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Comparative Transcriptome Analysis of Listeria monocytogenes Strains of the Two Major Lineages Reveals Differences in Virulence, Cell Wall, and Stress Response ^,

Patricia Severino ,^1, Olivier Dussurget ,^2,3,4, Ricardo Z. N. Vêncio,^5, Emilie Dumas,⁶ Patricia Garrido,¹ Gabriel Padilla,⁷ Pascal Piveteau,⁸ Jean-Paul Lemaître,⁸ Frank Kunst,¹ Philippe Glaser,¹ and Carmen Buchrieser^1*

Unité de Génomique des Microorganismes Pathogènes and CNRS URA 2171,¹ Unité des Interactions Bactéries-Cellules, Institut Pasteur, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, France,² INSERM U604, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France,³ INRA USC2020, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France,⁴ Computational Biology Group, Institute for Systems Biology, 1441 North 34th Street, Seattle, Washington,⁵ UR484 Microbiologie, Equipe Qualité et Sécurité des Aliments (QuaSA), INRA de Clermont-Ferrand/Theix, F-63122 Saint-Genès Champanelle, France,⁶ Departamento de Microbiologia, Instituto de Ciências Biomédicas da Universidade de São Paulo, 05508-900 São Paulo, Brazil,⁷ Laboratoire de Microbiologie, INRA UMR1232, 1 Esplanade Erasme, F-21000 Dijon, France⁸

Received 22 November 2006/ Accepted 6 August 2007

Listeria monocytogenes is a food-borne, opportunistic, bacterial pathogen causing a wide spectrum of diseases, including meningitis, septicemia, abortion, and gastroenteritis, in humans and animals. Among the 13 L. monocytogenes serovars described, human listeriosis is mostly associated with strains of serovars 4b, 1/2b, and 1/2a. Within the species L. monocytogenes, three phylogenetic lineages are described. Serovar 1/2a belongs to phylogenetic lineage I, while serovars 4b and 1/2b group in phylogenetic lineage II. To explore the role of gene expression in the adaptation of L. monocytogenes strains of these two major lineages to different environments, as well as in virulence, we performed whole-genome expression profiling of six L. monocytogenes isolates of serovars 4b, 1/2b, and 1/2a of distinct origins, using a newly constructed Listeria multigenome DNA array. Comparison of the global gene expression profiles revealed differences among strains. The expression profiles of two strains having distinct 50% lethal doses, as assessed in the mouse model, were further analyzed. Gene ontology term enrichment analysis of the differentially expressed genes identified differences in protein-, nucleic acid-, carbon metabolism-, and virulence-related gene expression. Comparison of the expression profiles of the core genomes of all strains revealed differences between the two lineages with respect to cell wall synthesis, the stress-related sigma B regulon and virulence-related genes. These findings suggest different patterns of interaction with host cells and the environment, key factors for host colonization and survival in the environment.

Published ahead of print on 17 August 2007.

Supplemental material for this article may be found at http://aem.asm.org/.

Present address: Instituto de Ensino e Pesquisa Albert Einstein, Hospital Albert Einstein, 05651-901 São Paulo, Brazil.

Both authors contributed equally to this work.