes.

As stated earlier serogroups A, B and C of Neisseria meningitidis are the leading causes of bacterial meningitis. Specifically, of these serogroups, MenB is not only the leading cause of the majority of meningitis cases that develop, but is the only one of the three serogroups that there has yet to be a vaccine developed for.

Taking into account that vaccinations for the other strains were attained via polysaccharide vaccines, current researchers have set out to develop and effective vaccine for serogoup B using outer membrane protein- and lipopolysaccharide- based approaches as well as "reverse vaccinology" in which systematic search of the bacteria's genome is performed in order to attain the identity of novel proteins. Furthermore, this technique has enabled researchers to improve their ability to develop better vaccines by "increasing the speed of target identification."

The research performed in this article used genome scale constraint-based metabolic models to analyze culture data, obtain a better understanding of cellular metabolism and develop metabolic engineering strategies for serogroup B Neisseria meningitidis. With the use of a genomic database for this particular serogroup, the main primary metabolic pathways were selected. These pathways included Entner-Douderoff and pentose phosphate pathways as well as the tricarboylic acid cycle. With an understanding of the means by which these pathways operate metabolite concentration (e.g. glucose and lactate), protein composition, and the amount of fatty acids and lipopolysaccharides, among other biochemical and physiological data, were assessed.

Using the genomic database of Neisseria meningitidis serogroup B along with the biochemical and physiological data obtained, a "genome-scale flux model for vaccine process development purposes was constructed."

Meningococcal biofilm formation: structure, development and phenotypes in a standardized continuous flow system

This study used a standardized in vitro flow system in order to demonstrate that non-capsulated strains of Neisseria meningitids formed biofilms in which bacteria aggregate together. This action results in the production of an adhesive matrix that permits surface attachment (e.g. to a host). Within a number of the experimental colonies microcolonies formed.

In regards to strain MC58 (serogroup B) this production was believed to occur if a functional copy of the pilE gene was present. This gene is responsible for the coding of pilin, which in it's presence, causes cells to twitch. However, "unpiliated pilE mutants formed biofilms," which negated the belief that microcolony formation and adhesion depended upon pilis expression.

Furthermore, PilX, a type IV pilus-associated protein was revealed to play an essential role in the formation of aggregates similar to those occurring among erythrocytes (red blood cells.) And while researchers have identified a number of alleles responsible for PilX expression, each seemed to "differ in their propensity to support autoaggregation of cells in suspension, but not in their ability to support microcolony formation within biofilms in the continuous flow system.

Role of Neisseria meningitidis luxS in Cell-to-Cell Signaling and Bacteremic Infection

A vast amount of research is being performed on Neisseria meningitidis in order to gain further insight into a varitey of different areas. In this study, researchers have used serogroup B Neisseria meningitidis as a means of ascertaining the effect that luxS has on the bacteria's virulence. LuxS is required for autoindicer-2 (AI-2) production. Autoinducer-2 is a boron-based molecule that is produced by bacteria, such as N. meninigitidis, that controls the signals in the quorum sensing process by which biofilms establish a network of communication between them. Numerous bacteria have been found to posses luxS. In this particular study researchers have discovered that serotype B Neisseria meningitidis posses a functional copy of luxS that is vital for full meningococcal virulence. Consequently, strains that lack luxS (due to a deletion) are defective to bacteremia, a precursor of meningococcal pathogenesis.

The data obtained in this article alludes to the possibility that not only does LuxS seem to account for the virulence of MenB, but also poses the idea that inhibiting the LuxS pathway itself may serve as a preventative means by which to keep meningitis from occurring.

References

1. Archbald, Frederick S. and I.W. DeVoe. "Iron in Neisseria meningitidis: Minimum Requirements, Effects[ of Limitation, and Characteristics of Uptake." Journal or Bacteriology OCT 1978 35-48. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=218629

2. Baart, Gino JE, Bert Zomer, Alex de Haan, Leo A van der Pol, E Coen Beuvery, Johannes Tramper and Dirk E Martens. "Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes." Genome Biology 2007, 8:R136. http://genomebiology.com/2007/8/7/R136

3. Lappann, Marin, Janus A.J. Haagensen, Heike Claus, Ulrich Vogel, Søren Molin. “Meningococcal biofilm formation: structure, development, and phenotypes in a standardized continuous flow system.” Molecular Microbiology 13 OCT 2006. 62 (5) 1292-1309 http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2958.2006.05448.x

4. NCBI Entrez Genome Sequence. “Neisseria meningitidis Z2491 complete genome.” http://www.ncbi.nlm.nih.gov/sites/entrez?Db=Genome&Cmd=ShowDetailView&TermToSearch=156

5. NCBI Entrez Genome Sequence. “Neisseria meningitidis MC58 complete genome.” http://www.ncbi.nlm.nih.gov/sites/entrez?Db=Genome&Cmd=ShowDetailView&TermToSearch=155

6. NCBI Entrez Genome Sequence. “Neisseria meningitidis FAM18 complete genome.” http://www.ncbi.nlm.nih.gov/sites/entrez?Db=Genome&Cmd=ShowDetailView&TermToSearch=20258

[1] <Neisseria meningitidis." Wikipedia the Free Encyclopedia 13 APR 2008. http://en.wikipedia.org/wiki/Neisseria_meningitidis

8. Prince, Stephen M, Achtman, Mark, and Derrick, Jeremy P. "Crystal structure of the OpcA integral membrane adhesin from Neisseria meningitidis." Proc Natl Acad Sci U S A. 2002 March 19; 99(6): 3417–3421. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=122538

9. Sanger Insitute. "Neisseria meningitidis." 21 May 2004. http://www.sanger.ac.uk/Projects/N_meningitidis

10. Web MD. "Meningitis." Healthwise Inc. 19 Jan 2007. http://www.webmd.com/a-to-z-guides/meningitis-cause

11. Weichselbaum A: Ueber die aetiologie der akuten meningitis cerebrospinalis. Fortscher Med 1887; 5:573-583

12. Vieusseaux M: Mémoire sur le maladie qui a regne a Génève au printemps de 1805. Journal de Médecine, Chimie, et Pharmacologie 1805. 11;163