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The Listeria transcriptional landscape from saprophytism to virulence


The bacterium Listeria monocytogenes is ubiquitous in the environment and can lead to severe food-borne infections. It has recently emerged as a multifaceted model in pathogenesis. However, how this bacterium switches from a saprophyte to a pathogen is largely unknown. Here, using tiling arrays and RNAs from wild-type and mutant bacteria grown in vitro, ex vivo and in vivo, we have analysed the transcription of its entire genome. We provide the complete Listeria operon map and have uncovered far more diverse types of RNAs than expected: in addition to 50 small RNAs (<500 nucleotides), at least two of which are involved in virulence in mice, we have identified antisense RNAs covering several open-reading frames and long overlapping 5′ and 3′ untranslated regions. We discovered that riboswitches can act as terminators for upstream genes. When Listeria reaches the host intestinal lumen, an extensive transcriptional reshaping occurs with a SigB-mediated activation of virulence genes. In contrast, in the blood, PrfA controls transcription of virulence genes. Remarkably, several non-coding RNAs absent in the non-pathogenic species Listeria innocua exhibit the same expression patterns as the virulence genes. Together, our data unravel successive and coordinated global transcriptional changes during infection and point to previously unknown regulatory mechanisms in bacteria.

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Figure 1: L. monocytogenes operon map and small RNAs.
Figure 2: Functional analysis of Rli38, RliB and LysRS.
Figure 3: Cis-regulatory RNA-elements.
Figure 4: The MogR locus.
Figure 5: Gene expression analysis.
Figure 6: Virulence gene expression and gene clusters.

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Data deposits

Raw data are available from ArrayExpress ( under accession numbers E-MEXP-2138 for gene expression sub-array analysis and E-MEXP-2142 for tiling sub-array analysis.


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We are grateful to E. Charpentier and the members of her group for providing the RACE protocol. We thank L. Frangeul for helping with L. monocytogenes annotation files. J.J. is supported by the Swedish Research Council grants K2008-58X-15144-05-3 and 621-2006-4450 and EU (BacRNA 2005 Contract N° 018618). Work in the laboratory of P.C. received financial support from Institut Pasteur (GPH 9), Inserm, INRA, EU (BacRNA 2005-018618), ANR (ANR-05-MIIM-026-01) and ERC (Advanced Grant 233348). A.T.-A. was an EMBO long-term fellow. P.C. is an international research scholar of the Howard Hughes Medical Institute.

Author Contributions P.C. planned the project. A.T.-A., O.D., M.L. and P.C. designed the research. A.T.-A., O.D., G.N., N.S., H.G.-R., D.B., E.L., J.G., T.T., K.V., M.-A.N., G.S. and M.L. performed the experiments. A.T.-A., O.D., M.B., M.V., B.R., J.-Y.C., M.L., J.J. and P.C. analysed the experiments. A.T.-A., O.D. and P.C. wrote the paper and co-authors commented on it.

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Correspondence to Pascale Cossart.

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Toledo-Arana, A., Dussurget, O., Nikitas, G. et al. The Listeria transcriptional landscape from saprophytism to virulence. Nature 459, 950–956 (2009).

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