Listeria monocytogenes Dampens the DNA Damage Response

Samba-Louaka, Ascel; Pereira, Jorge A.; Nahori, Marie–Anne; Villiers, Véronique; Deriano, Ludovic; Hamon, Mélanie; Cossart, Pascale

doi:10.1371/journal.ppat.1004470

Cited by 40 publications

(37 citation statements)

References 43 publications

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“…It allows Listeria to selectively control the transcription of a subset of host genes, such as ISGs, independently from other nuclear functions affected by infection, such as the DNA damage response described in other studies [82,83].…”

Section: Discussionmentioning

confidence: 99%

Organelle targeting during bacterial infection: insights from Listeria

Lebreton

Stavru

Cossart

2015

Trends in Cell Biology

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Listeria monocytogenes, a facultative intracellular bacterium responsible for severe foodborne infections, is now recognized as a multifaceted model in infection biology. Comprehensive studies of the molecular and cellular basis of the infection have unraveled how the bacterium crosses the intestinal and feto-placental barriers, invades several cell types in which it multiplies and moves, and spreads from cell to cell. Interestingly, although Listeria does not actively invade host cell organelles, it can interfere with their function. We discuss the effect of Listeria on the endoplasmic reticulum (ER) and the mechanisms leading to the fragmentation of the mitochondrial network and its consequences, and review the strategies used by Listeria to subvert nuclear functions, more precisely to control host gene expression at the chromatin level.

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Section: Discussionmentioning

confidence: 99%

Organelle targeting during bacterial infection: insights from Listeria

Lebreton

Stavru

Cossart

2015

Trends in Cell Biology

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“…Although this bacterium induces DNA breaks in vitro and in vivo, researchers have shown that this invasive bacterium elicits unexpectedly low DDR via the activity of the LLO toxin. L. monocytogenes mutants lacking LLO induce a much higher DDR, whereas bacteria overexpressing the LLO toxin trigger lower DDR than wild-type bacteria [65]. Surprisingly, the pretreatment of cells with purified LLO inhibits DDR induced with extremely powerful genotoxic agents, such as gamma-irradiation and etoposide.…”

Section: Strains Of Shigella Neisseria Listeria and Chlamydia Are Amentioning

confidence: 99%

“…It has been shown that L. monocytogenes induces DSBs and γ H2AX at very low MOI (less than 1 bacterium per cell) [64]. This process is independent on the toxin lysteriolysin O (LLO), a pore-forming toxin with cytolytic activity localized at the plasma membrane [64], and bacterial internalization is not necessary for inducing host cell DNA damage [65]. Infection with L. monocytogenes increases host cell cycle duration without compromising cell viability and infected cells continue division to generate two infected cells [64].…”

Section: Strains Of Shigella Neisseria Listeria and Chlamydia Are Amentioning

confidence: 99%

“…A recent study conducted at the Pasteur Institute provided an additional piece of information on the complex mechanism used by L. monocytogenes to control the host DDR [65]. Although this bacterium induces DNA breaks in vitro and in vivo, researchers have shown that this invasive bacterium elicits unexpectedly low DDR via the activity of the LLO toxin.…”

Section: Strains Of Shigella Neisseria Listeria and Chlamydia Are Amentioning

confidence: 99%

“…Without the Mre11 sensor, DDR is impaired. The targeted reduction of several components of the DDR (including ATM, 53BP1 and H2AX, along with Mre11) substantially promotes L. monocytogenes replication, indicating that the host DDR acts as a negative regulator of infection [65]. The events downstream LLO leading to Mre11 degradation and DDR dampening are only beginning to emerge.…”

Section: Strains Of Shigella Neisseria Listeria and Chlamydia Are Amentioning

confidence: 99%

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When our genome is targeted by pathogenic bacteria

Lemercier

2015

Cell. Mol. Life Sci.

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Eukaryotic cells repair thousands of lesions arising in the genome at each cell cycle. The most hazardous damage is likely DNA doublestrand 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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Role of proapoptotic BH3‐only proteins in Listeria monocytogenes infection

et al. 2016

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The ability of pathogens to influence host cell survival is a crucial virulence factor. Listeria monocytogenes (Lm) infection is known to be associated with severe apoptosis of hepatocytes and spleen cells. This impairs host defense mechanisms and thereby facilitates the spread of intracellular pathogens. The general mechanisms of apoptosis elicited by Lm infection are understood, however, the roles of BH3-only proteins during primary Lm infection have not been examined. To explore the roles of BH3-only proteins in Lminduced apoptosis, we studied Listeria infections in mice deficient in Bim, Bid, Noxa or double deficient in BimBid or BimNoxa. We found that BimNoxa double knockout mice were highly resistant to high-dose challenge with Listeria. Decreased bacterial burden and decreased host cell apoptosis were found in the spleens of these mice. The ability of the BH3-deficient mice to clear bacterial infection more efficiently than WT was correlated with increased concentrations of ROS, neutrophil extracellular DNA trap release and downregulation of TNF-α. Our data show a novel pathway of infection-induced apoptosis that enhances our understanding of the mechanism by which BH3-only proteins control apoptotic host cell death during Listeria infection.Keywords: Apoptosis r Cytokines r Host-pathogens interactions r Immune evasion r TNF r Transgenic models Additional supporting information may be found in the online version of this article at the publisher's web-site

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Listeria monocytogenes Dampens the DNA Damage Response

Cited by 40 publications

References 43 publications

Organelle targeting during bacterial infection: insights from Listeria

Organelle targeting during bacterial infection: insights from Listeria

When our genome is targeted by pathogenic bacteria

Role of proapoptotic BH3‐only proteins in Listeria monocytogenes infection

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