TY  - JOUR
A1  - Sunkavalli, Ushasree
A1  - Aguilar, Carmen
A1  - Silva, Ricardo Jorge
A1  - Sharan, Malvika
A1  - Cruz, Ana Rita
A1  - Tawk, Caroline
A1  - Maudet, Claire
A1  - Mano, Miguel
A1  - Eulalio, Ana
T1  - Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia
JF  - PLoS Pathogens
N2  - MicroRNAs play an important role in the interplay between bacterial pathogens and host cells, participating as host defense mechanisms, as well as exploited by bacteria to subvert host cellular functions. Here, we show that microRNAs modulate infection by Shigella flexneri, a major causative agent of bacillary dysentery in humans. Specifically, we characterize the dual regulatory role of miR-29b-2-5p during infection, showing that this microRNA strongly favors Shigella infection by promoting both bacterial binding to host cells and intracellular replication. Using a combination of transcriptome analysis and targeted high-content RNAi screening, we identify UNC5C as a direct target of miR-29b-2-5p and show its pivotal role in the modulation of Shigella binding to host cells. MiR-29b-2-5p, through repression of UNC5C, strongly enhances filopodia formation thus increasing Shigella capture and promoting bacterial invasion. The increase of filopodia formation mediated by miR-29b-2-5p is dependent on RhoF and Cdc42 Rho-GTPases. Interestingly, the levels of miR-29b-2-5p, but not of other mature microRNAs from the same precursor, are decreased upon Shigella replication at late times post-infection, through degradation of the mature microRNA by the exonuclease PNPT1. While the relatively high basal levels of miR-29b-2-5p at the start of infection ensure efficient Shigella capture by host cell filopodia, dampening of miR-29b-2-5p levels later during infection may constitute a bacterial strategy to favor a balanced intracellular replication to avoid premature cell death and favor dissemination to neighboring cells, or alternatively, part of the host response to counteract Shigella infection. Overall, these findings reveal a previously unappreciated role of microRNAs, and in particular miR-29b-2-5p, in the interaction of Shigella with host cells.
KW  - hos tcells
KW  - Salmonellosis
KW  - Shigellosis
KW  - microRNAs
KW  - Shigella
KW  - small interfering RNAs
KW  - HeLa cells
KW  - Cell binding
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158204
VL  - 13
IS  - 4
ER  - 
TY  - JOUR
A1  - Eulalio, Ana
A1  - Fröhlich, Kathrin S.
A1  - Mano, Miguel
A1  - Giacca, Mauro
A1  - Vogel, Jörg
T1  - A Candidate Approach Implicates the Secreted Salmonella Effector Protein SpvB in P-Body Disassembly
N2  - P-bodies are dynamic aggregates of RNA and proteins involved in several post-transcriptional regulation processes. Pbodies have been shown to play important roles in regulating viral infection, whereas their interplay with bacterial pathogens, specifically intracellular bacteria that extensively manipulate host cell pathways, remains unknown. Here, we report that Salmonella infection induces P-body disassembly in a cell type-specific manner, and independently of previously characterized pathways such as inhibition of host cell RNA synthesis or microRNA-mediated gene silencing. We show that the Salmonella-induced P-body disassembly depends on the activation of the SPI-2 encoded type 3 secretion system, and that the secreted effector protein SpvB plays a major role in this process. P-body disruption is also induced by the related pathogen, Shigella flexneri, arguing that this might be a new mechanism by which intracellular bacterial pathogens subvert host cell function.
KW  - Salmonella
KW  - RNS
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68928
ER  -