MouR controls the expression of the Listeria monocytogenes Agr system and mediates virulence

The foodborne pathogen Listeria monocytogenes (Lm) causes invasive infection in susceptible ani- mals and humans. To survive and proliferate within hosts, this facultative intracellular pathogen tightly coordinates the expression of a complex regulatory network that controls the expression of virulence fac- tors. Here, we identified and characterized MouR, a novel virulence regulator of Lm. Through RNA-seq transcriptomic analysis, we determined the MouR regulon and demonstrated how MouR positively con- trols the expression of the Agr quorum sensing sys- tem (agrBDCA) of Lm. The MouR three-dimensional structure revealed a dimeric DNA-binding transcrip- tion factor belonging to the VanR class of the GntR superfamily of regulatory proteins. We also showed that by directly binding to the agr promoter region, MouR ultimately modulates chitinase activity and biofilm formation. Importantly, we demonstrated by in vitro cell invasion assays and in vivo mice infec- tions the role of MouR in Lm virulence.Peer reviewe

Modular neural networks for analysis of flow cytometry data

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Bax Is Activated during Rotavirus-Induced Apoptosis through the Mitochondrial Pathway▿

Rotaviruses are the leading cause of infantile viral gastroenteritis worldwide. Mature enterocytes of the small intestine infected by rotavirus undergo apoptosis, and their replacement by less differentiated dividing cells probably leads to defective absorptive function of the intestinal epithelium, which, in turn, contributes to osmotic diarrhea and rotavirus pathogenesis. Here we show that infection of MA104 cells by the simian rhesus rotavirus strain RRV induced caspase-3 activation, DNA fragmentation, and cleavage of poly(ADP-ribose) polymerase; all three phenomena are features of apoptosis. RRV induced the release of cytochrome c from mitochondria to the cytosol, indicating that the mitochondrial apoptotic pathway was activated. RRV infection of MA104 cells activated Bax, a proapoptotic member of the Bcl-2 family, as revealed by its conformational change. Most importantly, Bax-specific small interfering RNAs partially inhibited cytochrome c release in RRV-infected cells. Thus, mitochondrial dysfunction induced by rotavirus is Bax dependent. Apoptosis presumably leads to impaired intestinal functions, so our findings contribute to improving our understanding of rotavirus pathogenesis at the cellular level

Development of a Taqman RT-PCR assay for the detection and quantification of negatively stranded RNA of human enteroviruses: Evidence for false-priming and improvement by tagged RT-PCR.

International audienceHuman enteroviruses are among the most common viruses infecting humans. These viruses are known to be able to infect a wide range of tissues and are believed to establish persistent infections. Enteroviruses are positive-sense single-stranded RNA viruses whose replication involves the synthesis of negative strand intermediates. Therefore, the specific detection of negatively stranded viral RNA in tissues or cells is a reliable marker of active enteroviral replication. The present report presents the development of a real-time RT-PCR allowing the specific detection and quantification of negatively stranded viral RNA. Since it was known that specific amplification of single-stranded RNA can be made difficult by false-priming events leading to false-positive or overestimated results, the assay was developed by using a tagged RT primer. This tagged RT-PCR was shown to be able to amplify specifically negative RNA of enteroviruses grown in cell cultures by preventing the amplification of cDNAs generated by false-priming

Early Phosphatidylinositol 3-Kinase/Akt Pathway Activation Limits Poliovirus-Induced JNK-Mediated Cell Death▿

Poliovirus (PV)-induced apoptosis seems to play a major role in tissue injury in the central nervous system (CNS). We have previously shown that this process involves PV-induced Bax-dependent mitochondrial dysfunction mediated by early JNK activation in IMR5 neuroblastoma cells. We showed here that PV simultaneously activates the phosphatidylinositol 3-kinase (PI3K)/Akt survival signaling pathway in these cells, limiting the extent of JNK activation and thereby cell death. JNK inhibition is associated with PI3K-dependent negative regulation of the apoptosis signal-regulating kinase 1, which acts upstream from JNK in PV-infected IMR5 cells. In poliomyelitis, this survival pathway may limit the spread of PV-induced damage in the CNS

Poliovirus et Apoptose

Le poliovirus est l'agent responsable de la poliomyélite paralytique aigüe. Les paralysies flasques caractéristiques de la poliomyélite résultent de la destruction des neurones moteurs, les cellules cibles spécifiques du poliovirus dans le système nerveux central (SNC). Le développement de nouveaux modèles animaux et cellulaires a permis d'étudier les étapes clés de la pathogénèse de la poliomyélite à un niveau moléculaire. En particulier il a été montré chez la souris que l'induction de l'apoptose est un élément important de l'atteinte du SNC des animaux paralysés suite à l'infection par le poliovirus. Dans cette revue, la biologie moléculaire du poliovirus et la pathogénèse de la poliomyélite paralytique seront décrites brièvement et plusieurs modèles d'apoptose induite par le poliovirus avec son récepteur cellulaire dans l'apoptose sera également considéré