Silencing by H-NS Potentiated the Evolution of Salmonella
Publication Date
November 06, 2014
Journal
PLOS Pathogens
Authors
Sabrina S. Ali, Jeremy Soo, Chitong Rao, Andrea S. Leung, et al
Volume
10
Issue
11
Pages
e1004500
DOI
https://dx.plos.org/10.1371/journal.ppat.1004500
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1004500
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/25375226
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223078
Europe PMC
http://europepmc.org/abstract/MED/25375226
Web of Science
000345515800025
Scopus
84912143308
Mendeley
http://www.mendeley.com/research/silencing-hns-potentiated-evolution-salmonella
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Mendeley | Further Information

{"title"=>"Silencing by H-NS Potentiated the Evolution of Salmonella", "type"=>"journal", "authors"=>[{"first_name"=>"Sabrina S.", "last_name"=>"Ali", "scopus_author_id"=>"55242079000"}, {"first_name"=>"Jeremy", "last_name"=>"Soo", "scopus_author_id"=>"56428752100"}, {"first_name"=>"Chitong", "last_name"=>"Rao", "scopus_author_id"=>"55744237300"}, {"first_name"=>"Andrea S.", "last_name"=>"Leung", "scopus_author_id"=>"24076186700"}, {"first_name"=>"David Hon Man", "last_name"=>"Ngai", "scopus_author_id"=>"56429425200"}, {"first_name"=>"Alexander W.", "last_name"=>"Ensminger", "scopus_author_id"=>"55375986500"}, {"first_name"=>"William Wiley", "last_name"=>"Navarre", "scopus_author_id"=>"6506622718"}], "year"=>2014, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"84912143308", "doi"=>"10.1371/journal.ppat.1004500", "pui"=>"600617200", "issn"=>"15537374", "pmid"=>"25375226", "isbn"=>"15537366", "scopus"=>"2-s2.0-84912143308"}, "id"=>"59af887b-768a-3118-b739-698d09f17c88", "abstract"=>"<title>Author Summary</title> <p>H-NS is an abundant DNA-binding protein found in enteric bacteria including the important pathogens <italic>Escherichia</italic>, <italic>Salmonella</italic>, <italic>Vibrio</italic>, and <italic>Yersinia</italic>, that plays a primary role in defending the bacterial genome by silencing AT-rich foreign genes. H-NS has been hypothesized to facilitate the evolution of bacterial species by acting as a buffer against the negative consequences that can occur when new genes are incorporated into pre-existing genetic landscapes. Here experimental evolution and whole-genome sequencing were employed to determine the factors underlying the severe growth defects displayed by <italic>Salmonella</italic> strains lacking H-NS. Through tracking the evolution of several independently derived mutant lineages, we find that compensatory mutations arise quickly and that they occur in loci related to virulence. A frequent outcome was loss of the <italic>Salmonella</italic> Pathogenicity Island-1, the defining genetic island of the genus <italic>Salmonella</italic>. Among other things these findings demonstrate that H-NS has enabled the birth of a new and important bacterial pathogen by buffering the fitness consequences caused by overexpression of SPI-1. These findings are likely generalizable to pathogens such as <italic>E. coli</italic>, <italic>Yersinia</italic>, <italic>Shigella</italic>, and <italic>Vibrio cholerae</italic>, all of which maintain a pool of “expensive” AT-rich virulence genes that are repressed by H-NS.</p>", "link"=>"http://www.mendeley.com/research/silencing-hns-potentiated-evolution-salmonella", "reader_count"=>63, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>8, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>21, "Student > Postgraduate"=>4, "Student > Master"=>13, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>8, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>21, "Student > Postgraduate"=>4, "Student > Master"=>13, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>11, "Agricultural and Biological Sciences"=>40, "Veterinary Science and Veterinary Medicine"=>1, "Physics and Astronomy"=>3, "Social Sciences"=>1, "Immunology and Microbiology"=>6}, "reader_count_by_subdiscipline"=>{"Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>40}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>11}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Belgium"=>1, "Ireland"=>1, "United Kingdom"=>1, "Germany"=>1}, "group_count"=>4}

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1780831"], "description"=>"<p>Oligonucleotides used in this study.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230272, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.t005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Oligonucleotides_used_in_this_study_/1230272", "title"=>"Oligonucleotides used in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780829"], "description"=>"<p>*Lineages A through F in this table are not the same as the A through F lineages derived from the first evolution experiment in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004500#ppat-1004500-t003\" target=\"_blank\">Tables 3</a>, <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004500#ppat-1004500-t004\" target=\"_blank\">4</a> or <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004500#ppat-1004500-g001\" target=\"_blank\">Figures 1</a>, <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004500#ppat-1004500-g002\" target=\"_blank\">2</a>, or <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004500#ppat-1004500-g003\" target=\"_blank\">3</a>.</p><p>Summary of <i>stpA</i> changes in second evolution experiment.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230270, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.t003", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_stpA_changes_in_second_evolution_experiment_/1230270", "title"=>"Summary of <i>stpA</i> changes in second evolution experiment.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780826"], "description"=>"<p>Purified StpA<sub>WT</sub>, StpA<sub>T37I</sub>, StpA<sub>M4T</sub>, StpA<sub>A77D</sub> proteins at a concentration of 100 µM were applied to a Superdex 200 10/300 GL column pre-equilibrated with 20 mM Tris pH 8, 1 M NaCl, 1 mM EDTA and 5% glycerol. The column was calibrated using globular protein standards ranging from 12.4 kDa to 443 kDa.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230267, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.g010", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analytical_gel_filtration_of_StpA_and_the_StpA_M4T_StpA_A77D_and_StpA_T37I_variants_/1230267", "title"=>"Analytical gel filtration of StpA and the StpA<sub>M4T</sub>, StpA<sub>A77D</sub>, and StpA<sub>T37I</sub> variants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780811"], "description"=>"<p>The mutations present in the <i>hns</i> mutant lineages at day 30 of the passaging period were detected by whole genome sequencing of the mixed populations. The identified genes of interest were PCR amplified directly from samples of the frozen daily culture stocks. The PCR products were sequenced and the relative signal intensities of the wild type vs. mutant alleles from each daily stock were used to estimate when the mutations emerged and became dominant in each population. Bars shaded in grey indicate the mutation was not detected via PCR sequencing, the orange bars indicate the mutation was detected in a fraction of the sequencing reads (<50%) and the blue bars indicate the mutant allele was predominant in the population (>50%). The large SPI-1 chromosomal deletions were detected by the appearance of a PCR product from the frozen stocks that spanned the deleted region. The green bars indicate detection of the SPI-1 deletions, the method employed did enable approximation of their abundance in the population.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230252, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Timeline_of_the_genetic_changes_in_the_hns_mutant_lineages_/1230252", "title"=>"Timeline of the genetic changes in the <i>hns</i> mutant lineages.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780808"], "description"=>"<p>(A) An <i>hns</i> mutant isolate prepared for microarray analysis incurred a spontaneous 10 kb deletion after minimal laboratory passage. The white arrows represent the deleted open reading frames (ORFs) and the black arrows represent the ORFs adjacent to the deleted region. (B) Schematic diagram illustrating the experimental design of the serial passaging experiment. Six independently derived <i>S.</i> Typhimurium <i>hns</i> mutant colonies were selected to initiate cultures of LB media, named <i>Δhns</i> lineages A–F. The <i>Δhns</i> lineages were serially passaged in parallel with six wild type cultures for 30 days (approx. 300 generations) and samples from each lineage were stocked daily. Genomic DNA from each population at Day 1 and Day 30 of the evolution period was prepared for Illumina sequencing. (C) Left hand side: growth curves of the <i>hns</i> mutant populations at day 1 (green curves) and day 30 (red curves) of the evolution period. Right hand side: growth curves of the wild type populations at day 1 (blue curves) and day 30 (grey curves) of the evolution period. Liquid growth assays were performed in a 96-well plate reader.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230249, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experimental_evolution_of_S_Typhimurium_hns_mutants_/1230249", "title"=>"Experimental evolution of <i>S.</i> Typhimurium <i>hns</i> mutants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780816"], "description"=>"<p>Expression levels of FLAG-tagged StpA variants were monitored by western blot analysis at early exponential phase (O.D. 600 nm 0.1) mid exponential phase (O.D. 600 nm 0.6) and early stationary phase (O.D. 600 nm 1.5). α-DnaK served as a loading control.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230257, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.g006", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_StpA_missense_mutations_do_not_affect_intracellular_protein_concentrations_/1230257", "title"=>"StpA missense mutations do not affect intracellular protein concentrations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780815"], "description"=>"<p>(A) Sequence alignment of H-NS and StpA from <i>S.</i> Typhimurium, conserved residues are highlighted in purple. The StpA amino acid substitutions acquired throughout the <i>hns</i> mutant passaging are indicated below the alignment in orange. (B) Plasmids harboring the StpA variants isolated from the passaged <i>Δhns</i> lineages were introduced into a <i>Δhns/ΔstpA</i> background and growth of the resulting strains was monitored in a 96-well plate reader. The wild type (black) and <i>Δhns/ΔstpA</i> strain expressing StpA<sub>WT</sub> (green) growth curves are the same in each panel. (C) Swarming motility of the same strains used in the growth assays were measured on soft agar plates following a 12 hour incubation period at 37°C. Expression of StpA<sub>T37I/E42</sub>, StpA<sub>M4T</sub>, StpA<sub>A77D</sub> and StpA<sub>K38Q/F76L</sub> restored motility by 16%, 30%, 44% and 34% respectively. Bars represent the average swarm diameter of three independent experiments and error bars represent the standard error.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230256, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Missense_mutations_in_the_H_NS_paralogue_StpA_partially_restore_the_impaired_growth_and_motility_phenotypes_of_hns_mutants_/1230256", "title"=>"Missense mutations in the H-NS paralogue StpA partially restore the impaired growth and motility phenotypes of <i>hns</i> mutants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780828"], "description"=>"<p>Summary of the genetic changes specific to the wild-type lineages.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230269, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.t002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_the_genetic_changes_specific_to_the_wild_type_lineages_/1230269", "title"=>"Summary of the genetic changes specific to the wild-type lineages.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780813"], "description"=>"<p>(A) Growth of a wild type <i>S.</i> Typhimurium (black curve) and a <i>Δhns</i> strain (green curve) was monitored in liquid media alongside wild type and <i>Δhns</i> strains harboring a 40 kb SPI-1 deletion (blue and red curves respectively). Elimination of the SPI-1 locus significantly increased growth of the <i>Δhns</i> strain and also provided a slight growth advantage in the wild type background. (B) Targeted disruption of <i>hilD</i>, the master SPI-1 activator produces a similar growth outcome as the SPI-1 deletion. Growth curves of the Δ<i>hilD</i> and <i>ΔhilD/Δhns</i> strains are represented in orange and purple respectively. The corresponding wild type (black) and <i>hns</i> mutant (green) growth curves are the same as panel A. Plotted is the average of three biological replicates and standard error (panels A and B).</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230254, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Disruption_of_SPI_1_expression_improves_fitness_of_an_hns_mutant_/1230254", "title"=>"Disruption of SPI-1 expression improves fitness of an <i>hns</i> mutant.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780827"], "description"=>"<p>Summary of the genetic changes specific to the <i>hns</i> mutant lineages.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230268, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.t001", "stats"=>{"downloads"=>13, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_the_genetic_changes_specific_to_the_hns_mutant_lineages_/1230268", "title"=>"Summary of the genetic changes specific to the <i>hns</i> mutant lineages.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780824"], "description"=>"<p>Electrophoretic mobility shift assays were conducted using purified H-NS, StpA<sub>WT</sub>, StpA<sub>T37I</sub>, StpA<sub>M4T</sub>, and StpA<sub>A77D</sub>. As indicated, the purified proteins were added to 289 bp AT-rich (%GC = 34) or 204 bp GC-rich (%GC = 74) model DNA fragments in increasing protein concentrations of 150 nM, 200 nM, 300 nM, 400 nM, and 500 nM. DNA/protein complexes were separated by 6% native polyacrylamide gel and stained with SYBR green. StpA complexes (▹) migrated alongside the top band of a nucleotide standard, while H-NS complexes (▸) migrated further into the gel as indicated.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230265, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.g009", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_StpA_M4T_and_StpA_A77D_form_DNA_protein_complexes_more_similar_to_H_NS_than_StpA_WT_/1230265", "title"=>"StpA<sub>M4T</sub> and StpA<sub>A77D</sub> form DNA-protein complexes more similar to H-NS than StpA<sub>WT</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780809"], "description"=>"<p>Throughout the 30-day evolution period, 5 out 6 <i>Δhns</i> lineages incurred 10–50 kb deletions in SPI-1. The lineages are arranged according to the size of the deletion they incurred. The deleted regions are marked with a dashed line. The grey box encompasses a region common to all five deletions that encoded the <i>prg/org</i> locus and the promoter and start codon of <i>hilD</i>. Lineage C did not acquire a deletion or any other mutations in the SPI-1 region.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230250, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_S_Typhimurium_hns_mutant_lineages_acquired_large_chromosomal_deletions_in_the_SPI_1_invasion_locus_/1230250", "title"=>"<i>S.</i> Typhimurium <i>hns</i> mutant lineages acquired large chromosomal deletions in the SPI-1 invasion locus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780821"], "description"=>"<p>(A) Swarming motility of the <b>s</b>trains expressing either StpA<sub>WT</sub> or individual StpA variants were measured on soft agar plates following a 12 hour incubation period at 37°C. Bars represent the average swarm diameter of three independent experiments and error bars represent the standard error. (B) Location of the StpA mutations mapped on the structure of the H-NS oliomerization domain. Orange residues indicate individual changes that could not impart H-NS functionality upon StpA.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230262, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.g008", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_StpA_mutants_that_partially_restore_the_motility_phenotype_in_hns_mutants_cluster_in_regions_/1230262", "title"=>"StpA mutants that partially restore the motility phenotype in <i>hns</i> mutants cluster in regions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780818"], "description"=>"<p>Transcript levels of four H-NS regulated genes, <i>proV</i>, <i>ssrA</i>, <i>yciG</i> and <i>hilA</i>, were measured by reverse transcriptase QPCR in a <i>Δhns/ΔstpA</i> strain expressing StpA<sub>WT</sub> or the variants StpA<sub>M4T</sub>, StpA<sub>A77D</sub> and StpA<sub>F21C</sub>. Transcript levels were also assayed in <i>Δhns</i> and <i>Δhns</i> complemented backgrounds (<i>Δhns</i>+pHNS).</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230259, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.g007", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Point_mutations_A77D_and_M4T_enhance_StpA_repression_of_select_hns_regulated_loci_/1230259", "title"=>"Point mutations A77D and M4T enhance StpA repression of select <i>hns</i> regulated loci.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780832", "https://ndownloader.figshare.com/files/1780833"], "description"=>"<div><p>The bacterial H-NS protein silences expression from sequences with higher AT-content than the host genome and is believed to buffer the fitness consequences associated with foreign gene acquisition. Loss of H-NS results in severe growth defects in <i>Salmonella</i>, but the underlying reasons were unclear. An experimental evolution approach was employed to determine which secondary mutations could compensate for the loss of H-NS in <i>Salmonella</i>. Six independently derived <i>S.</i> Typhimurium <i>hns</i> mutant strains were serially passaged for 300 generations prior to whole genome sequencing. Growth rates of all lineages dramatically improved during the course of the experiment. Each of the <i>hns</i> mutant lineages acquired missense mutations in the gene encoding the H-NS paralog StpA encoding a poorly understood H-NS paralog, while 5 of the mutant lineages acquired deletions in the genes encoding the <i>Salmonella</i> Pathogenicity Island-1 (SPI-1) Type 3 secretion system critical to invoke inflammation. We further demonstrate that SPI-1 misregulation is a primary contributor to the decreased fitness in <i>Salmonella hns</i> mutants. Three of the lineages acquired additional loss of function mutations in the PhoPQ virulence regulatory system. Similarly passaged wild type <i>Salmonella</i> lineages did not acquire these mutations. The <i>stpA</i> missense mutations arose in the oligomerization domain and generated proteins that could compensate for the loss of H-NS to varying degrees. StpA variants most able to functionally substitute for H-NS displayed altered DNA binding and oligomerization properties that resembled those of H-NS. These findings indicate that H-NS was central to the evolution of the Salmonellae by buffering the negative fitness consequences caused by the secretion system that is the defining characteristic of the species.</p></div>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230273, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1004500.s001", "https://dx.doi.org/10.1371/journal.ppat.1004500.s002"], "stats"=>{"downloads"=>5, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Silencing_by_H_NS_Potentiated_the_Evolution_of_Salmonella_/1230273", "title"=>"Silencing by H-NS Potentiated the Evolution of <i>Salmonella</i>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-11-06 02:45:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780830"], "description"=>"<p>Plasmids and strains used in this study.</p>", "links"=>[], "tags"=>["fitness consequences", "spi", "Salmonella hns mutants", "encoding", "dna", "stpA missense mutations", "type Salmonella lineages", "Salmonella pathogenicity island", "gene"], "article_id"=>1230271, "categories"=>["Biological Sciences"], "users"=>["Sabrina S. Ali", "Jeremy Soo", "Chitong Rao", "Andrea S. Leung", "David Hon-Man Ngai", "Alexander W. Ensminger", "William Wiley Navarre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004500.t004", "stats"=>{"downloads"=>15, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasmids_and_strains_used_in_this_study_/1230271", "title"=>"Plasmids and strains used in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-06 02:45:03"}

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