A Role for SIRT2-Dependent Histone H3K18 Deacetylation in Bacterial Infection

Eskandarian, Haig A.; Impens, Francis; Nahori, Marie–Anne; Soubigou, Guillaume; Coppée, Jean‐Yves; Cossart, Pascale; Hamon, Mélanie

doi:10.1126/science.1238858

Cited by 227 publications

(214 citation statements)

References 62 publications

(72 reference statements)

Supporting

Mentioning

204

Contrasting

Unclassified

Order By: Relevance

“…Perturbing the balance between these modifications leads to changes in gene expression (2). Recent publications provide evidence for the effect of histone modifications on regulation of the innate immune response and expression of associated defense genes (3,4).…”

mentioning

confidence: 99%

Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge

Fischer

Scotet

Friedman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Antimicrobial peptides (AMP) are defense effectors of the innate immunity playing a crucial role in the intestinal homeostasis with commensals and protection against pathogens. Herein we aimed to investigate AMP gene regulation by deciphering specific characteristics allowing their enhanced expression among innate immune genes, particularly those encoding proinflammatory mediators. Our emphasis was on epigenetic regulation of the gene encoding the AMP β-defensin 2 (HBD2), taken as a model of possibly specific induction, upon challenge with a commensal bacterium, compared with the proinflammatory cytokine IL-8. Using an in vitro model of colonic epithelial cells challenged with Escherichia coli K12, we showed that inhibition of histone deacetylases (HDAC) by trichostatin A dramatically enhanced induction of HBD2 expression, without affecting expression of IL-8. This mechanism was supported by an increased phosphorylation of histone H3 on serine S10, preferentially at the HBD2 promoter. This process occurred through activation of the IκB kinase complex, which also led to activation of NF-κB. Moreover, we demonstrated that NF-κB was modified by acetylation upon HDAC inhibition, partly by the histone acetyltransferase p300, and that both NF-κB and p300 supported enhanced induction of HBD2 expression. Furthermore, we identified additional genes belonging to antimicrobial defense and epithelial restitution pathways that showed a similar pattern of epigenetic control. Finally, we confirmed our finding in human colonic primary cells using an ex vivo organoid model. This work opens the way to use epigenetic pharmacology to achieve induction of epithelial antimicrobial defenses, while limiting the deleterious risk of an inflammatory response.

show abstract

mentioning

confidence: 99%

Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge

Fischer

Scotet

Friedman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Other genome alterations have been reported following L. monocytogenes infection. Indeed, this bacterium acts on host chromatin through histone deacetylation by Sirtuin 2 deacetylase, resulting in the repression of a set of genes [67]. Thus L. monocytogenes manipulates the eukaryotic genome through multiple mechanisms to promote the survival and replication of this bacterium.…”

Section: Strains Of Shigella Neisseria Listeria and Chlamydia Are Amentioning

confidence: 99%

When our genome is targeted by pathogenic bacteria

Lemercier

2015

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

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.

show abstract

“…SIRT2 is also present in the nucleus in the G2/M cell cycle transition and targets nuclear proteins such as p53. In addition, Sirt2 -/-mice can control listeriosis more efficiently than wild-type mice [99]. Therefore, the study of L. monocytogenes unveiled an additional nuclear function for SIRT2 in deacetylating histone H3 specifically on lysine 18, a process which is actively exploited by the bacteria to promote its survival.…”

Section: Monocytogenes Was One Of the First Reported Examples Of Amentioning

confidence: 99%

“…The L. monocytogenes poreforming toxin LLO triggers dephosphorylation of histone H3 on serine 10 and deacetylation of histone H4 [98]. In addition, upon binding to its receptor Met, internalin InlB induces the translocation of the host histone deacetylase sirtuin 2 (SIRT2) from the cytoplasm to the chromatin, where it deacetylates histone H3 on lysine 18, leading to modifications of the host cell transcriptome [99]. So far, SIRT2 was considered to only regulate in the cytoplasm microtubule dynamics through deacetylation of alpha-tubulin and NF-kB gene expression through deacetylation of p65 and also controls adipocyte differenciation and autophagy through deacetylation FOXO1 (for review, [100]).…”

Section: Monocytogenes Was One Of the First Reported Examples Of Amentioning

confidence: 99%

How the Study of Listeria Monocytogenes has Led to New Concepts in Biology

Rolhion

Cossart

2017

Future Microbiol.

Self Cite

View full text Add to dashboard Cite

The opportunistic intracellular bacterial pathogen Listeria monocytogenes has in 30 years emerged as an exceptional bacterial model system in infection biology. Research on this bacterium has provided considerable insight into how pathogenic bacteria adapt to mammalian hosts, invade eukaryotic cells, move intracellularly, interfere with host cell functions and disseminate within tissues. It also contributed to unveil features of normal host cells pathways and unsuspected functions of previously known cellular proteins. This review provides an updated overview of our knowledge on this pathogen. In many examples, findings on Listeria monocytogenes provided the basis for new concepts in bacterial regulation, cell biology and infection processes.

show abstract

A Role for SIRT2-Dependent Histone H3K18 Deacetylation in Bacterial Infection

Cited by 227 publications

References 62 publications

Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge

Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge

When our genome is targeted by pathogenic bacteria

How the Study of Listeria Monocytogenes has Led to New Concepts in Biology

Contact Info

Product

Resources

About