Identification - Characterization of New Virulence Factors of Listeria monocytogenes

srna.png

 

[Bécavin et al. MBio 2014]

Small RNAs in EGD-e. 154 known small RNAs (sRNAs) in EGD-e genome are displayed using CGView software according to their position in the genome. In red are the sRNAs which DNA sequence is conserved at less than 10% in EGD and 10403S strains.

 

 

excludons.png

[Sesto et al., Nature Reviews Microbiology 2013]

 

Schematic representations of excludons. a) The excludon paradigm. A general representation of an excludon locus, which consists of divergently oriented genes overlapped by a long antisense RNA (lasRNA), is shown. The overlapping lasRNA can act as a negative regulator for genes encoded on the opposite strand, but it can also be used as an mRNA for the genes encoded on the same strand. b-e) Examples of excludons in Listeria mono cytogenes. b) The flagellum biosynthesis excludon is regulated by the lasRNA Anti0677, which downregulates the expression of flagellum export apparatus genes (lmo0675–lmo0676–lmo0677) and concurrently drives expression of the gene encoding motility gene repressor (MogR), as the distal region of Anti0677 contains the coding sequence for this flagellum biosynthesis repressor. c) The permease–efflux pump excludon at the lmo0605/lmo0606–lmo0607–lmo0608 locus in L. monocytogenes is regulated by the lasRNA Anti0605, which overlaps and possibly negatively affects the expression of a gene encoding a MatE-family efflux pump (lmo0605) while acting as a second mRNA for the divergently oriented operon encoding two ABC transporters (lmo0607 and lmo0608). d) A second putative permease– efflux pump excludon in L. monocytogenes involves the lasRNA Anti1846, which overlaps the MatE-family efflux pump gene lmo1846 and acts as an mRNA for the permease encoded by lmo1845. e) L. monocytogenes also contains a possible carbon source utilization excludon involving the lasRNA Anti0424. This transcript overlaps a divergent sugar permease gene (lmo0424; predicted to be involved in glucose uptake) and then extends into an operon (encoded on the same strand as the lasRNA) containing genes encoding components of the fructose-specific phosphotransferase system (lmo0426–lmo0427–lmo0428).

 

 

 

 

mirna_network.png

 

[Archambaud et al., mBio 2013]

miRNA-mRNA network. Using Cytoscape, we highlighted, among the 5 miRNAs whose expression was affected by L. monocytogenes and the intestinal microbiota, a network linking miR-143 and miR-378 and the regulated host genes in the small intestine of conventional (CV) and germfree (GF) mice orally infected with L. monocytogenes 72 h p.i. As described in the text, miR-143 decreased upon infection in both CV and GF mice; in contrast, miR-378 decreased in CV mice but not in GF mice. Nodes represent infection-regulated miRNAs and genes; lines link each miRNA to its putative targets. Some of the predictions in mice were valid in humans (green circles). The color coding indicates the fold change of gene expression in Listeria-infected mice relative to the expression level in uninfected control mice. The differential expression levels of 11 genes were validated by RT-qPCR, as shown in Fig. 3B. Dotted lines show a gene that is similarly regulated in CV and GF mice.

 

 

prfa_regulation.png

[Cossart, PNAS 2011]

Two examples of complex regulation. (A) PrfA expression regulation

by an RNA thermosensor in the 5′UTR or a small RNA deriving from a SAM

riboswitch (25, 38). (B) Regulation of flagella expression.

 

 

listeria_evolution.png

 

[Cossart, PNAS 2011]

Phylogeny of the eight Listeria species. The tree depicted in continuous lines is based on nucleotide variation at 100 core genes, according to

den Bakker et al. (21). The three major L. monocytogenes lineages are indicated with Roman numerals. Dotted lines indicate that the branching order and distance leading to L. rocourtiae and L. grayi, the two most distant species, are currently undefined based on this dataset (generated by S. Brisse).

 

 

listeria_history.png

[Archambaud et al., Journal of Biology 2009]                  

Key dates and events, and related research areas on Listeria since its discovery in 1926.

 

 

 

small_rnas_expression.png

[Toledo-Arana et al., Nature 2009]

sRNA relative expression. Exp., exponential; Stat., stationary. Colour code bar indicates expression fold-change compared to the reference condition. Asterisk, absent in L. innocua. WT, wild type.

 

 

 

surface_proteins.png

[Bierne et al., Microbiology and Molecular Biology reviews 2007]

The different types of surface proteins found in L. monocytogenes. A prototype of each family is given.

 

 

 

surface_protein_list.jpg

[Cabanes et al., Trends in Microbiology 2002]

Alignment of Listeria monocytogenes (a) internalin-like LPXTG proteins; (b) other LPXTG proteins; (c) GW proteins; and (d) P60-like proteins. The numbers within domains indicate the number of repeats. Proteins absent from Listeria innocua are indicated by an asterix.

 

 

 

 

prfa_thermosensor.png

[Johansson et al., Cell 2002]

Model of the Mechanism Underlying Thermoregulated Expression of PrfA. The prfA-UTR forms a secondary structure at low temperatures (_30_C) masking the ribosomal region of prfA, thus preventing the binding of the ribosome. PrfA is not translated and virulence genes are not expressed. At high temperatures (_37_C) the prfA-UTR partially melts, and thereby permits binding of the ribosome to the Shine-Dalgarno sequence. Translation of prfA allows virulence gene expression.

 

 

 

prfa_regulon.png

[Milohanic et al., Molecular Microbiology 2002]

The PrfA regulon. The key virulence genes are under the regulation of the pleiotropic activator protein PrfA, a protein similar to the cyclic AMP receptor protein, CAP in E. coli

 

listeria_genomes.png

[Glaser et al., Science 2001]

Circular genome maps of L. monocytogenes EGD-e and L. innocua CLIP 11262, showing the position and orientation of genes. From the outside: Circles 1 and 2, L. innocua and L. monocytogenes genes on the ? and – strands, respectively. Color code: green, L. innocua genes; red, L. monocytogenes genes; black, genes specific for L. monocytogenes or L. innocua, respectively; orange, rRNA operons; purple, prophages. Numbers on the second circle indicate the position of known virulence genes: 1, virulence locus ( prfA-plcA-hly-mpl-actA-plcB); 2, clpC;3, inlAB;4, iap;5, dal;6, clpE;7, lisRK;8, dat;9, inlC; 10, arpJ; 11, clpP; 12, ami; 13, bvrABC. Circle 3, G/C bias (G?C/G–C) of L. monocytogenes. Circle 4, G?C content of L. monocyto- genes (?32.5% G?C in light yellow, 32.5 to 43.5% in yellow, and ?43.5% G?Cindark yellow). The scale in megabases is indicated on the outside of the genome circles, with the origin of replication at position 0.

 

Updated on 13/05/2014

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