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When our genome is targeted by pathogenic bacteria

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Abstract

Eukaryotic cells repair thousands of lesions arising in the genome at each cell cycle. The most hazardous damage is likely DNA double-strand breaks (DSB) that cleave the double helix backbone. DSBs occur naturally during T cell receptor and immunoglobulin gene recombination in lymphocytes. DSBs can also arise as a consequence of exogenous stresses (e.g., ionizing irradiation, chemotherapeutic drugs, viruses) or oxidative processes. An increasing number of studies have reported that infection with pathogenic bacteria also alters the host genome, producing DSB and other modifications on DNA. This review focuses on recent data on bacteria-induced DNA damage and the known strategies used by these pathogens to maintain a physiological niche in the host. Even after DNA repair in infected cells, “scars” often remain on chromosomes and might generate genomic instability at the next cell division. Chronic inflammation in tissue, combined with infection and DNA damage, can give rise to genomic instability and eventually cancer. A functional link between the DNA damage response and the innate immune response has been recently established. Pathogenic bacteria also highjack the host cell cycle, often acting on the stability of the master regulator p53, or dampen the DNA damage response to support bacterial replication in an appropriate reservoir. Except in a few cases, the molecular mechanisms responsible for DNA lesions are poorly understood, although ROS release during infection is a serious candidate for generating DNA breaks. Thus, chronic or repetitive infections with genotoxic bacteria represent a common source of DNA lesions that compromise host genome integrity.

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Abbreviations

ATM:

Ataxia telangiectasia mutated

ATR:

Ataxia telangiectasia and Rad3-related

53BP1:

p53 binding protein 1

Chk1/2:

Checkpoint kinase 1/2

DNA-PK:

DNA protein kinase

dsDNA:

Double-stranded DNA

CDT:

Cytolethal distending toxin

DDR:

DNA damage response

DSB/SSB:

Double/Single strand breaks

HR:

Homologous recombination

IRIF:

Ionizing radiation induced foci

LLO:

Lysteriolysin O

MCD1:

Mediator of DNA-damage checkpoint 1

M/HDM2:

Mouse/Human double minute 2 homolog

MNR:

Mre11, Nbs1 and Rad50

MOI:

Multiplicity of infection

Mre11:

Mediator of DNA damage checkpoint

NHEJ:

Non-Homologous End Joining

OGG1:

8-oxoguanine DNA glycosylase

PARP:

Poly(ADP-ribose) polymerase

PRR:

Pattern recognition receptor

PI3KK:

Phosphatidylinositol 3-kinase-like kinase

ROS:

Reactive oxygen and nitrogen species

STING:

Stimulator of interferon genes

TTSS:

Type III secretion system

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Acknowledgments

CL thanks Dr. Joël Gaffé (Adaptation and Pathogeny of Micro-organisms Laboratory, University Grenoble Alpes, CNRS) for critical reading and comments on the manuscript, Dr. Sandeep Nadendla for his careful reading and help with English language.

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  1. INSERM, UMR_S 1038, BGE (Large Scale Biology), 38054, Grenoble, France

    Claudie Lemercier

  2. CEA, iRTSV, BGE, 38054, Grenoble, France

    Claudie Lemercier

  3. Université Grenoble-Alpes, 38000, Grenoble, France

    Claudie Lemercier

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Lemercier, C. When our genome is targeted by pathogenic bacteria. Cell. Mol. Life Sci. 72, 2665–2676 (2015). https://doi.org/10.1007/s00018-015-1900-8

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