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Meningococcal genome dynamics

Nature Reviews Microbiology volume 4, pages 11–22 (2006)Cite this article

Key Points

  • Neisseria meningitidis (the meningococcus) is an important commensal, pathogen and model organism with a small but hyperdynamic genome.

  • Meningococcal fitness, genome evolution and diversity result from a fine-tuned balance between mechanisms for variability and maintenance.

  • DNA-repair mechanisms probably have a key role in genome dynamics in the meningococcus.

  • Neisserial mutY mutants show high spontaneous mutation rates, and the meningococcal DNA glycosylase MutY has a prominent role in DNA repair.

  • Unique features of meningococcal DNA repair include the relative importance of MutY in synergy with Fpg, and the lesser influence of MutS in the prevention of spontaneous DNA damage.

  • Meningococcal DNA-uptake sequences required for transformation show a biased distribution towards genome-maintenance genes, ensuring their prioritized uptake through transformation if irreparably damaged or lost.

  • Instead of sensing the environment and responding accordingly, meningococcal cells seem to generate a surplus of genetic variants, on which selective pressures can act.

  • Horizontal gene transfer and DNA recombination are key processes that result in genome diversity in the meningococcus. Further analysis of these processes will enhance our understanding of genome dynamics.

  • Chromosomal alterations and polymorphisms ensuing from genome instability provide the meningococcus with adaptability and ensure immune evasion. These mechanisms also represent immense challenges for vaccine development and combating drug resistance.

Abstract

Neisseria meningitidis (the meningococcus) is an important commensal, pathogen and model organism that faces up to the environment in its exclusive human host with a small but hyperdynamic genome. Compared with Escherichia coli, several DNA-repair genes are absent in N. meningitidis, whereas the gene products of others interact differently. Instead of responding to external stimuli, the meningococcus spontaneously produces a plethora of genetic variants. The frequent genomic alterations and polymorphisms have profound consequences for the interaction of this microorganism with its host, impacting structural and antigenic changes in crucial surface components that are relevant for adherence and invasion as well as antibiotic resistance and vaccine development.

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Figure 1: Genetic diversity, genetic instability and fitness of the meningococcus.
Figure 2: Major DNA-repair pathways in Escherichia coli and the meningococcus.
Figure 3: Spontaneous mutagenicity of DNA-repair-deficient meningococci and Escherichia coli strains.
Figure 4: Mechanisms of meningococcal phase variation.
Figure 5: Antigenic variation.
Figure 6: Horizontal gene transfer by transformation of exogenous DNA.

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Acknowledgements

We deeply appreciate the discussions with the late Erling Seeberg on mechanisms of DNA repair. We thank O.H. Ambur and I. Alseth for critical reading of the manuscript.

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Authors and Affiliations

  1. Centre for Molecular Biology and Neuroscience and Institute of Microbiology, University of Oslo, Rikshospitalet, N-0027, Oslo, Norway

    Tonje Davidsen & Tone Tønjum

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  1. Tonje Davidsen
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Correspondence to Tone Tønjum.

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DATABASES

Entrez

Bacillus subtilis

Escherichia coli

Haemophilus influenzae

Helicobacter pylori

Mycobacterium tuberculosis

Neisseria gonorrhoeae

Neisseria meningitidis

Pseudomonas aeruginosa

Salmonella enterica serovar typhimurium

Streptococcus pneumoniae

FURTHER INFORMATION

Tone Tønjum's research homepages

Tone Tønjum's research homepages

Neisseria gonorrhoeae strain FA 1090 genome

Neisseria meningitidis serogroup C strain FAM18 genome

Glossary

Meningitis

Inflammation of the membranes (meninges) surrounding the brain.

Salpingitis

Inflammation of the fallopian tubes.

Recombination

The process by which parts, or all, of DNA molecules from two separate sources are exchanged or brought together into a single unit.

Oxidative burst

The release of reactive oxygen species by specialized immune cells of humans.

DNA uptake sequences

(DUS). Small repeated sequences that are required for DNA binding or uptake in natural transformation in members of the genus Neisseria.

Excision repair

A process for repairing altered bases, mismatches or small loops in DNA, in which a single-stranded section containing the aberrant structure is removed and the resulting gap is filled by DNA replication that is templated from the complementary strand.

Base excision repair

(BER). The excision and repair of bases that have been altered by small chemical modifications.

Mismatch repair

(MMR). An excision-repair pathway that identifies and corrects mispaired bases and 1–3-nucleotide loops.

Nucleotide excision repair

(NER). The replacement of DNA bases that are altered by large chemical additions or crosslinks through the excision of a short, single-stranded segment containing the damage.

Recombinational repair

A repair process that uses recombination enzymes to remove a DNA lesion and repair the patch by strand exchange.

DNA glycosylase

An enzyme involved in base excision repair that hydrolyses the N-glycosylic bond to release the altered base from the sugar–phosphate backbone, leaving an abasic site.

8oxoG system

A DNA-repair system dedicated to the removal of the oxidized form of guanine, 8oxoG. Composed of a triplet of enzymes — MutY, MutM (Fpg) and MutT.

Mutator

A bacterial strain showing an elevated mutation rate.

Phase variation

A molecular mechanism leading to a switching of the gene expression state, for example, on–off expression. Mediated by tandem repeats within the promoter region or the open reading frame.

SOS response

An inducible response allowing bacteria to circumvent the presence of abundant DNA damage by activating several DNA-repair genes as well as translesion DNA polymerases that are under the control of the LexA protein.

Antigenic variation

A molecular mechanism leading to a change in the antigenic expression state of surface components so that pre-existing host antibodies no longer recognize the component (immune evasion).

σ factor

A subunit of the RNA polymerase that dictates which promoters are being transcribed.

Two-component regulatory systems

System that responds to an environmental stimulus and regulates gene expression accordingly. Composed of a histidine-kinase sensor, usually situated in the outer membrane, that phosphorylates a response regulator in the cytoplasm which in turn activates transcription from selected promoters.

Global regulatory component

A component with a 'genome-wide' regulatory function.

Regulatory response elements

Elements that respond to a change in the environment and subsequently regulate gene expression, for example, σfactors, two-component regulatory systems and specific or global regulatory proteins.

Insertion sequences

A mobile stretch of DNA that can insertionally disrupt, and thereby inactivate, genes.

Natural transformation

Binding and uptake of free DNA, which is subsequently integrated into the genome by recombination.

Correia elements

Small insertion elements of 100–150 bp that are flanked by long terminal repeats.

Neisserial intergenic mosaic elements

(NIMEs). Repeat units of ∼50–150 bp, each flanked by 20-bp inverted repeats.

Homopolymeric tract

Several identical copies of single, di- tri- or tetranucleotides.

Gene conversion

A non-reciprocal transfer of genetic information.

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Davidsen, T., Tønjum, T. Meningococcal genome dynamics. Nat Rev Microbiol 4, 11–22 (2006). https://doi.org/10.1038/nrmicro1324

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