Listeria monocytogenes induces host DNA damage and delays the host cell cycle to promote infection.
Cell Cycle
; 13(6): 928-40, 2014.
Article
in En
| MEDLINE
| ID: mdl-24552813
ABSTRACT
Listeria monocytogenes (Lm) is a human intracellular pathogen widely used to uncover the mechanisms evolved by pathogens to establish infection. However, its capacity to perturb the host cell cycle was never reported. We show that Lm infection affects the host cell cycle progression, increasing its overall duration but allowing consecutive rounds of division. A complete Lm infectious cycle induces a S-phase delay accompanied by a slower rate of DNA synthesis and increased levels of host DNA strand breaks. Additionally, DNA damage/replication checkpoint responses are triggered in an Lm dose-dependent manner through the phosphorylation of DNA-PK, H2A.X, and CDC25A and independently from ATM/ATR. While host DNA damage induced exogenously favors Lm dissemination, the override of checkpoint pathways limits infection. We propose that host DNA replication disturbed by Lm infection culminates in DNA strand breaks, triggering DNA damage/replication responses, and ensuring a cell cycle delay that favors Lm propagation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Damage
/
Cell Cycle
/
Host-Pathogen Interactions
/
Listeriosis
/
Listeria monocytogenes
Limits:
Humans
Language:
En
Journal:
Cell Cycle
Year:
2014
Document type:
Article
Affiliation country:
Portugal