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Bacterial populations as perfect gases: genomic integrity and diversification tensions in Helicobacter pylori

Key Points

  • The Gram-negative bacterium Helicobacter pylori is the predominant organism that colonizes the human stomach. In this article, the authors give their views on some of the genetic mechanisms that have allowed this organism to be so successful in this harsh environment.

  • The article focuses on the tensions between the opposing forces of maintaining genome integrity and increasing genome diversification in H. pylori. The stomach comprises various macroniches, which differ in anatomical location and therefore also in physiological properties. The authors propose that the tensions between integrity and diversification create a dynamic pool of genetic variants that is sufficiently genetically diverse to occupy many of the potential niches in the stomach. The authors draw an analogy with a perfect gas that can fill any volume.

  • The different mechanisms that H. pylori uses to generate its extraordinary diversity are reviewed, including diversity at the cellular level through inter-and intragenomic recombination, and diversity at the population level.

  • The mechanisms that control genome infidelity are then reviewed in detail. These include mismatch repair (absent from H. pylori), translesion synthesis, nucleotide excision repair, base excision repair and recombinational repair.

  • Finally, the role of restriction–modification systems in keeping the competing genotypes in balance is considered.

Abstract

Microorganisms that persist in single hosts face particular challenges. Helicobacter pylori, an obligate bacterial parasite of the human stomach, has evolved a lifestyle that features interstrain competition and intraspecies cooperation, both of which involve horizontal gene transfer. Microbial species must maintain genomic integrity, yet H. pylori has evolved a complex nonlinear system for diversification that exists in dynamic tension with the mechanisms for ensuring fidelity. Here, we review these tensions and propose that they create a dynamic pool of genetic variants that is sufficiently genetically diverse to allow H. pylori to occupy all of the potential niches in the stomach.

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Figure 1: Bacterial mechanisms to control DNA damage.
Figure 2: Tensions between genomic integrity and diversification in Helicobacter pylori.
Figure 3: A model of the role of microbial variation in niche colonization.

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Acknowledgements

This work was supported in part by the National Institutes of Health, the Senior Scholar Award in Infectious Diseases from the Ellison Medical Foundation, and the Diane Belfer Program for Human Microbial Ecology.

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Correspondence to Martin J. Blaser.

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The authors declare no competing financial interests.

Related links

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DATABASES

Entrez Genome Project

Aquifex aeolicus

Escherichia coli

H. pylori 26695

H. pylori J99

H. pylori HPAG1

Neisseria meningitidis

Thermotoga maritima

Wolinella succinogenes

FURTHER INFORMATION

H.pylori MLST database

Glossary

RAPD

(Random amplification of polymorphic DNA). A marker system that relies on the use of short PCR primers.

MLST

(Multilocus sequence typing). A method for the genotypic characterization of bacteria, using the allelic mismatches of a small number (usually seven) of housekeeping genes. Designed as a tool in molecular epidemiology and used for recognizing distinct strains within named species.

Synonymous

A nucleotide change that does not alter the amino acid that is encoded.

Chimerism

The quality of being a chimera. In genetics, a chimera refers to a gene mosaic, composed of distinct genetic sequences from two or more strains.

Restriction-modification (RM) system

A bacterial mechanism of defence against invasion by foreign DNA (for example, bacteriophage). Comprises genes that encode a restriction enzyme and a modification methylase.

Competence

The ability of bacteria to take up extracellular DNA.

Transformation

The uptake and incorporation of exogenous, 'naked' DNA directly from the environment.

Panmixis

Characterized by a lack of restriction in genetic exchange in a population; all individuals within the species population are potential recombination partners.

Linkage equilibrium

The situation when the association between two loci is random.

Homoplasy

An identical mutation or similar characteristic found in phylogenetically unrelated lineages. In bacteria, homoplasic mutations can be generated by either repeated, independent mutation or by recombination.

Slip-strand mispairing

Tandem direct repeats can pair incorrectly during DNA replication. For example, 'slippage' between the template and newly synthesized DNA strands during replication can result in pairing between, for example, the third repeat unit on the new strand and the fourth repeat on the template strand. Such mispairing results in a change in the number of repeats in the newly synthesized strand compared with the template DNA.

Quasispecies

Closely related, non-identical genomes subjected to ongoing mutation, recombination, competition and selection.

Mismatch repair

A process of DNA repair in which a mispaired region of a DNA duplex is excised and replaced by resynthesis using the remaining strand as a template.

Nucleotide excision repair

The replacement of nucleotides 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.

Base excision repair

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

Translesion synthesis

A type of specialized DNA synthesis, in which translesion polymerases can synthesize past lesions in the complementary strand that would normally block standard polymerases. Once the lesion is overcome, standard polymerases replace the less accurate translesion enzymes.

SOS response

The bacterial response to DNA damage. The SOS response is regulated by the LexA and RecA proteins and involves the expression of a network of >40 genes, including several DNA-repair enzymes.

Mutator phenotype

A bacterial strain with hyper-recombination is referred to as a mutator.

Second-order selection

Selection for organisms with mutator alleles, which have increased adaptive potential and genetic variability.

Holliday junction

An intermediate stage in genetic recombination that is formed when the strands of two double-stranded DNA molecules exchange partners.

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Kang, J., Blaser, M. Bacterial populations as perfect gases: genomic integrity and diversification tensions in Helicobacter pylori. Nat Rev Microbiol 4, 826–836 (2006). https://doi.org/10.1038/nrmicro1528

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