scholarly journals Histone H3 deacetylation promotes host cell viability for efficient infection by Listeria monocytogenes

2021 ◽  
Vol 17 (12) ◽  
pp. e1010173
Author(s):  
Matthew J. G. Eldridge ◽  
Mélanie A. Hamon
Keyword(s):  
Dna Damage ◽  
Listeria Monocytogenes ◽  
Cell Viability ◽  
Host Cell ◽  
Histone H3 ◽  
Bacterial Pathogen ◽  
Genome Integrity ◽  
Nucleic Acid Binding ◽  
Acid Binding Protein ◽  
Common Strategy

For many intracellular bacterial pathogens manipulating host cell survival is essential for maintaining their replicative niche, and is a common strategy used to promote infection. The bacterial pathogen Listeria monocytogenes is well known to hijack host machinery for its own benefit, such as targeting the host histone H3 for modification by SIRT2. However, by what means this modification benefits infection, as well as the molecular players involved, were unknown. Here we show that SIRT2 activity supports Listeria intracellular survival by maintaining genome integrity and host cell viability. This protective effect is dependent on H3K18 deacetylation, which safeguards the host genome by counteracting infection-induced DNA damage. Mechanistically, infection causes SIRT2 to interact with the nucleic acid binding protein TDP-43 and localise to genomic R-loops, where H3K18 deacetylation occurs. This work highlights novel functions of TDP-43 and R-loops during bacterial infection and identifies the mechanism through which L. monocytogenes co-opts SIRT2 to allow efficient infection.

scholarly journals Histone H3 deacetylation promotes host cell viability for efficient infection by Listeria monocytogenes

2021 ◽  
Author(s):  
Matthew J. G. Eldridge ◽  
Melanie A Hamon
Keyword(s):  
Dna Damage ◽  
Listeria Monocytogenes ◽  
Cell Viability ◽  
Host Cell ◽  
Histone H3 ◽  
Bacterial Pathogen ◽  
Genome Integrity ◽  
Nucleic Acid Binding ◽  
Acid Binding Protein ◽  
Common Strategy

For many intracellular bacterial pathogens manipulating host cell survival is essential for maintaining a replicative niche, and is a common strategy used to promote infection. The bacterial pathogen Listeria monocytogenes is well known to hijack host machinery for its own benefit, such as targeting the host histone H3 for modification by SIRT2. However, in what way this modification benefits infection, as well as the molecular players involved, remain unknown. Here we show that SIRT2 activity supports Listeria intracellular survival by maintaining genome integrity and host cell viability. This protective effect is dependent on H3K18 deacetylation, which safeguards the host genome by counteracting infection-induced DNA damage. Mechanistically, infection causes SIRT2 to interact with the nucleic acid binding protein TDP-43 and localise to genomic R-loops, where H3K18 deacetylation occurs. This work highlights novel functions of TDP-43 and R-loops during bacterial infection and identifies the mechanism through which L. monocytogenes co-opts SIRT2 to allow efficient infection.

scholarly journals Invasion of the Brain by Listeria monocytogenes Is Mediated by InlF and Host Cell Vimentin

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Pallab Ghosh ◽  
Elizabeth M. Halvorsen ◽  
Dustin A. Ammendolia ◽  
Nirit Mor-Vaknin ◽  
Mary X. D. O’Riordan ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Host Cell ◽  
Bacterial Pathogen ◽  
Surface Protein ◽  
Host Cells ◽  
Intermediate Filament Protein ◽  
Life Threatening ◽  
Host Cell Surface ◽  
Filament Protein ◽  
The Brain

ABSTRACTListeria monocytogenesis a facultative intracellular bacterial pathogen that is frequently associated with food-borne infection. Of particular concern is the ability ofL. monocytogenesto breach the blood-brain barrier, leading to life-threatening meningitis and encephalitis. The mechanisms used by bacterial pathogens to infect the brain are not fully understood. Here we show thatL. monocytogenesis able to utilize vimentin for invasion of host cells. Vimentin is a type III intermediate filament protein within the cytosol but is also expressed on the host cell surface. We found thatL. monocytogenesinteraction with surface-localized vimentin promoted bacterial uptake. Furthermore, in the absence of vimentin,L. monocytogenescolonization of the brain was severely compromised in mice. TheL. monocytogenesvirulence factor InlF was found to bind vimentin and was necessary for optimal bacterial colonization of the brain. These studies reveal a novel receptor-ligand interaction that enhances infection of the brain byL. monocytogenesand highlights the importance of surface vimentin in host-pathogen interactions.IMPORTANCEListeria monocytogenesis an intracellular bacterial pathogen that is capable of invading numerous host cells during infection.L. monocytogenescan cross the blood-brain barrier, leading to life-threatening meningitis. Here we show that anL. monocytogenessurface protein, InlF, is necessary for optimal colonization of the brain in mice. Furthermore, in the absence of vimentin, a cytosolic intermediate filament protein that is also present on the surface of brain endothelial cells, colonization of the brain was significantly impaired. We further show that InlF binds vimentin to mediate invasion of host cells. This work identifies InlF as a bacterial surface protein with specific relevance for infection of the brain and underscores the significance of host cell surface vimentin interactions in microbial pathogenesis.

scholarly journals Listeria monocytogenes Exploits Normal Host Cell Processes to Spread from Cell to Cell✪

1999 ◽  
Vol 146 (6) ◽  
pp. 1333-1350 ◽  
Author(s):  
Jennifer R. Robbins ◽  
Angela I. Barth ◽  
Hélène Marquis ◽  
Eugenio L. de Hostos ◽  
W. James Nelson ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Host Cell ◽  
Mdck Cells ◽  
Recipient Cell ◽  
Cell Monolayer ◽  
Bacterial Pathogen ◽  
Host Cells ◽  
Turnover Rates ◽  
Membrane Bound ◽  
Intercellular Spread

The bacterial pathogen, Listeria monocytogenes, grows in the cytoplasm of host cells and spreads intercellularly using a form of actin-based motility mediated by the bacterial protein ActA. Tightly adherent monolayers of MDCK cells that constitutively express GFP-actin were infected with L. monocytogenes, and intercellular spread of bacteria was observed by video microscopy. The probability of formation of membrane-bound protrusions containing bacteria decreased with host cell monolayer age and the establishment of extensive cell-cell contacts. After their extension into a recipient cell, intercellular membrane-bound protrusions underwent a period of bacterium-dependent fitful movement, followed by their collapse into a vacuole and rapid vacuolar lysis. Actin filaments in protrusions exhibited decreased turnover rates compared with bacterially associated cytoplasmic actin comet tails. Recovery of motility in the recipient cell required 1–2 bacterial generations. This delay may be explained by acid-dependent cleavage of ActA by the bacterial metalloprotease, Mpl. Importantly, we have observed that low levels of endocytosis of neighboring MDCK cell surface fragments occurs in the absence of bacteria, implying that intercellular spread of bacteria may exploit an endogenous process of paracytophagy.

scholarly journals The Tousled-Like Kinases as Guardians of Genome Integrity

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Arrigo De Benedetti
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Histone H3 ◽  
Chromatin Assembly ◽  
Genome Integrity ◽  
Cancer Management ◽  
Damage Response ◽  
Assembly Factor ◽  
Key Issues ◽  
Cell Cycle Signaling

The Tousled-like kinases (TLKs) function in processes of chromatin assembly, including replication, transcription, repair, and chromosome segregation. TLKs interact specifically (and phosphorylate) with the chromatin assembly factor Asf1, a histone H3-H4 chaperone, histone H3 itself at Ser10, and also Rad9, a key protein involved in DNA repair and cell cycle signaling following DNA damage. These interactions are believed to be responsible for the action of TLKs in double-stranded break repair and radioprotection and also in the propagation of the DNA damage response. Hence, I propose that TLKs play key roles in maintenance of genome integrity in many organisms of both kingdoms. In this paper, I highlight key issues of the known roles of these proteins, particularly in the context of DNA repair (IR and UV), their possible relevance to genome integrity and cancer development, and as possible targets for intervention in cancer management.

scholarly journals Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA inListeria

2016 ◽  
Vol 113 (51) ◽  
pp. 14733-14738 ◽  
Author(s):  
Michael Hall ◽  
Christin Grundström ◽  
Afshan Begum ◽  
Mikael J. Lindberg ◽  
Uwe H. Sauer ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Listeria Monocytogenes ◽  
Host Cell ◽  
Regulatory Protein ◽  
Bacterial Pathogen ◽  
Dna Interaction ◽  
Structural Basis ◽  
Published Data ◽  
Transcriptional Activators ◽  
Regulatory Factor

Infection by the human bacterial pathogenListeria monocytogenesis mainly controlled by the positive regulatory factor A (PrfA), a member of the Crp/Fnr family of transcriptional activators. Published data suggest that PrfA requires the binding of a cofactor for full activity, and it was recently proposed that glutathione (GSH) could fulfill this function. Here we report the crystal structures of PrfA in complex with GSH and in complex with GSH and its cognate DNA, thehlyoperator PrfA box motif. These structures reveal the structural basis for a GSH-mediated allosteric mode of activation of PrfA in the cytosol of the host cell. The crystal structure of PrfAWTin complex only with DNA confirms that PrfAWTcan adopt a DNA binding-compatible structure without binding the GSH activator molecule. By binding to PrfA in the cytosol of the host cell, GSH induces the correct fold of the HTH motifs, thus priming the PrfA protein for DNA interaction.

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