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{"title"=>"In vivo transcriptional profiling of Listeria monocytogenes and mutagenesis identify new virulence factors involved in infection", "type"=>"journal", "authors"=>[{"first_name"=>"Ana", "last_name"=>"Camejo", "scopus_author_id"=>"26648108400"}, {"first_name"=>"Carmen", "last_name"=>"Buchrieser", "scopus_author_id"=>"7003363257"}, {"first_name"=>"Elisabeth", "last_name"=>"Couvé", "scopus_author_id"=>"6603770774"}, {"first_name"=>"Filipe", "last_name"=>"Carvalho", "scopus_author_id"=>"36928314000"}, {"first_name"=>"Olga", "last_name"=>"Reis", "scopus_author_id"=>"26649172800"}, {"first_name"=>"Pierre", "last_name"=>"Ferreira", "scopus_author_id"=>"26648494300"}, {"first_name"=>"Sandra", "last_name"=>"Sousa", "scopus_author_id"=>"35235064300"}, {"first_name"=>"Pascale", "last_name"=>"Cossart", "scopus_author_id"=>"7103021053"}, {"first_name"=>"Didier", "last_name"=>"Cabanes", "scopus_author_id"=>"6602317562"}], "year"=>2009, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537366", "isbn"=>"1553-7374 (Electronic)\\n1553-7366 (Linking)", "pmid"=>"19478867", "scopus"=>"2-s2.0-67249147690", "doi"=>"10.1371/journal.ppat.1000449", "sgr"=>"67249147690", "pui"=>"354743706"}, "id"=>"89ee8b0f-14e5-3c98-88cd-120061ffb25a", "abstract"=>"Listeria monocytogenes is a human intracellular pathogen able to colonize host tissues after ingestion of contaminated food, causing severe invasive infections. In order to gain a better understanding of the nature of host-pathogen interactions, we studied the L. monocytogenes genome expression during mouse infection. In the spleen of infected mice, approximately 20% of the Listeria genome is differentially expressed, essentially through gene activation, as compared to exponential growth in rich broth medium. Data presented here show that, during infection, Listeria is in an active multiplication phase, as revealed by the high expression of genes involved in replication, cell division and multiplication. In vivo bacterial growth requires increased expression of genes involved in adaptation of the bacterial metabolism and stress responses, in particular to oxidative stress. Listeria interaction with its host induces cell wall metabolism and surface expression of virulence factors. During infection, L. monocytogenes also activates subversion mechanisms of host defenses, including resistance to cationic peptides, peptidoglycan modifications and release of muramyl peptides. We show that the in vivo differential expression of the Listeria genome is coordinated by a complex regulatory network, with a central role for the PrfA-SigB interplay. In particular, L. monocytogenes up regulates in vivo the two major virulence regulators, PrfA and VirR, and their downstream effectors. Mutagenesis of in vivo induced genes allowed the identification of novel L. monocytogenes virulence factors, including an LPXTG surface protein, suggesting a role for S-layer glycoproteins and for cadmium efflux system in Listeria virulence.", "link"=>"http://www.mendeley.com/research/vivo-transcriptional-profiling-listeria-monocytogenes-mutagenesis-identify-new-virulence-factors-inv", "reader_count"=>141, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Researcher"=>35, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>50, "Student > Postgraduate"=>5, "Student > Master"=>16, "Other"=>4, "Student > Bachelor"=>8, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>3, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Researcher"=>35, "Student > Doctoral Student"=>6, "Student > Ph. D. 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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/443617", "https://ndownloader.figshare.com/files/443661", "https://ndownloader.figshare.com/files/443712", "https://ndownloader.figshare.com/files/443764", "https://ndownloader.figshare.com/files/443897", "https://ndownloader.figshare.com/files/444013", "https://ndownloader.figshare.com/files/444062", "https://ndownloader.figshare.com/files/444118", "https://ndownloader.figshare.com/files/444184", "https://ndownloader.figshare.com/files/444223", "https://ndownloader.figshare.com/files/444288"], "description"=>"<div><p><em>Listeria monocytogenes</em> is a human intracellular pathogen able to colonize host tissues after ingestion of contaminated food, causing severe invasive infections. In order to gain a better understanding of the nature of host–pathogen interactions, we studied the <em>L. monocytogenes</em> genome expression during mouse infection. In the spleen of infected mice, ≈20% of the <em>Listeria</em> genome is differentially expressed, essentially through gene activation, as compared to exponential growth in rich broth medium. Data presented here show that, during infection, <em>Listeria</em> is in an active multiplication phase, as revealed by the high expression of genes involved in replication, cell division and multiplication. <em>In vivo</em> bacterial growth requires increased expression of genes involved in adaptation of the bacterial metabolism and stress responses, in particular to oxidative stress. <em>Listeria</em> interaction with its host induces cell wall metabolism and surface expression of virulence factors. During infection, <em>L. monocytogenes</em> also activates subversion mechanisms of host defenses, including resistance to cationic peptides, peptidoglycan modifications and release of muramyl peptides. We show that the <em>in vivo</em> differential expression of the <em>Listeria</em> genome is coordinated by a complex regulatory network, with a central role for the PrfA-SigB interplay. In particular, <em>L. monocytogenes</em> up regulates <em>in vivo</em> the two major virulence regulators, PrfA and VirR, and their downstream effectors. Mutagenesis of <em>in vivo</em> induced genes allowed the identification of novel <em>L. monocytogenes</em> virulence factors, including an LPXTG surface protein, suggesting a role for S-layer glycoproteins and for cadmium efflux system in <em>Listeria</em> virulence.</p></div>", "links"=>[], "tags"=>["transcriptional", "profiling", "mutagenesis", "virulence", "factors"], "article_id"=>147445, "categories"=>["Cancer", "Microbiology", "Biological Sciences"], "users"=>["Ana Camejo", "Carmen Buchrieser", "Elisabeth Couvé", "Filipe Carvalho", "Olga Reis", "Pierre Ferreira", "Sandra Sousa", "Pascale Cossart", "Didier Cabanes"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000449.s001", "https://dx.doi.org/10.1371/journal.ppat.1000449.s002", "https://dx.doi.org/10.1371/journal.ppat.1000449.s003", "https://dx.doi.org/10.1371/journal.ppat.1000449.s004", "https://dx.doi.org/10.1371/journal.ppat.1000449.s005", "https://dx.doi.org/10.1371/journal.ppat.1000449.s006", "https://dx.doi.org/10.1371/journal.ppat.1000449.s007", "https://dx.doi.org/10.1371/journal.ppat.1000449.s008", "https://dx.doi.org/10.1371/journal.ppat.1000449.s009", "https://dx.doi.org/10.1371/journal.ppat.1000449.s010", "https://dx.doi.org/10.1371/journal.ppat.1000449.s011"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_Vivo_Transcriptional_Profiling_of_Listeria_monocytogenes_and_Mutagenesis_Identify_New_Virulence_Factors_Involved_in_Infection/147445", "title"=>"<em>In Vivo</em> Transcriptional Profiling of <em>Listeria monocytogenes</em> and Mutagenesis Identify New Virulence Factors Involved in Infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-05-29 02:04:05"}
• {"files"=>["https://ndownloader.figshare.com/files/896791"], "description"=>"<p>(A) Analysis of the impact of the <i>in vitro</i> culture conditions used as reference. The expression of known and potential virulence factors was analyzed in BHI at 37°C in exponential (BHI log) or stationary (BHI stat) growth phase, or in minimal medium in exponential growth phase (MM log) by real-time RT-PCR, and normalized to expression in mouse spleen. (B) Validation of macroarray data by real-time RT-PCR. Fold changes in <i>in vivo</i> gene expression 48 h p.i. compared to that in BHI were measured by macroarray and real-time RT-PCR, log transformed and compared for correlation analysis. (C) Analysis of the effect of the RNA extraction method on <i>L. monocytogenes</i> gene expression. RNAs from bacteria grown in BHI were prepared using the standard and adapted procedures for RNA extraction. The relative expression of potential virulence genes, cold shock genes and known virulence genes was determined by real-time RT-PCR.</p>", "links"=>[], "tags"=>["computational biology/transcriptional regulation", "infectious diseases/bacterial infections", "microbiology/cellular microbiology and pathogenesis"], "article_id"=>567240, "categories"=>["Infectious Diseases", "Microbiology", "Computational Biology"], "users"=>["Ana Camejo", "Carmen Buchrieser", "Elisabeth Couvé", "Filipe Carvalho", "Olga Reis", "Pierre Ferreira", "Sandra Sousa", "Pascale Cossart", "Didier Cabanes"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000449.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Macroarray_validations_/567240", "title"=>"Macroarray validations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-29 02:00:40"}
• {"files"=>["https://ndownloader.figshare.com/files/896871"], "description"=>"<p>Venn diagrams showing the distribution of the up and down regulated genes at the three <i>in vivo</i> infection time points.</p>", "links"=>[], "tags"=>["diagrams", "regulated", "genes"], "article_id"=>567324, "categories"=>["Infectious Diseases", "Microbiology", "Computational Biology"], "users"=>["Ana Camejo", "Carmen Buchrieser", "Elisabeth Couvé", "Filipe Carvalho", "Olga Reis", "Pierre Ferreira", "Sandra Sousa", "Pascale Cossart", "Didier Cabanes"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000449.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Venn_diagrams_showing_the_distribution_of_the_up_and_down_regulated_genes_at_the_three_in_vivo_infection_time_points_/567324", "title"=>"Venn diagrams showing the distribution of the up and down regulated genes at the three <i>in vivo</i> infection time points.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-29 02:02:04"}
• {"files"=>["https://ndownloader.figshare.com/files/896969"], "description"=>"<p>Differentially regulated genes of <i>L. monocytogenes</i> EGDe obtained from temporal transcriptome profiling experiments, classified in functional categories.</p>", "links"=>[], "tags"=>["regulated", "genes", "egde", "temporal", "transcriptome", "profiling", "classified"], "article_id"=>567418, "categories"=>["Infectious Diseases", "Microbiology", "Computational Biology"], "users"=>["Ana Camejo", "Carmen Buchrieser", "Elisabeth Couvé", "Filipe Carvalho", "Olga Reis", "Pierre Ferreira", "Sandra Sousa", "Pascale Cossart", "Didier Cabanes"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000449.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differentially_regulated_genes_of_L_monocytogenes_EGDe_obtained_from_temporal_transcriptome_profiling_experiments_classified_in_functional_categories_/567418", "title"=>"Differentially regulated genes of <i>L. monocytogenes</i> EGDe obtained from temporal transcriptome profiling experiments, classified in functional categories.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-29 02:03:38"}
• {"files"=>["https://ndownloader.figshare.com/files/897057"], "description"=>"<p>Expression during mouse spleen infection of the 31 known virulence genes differentially regulated <i>in vivo</i>. A peak of expression was observed for the majority of these virulence genes 48 h p.i. All measurements are relative to culture in exponential phase in BHI. Genes were selected for this analysis when their expression deviated from BHI by at least a factor of 2.0 in at least one time point. The image was produced as described in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000449#s4\" target=\"_blank\">Materials and Methods</a>. Each gene is represented by a single row of colored boxes; each time point is represented by a single column.</p>", "links"=>[], "tags"=>["virulence"], "article_id"=>567514, "categories"=>["Infectious Diseases", "Microbiology", "Computational Biology"], "users"=>["Ana Camejo", "Carmen Buchrieser", "Elisabeth Couvé", "Filipe Carvalho", "Olga Reis", "Pierre Ferreira", "Sandra Sousa", "Pascale Cossart", "Didier Cabanes"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000449.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_expression_of_virulence_genes_/567514", "title"=>"<i>In vivo</i> expression of virulence genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-29 02:05:14"}
• {"files"=>["https://ndownloader.figshare.com/files/897114"], "description"=>"<p>BALB/c mice were intravenously inoculated with 10⁴ CFUs. The number of bacteria in the spleen (A) and liver (B) of mice was determined at 72 h post-infection. A <i>prsA</i> mutant was constructed and used as control. Five mice for each bacterial strain. Statistically significant differences are indicated as compared to wild type strain: ** = <i>P</i><0.01, *** = <i>P</i><0.001.</p>", "links"=>[], "tags"=>["characterization"], "article_id"=>567573, "categories"=>["Infectious Diseases", "Microbiology", "Computational Biology"], "users"=>["Ana Camejo", "Carmen Buchrieser", "Elisabeth Couvé", "Filipe Carvalho", "Olga Reis", "Pierre Ferreira", "Sandra Sousa", "Pascale Cossart", "Didier Cabanes"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000449.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_characterization_of_new_Listeria_mutants_/567573", "title"=>"<i>In vivo</i> characterization of new <i>Listeria</i> mutants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-29 02:06:13"}
• {"files"=>["https://ndownloader.figshare.com/files/897204"], "description"=>"<p>(A) Growth curves of <i>L. monocytogenes</i> EGDe strains in BHI at 37°C with shaking. (B) Intracellular behavior of <i>L. monocytogenes</i> EGDe strains in J774 cultured cells.</p>", "links"=>[], "tags"=>["computational biology/transcriptional regulation", "infectious diseases/bacterial infections", "microbiology/cellular microbiology and pathogenesis"], "article_id"=>567655, "categories"=>["Infectious Diseases", "Microbiology", "Computational Biology"], "users"=>["Ana Camejo", "Carmen Buchrieser", "Elisabeth Couvé", "Filipe Carvalho", "Olga Reis", "Pierre Ferreira", "Sandra Sousa", "Pascale Cossart", "Didier Cabanes"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000449.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vitro_behavior_of_L_monocytogenes_mutants_/567655", "title"=>"<i>In vitro</i> behavior of <i>L. monocytogenes</i> mutants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-29 02:07:35"}
• {"files"=>["https://ndownloader.figshare.com/files/897327"], "description"=>"<p>BALB/c mice were intravenously inoculated with 10⁴ CFUs. The number of bacteria in the spleen (A) and liver (B) of mice was determined at 72 h post-infection. Five mice for each bacterial strain. Statistically significant differences are indicated as compared to the corresponding mutant for complemented strains: * = <i>P</i><0.05, ** = <i>P</i><0.01, *** = <i>P</i><0.001.</p>", "links"=>[], "tags"=>["complementation"], "article_id"=>567785, "categories"=>["Infectious Diseases", "Microbiology", "Computational Biology"], "users"=>["Ana Camejo", "Carmen Buchrieser", "Elisabeth Couvé", "Filipe Carvalho", "Olga Reis", "Pierre Ferreira", "Sandra Sousa", "Pascale Cossart", "Didier Cabanes"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000449.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_complementation_of_new_Listeria_mutants_/567785", "title"=>"<i>In vivo</i> complementation of new <i>Listeria</i> mutants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-29 02:09:45"}
• {"files"=>["https://ndownloader.figshare.com/files/897419"], "description"=>"<p><i>L. monocytogenes</i> EGDe cell surface encoding genes differentially regulated in the host.</p>", "links"=>[], "tags"=>["egde", "encoding", "genes", "differentially", "regulated"], "article_id"=>567866, "categories"=>["Infectious Diseases", "Microbiology", "Computational Biology"], "users"=>["Ana Camejo", "Carmen Buchrieser", "Elisabeth Couvé", "Filipe Carvalho", "Olga Reis", "Pierre Ferreira", "Sandra Sousa", "Pascale Cossart", "Didier Cabanes"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000449.t005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_L_monocytogenes_EGDe_cell_surface_encoding_genes_differentially_regulated_in_the_host_/567866", "title"=>"<i>L. monocytogenes</i> EGDe cell surface encoding genes differentially regulated in the host.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-05-29 02:11:06"}
• {"files"=>["https://ndownloader.figshare.com/files/897464"], "description"=>"<p><i>L. monocytogenes</i> EGDe genes implicated in cell wall metabolism and differentially regulated in the host.</p>", "links"=>[], "tags"=>["egde", "genes", "implicated", "metabolism", "differentially", "regulated"], "article_id"=>567906, "categories"=>["Infectious Diseases", "Microbiology", "Computational Biology"], "users"=>["Ana Camejo", "Carmen Buchrieser", "Elisabeth Couvé", "Filipe Carvalho", "Olga Reis", "Pierre Ferreira", "Sandra Sousa", "Pascale Cossart", "Didier Cabanes"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1000449.t004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_L_monocytogenes_EGDe_genes_implicated_in_cell_wall_metabolism_and_differentially_regulated_in_the_host_/567906", "title"=>"<i>L. monocytogenes</i> EGDe genes implicated in cell wall metabolism and differentially regulated in the host.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-05-29 02:11:46"}
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F1000Prime