RocA Truncation Underpins Hyper-Encapsulation, Carriage Longevity and Transmissibility of Serotype M18 Group A Streptococci
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{"title"=>"RocA Truncation Underpins Hyper-Encapsulation, Carriage Longevity and Transmissibility of Serotype M18 Group A Streptococci", "type"=>"journal", "authors"=>[{"first_name"=>"Nicola N.", "last_name"=>"Lynskey", "scopus_author_id"=>"47461485400"}, {"first_name"=>"David", "last_name"=>"Goulding", "scopus_author_id"=>"7003436963"}, {"first_name"=>"Magdalena", "last_name"=>"Gierula", "scopus_author_id"=>"39761640900"}, {"first_name"=>"Claire E.", "last_name"=>"Turner", "scopus_author_id"=>"8538775700"}, {"first_name"=>"Gordon", "last_name"=>"Dougan", "scopus_author_id"=>"7102366949"}, {"first_name"=>"Robert J.", "last_name"=>"Edwards", "scopus_author_id"=>"55242500900"}, {"first_name"=>"Shiranee", "last_name"=>"Sriskandan", "scopus_author_id"=>"6701743013"}], "year"=>2013, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "pmid"=>"24367267", "scopus"=>"2-s2.0-84892851667", "doi"=>"10.1371/journal.ppat.1003842", "pui"=>"372180086", "isbn"=>"1553-7366", "sgr"=>"84892851667"}, "id"=>"0fe3f30d-3ab0-35ba-9410-94af2b638b79", "abstract"=>"Group A streptococcal isolates of serotype M18 are historically associated with epidemic waves of pharyngitis and the non-suppurative immune sequela rheumatic fever. The serotype is defined by a unique, highly encapsulated phenotype, yet the molecular basis for this unusual colony morphology is unknown. Here we identify a truncation in the regulatory protein RocA, unique to and conserved within our serotype M18 GAS collection, and demonstrate that it underlies the characteristic M18 capsule phenotype. Reciprocal allelic exchange mutagenesis of rocA between M18 GAS and M89 GAS demonstrated that truncation of RocA was both necessary and sufficient for hyper-encapsulation via up-regulation of both precursors required for hyaluronic acid synthesis. Although RocA was shown to positively enhance covR transcription, quantitative proteomics revealed RocA to be a metabolic regulator with activity beyond the CovR/S regulon. M18 GAS demonstrated a uniquely protuberant chain formation following culture on agar that was dependent on excess capsule and the RocA mutation. Correction of the M18 rocA mutation reduced GAS survival in human blood, and in vivo naso-pharyngeal carriage longevity in a murine model, with an associated drop in bacterial airborne transmission during infection. In summary, a naturally occurring truncation in a regulator explains the encapsulation phenotype, carriage longevity and transmissibility of M18 GAS, highlighting the close interrelation of metabolism, capsule and virulence.", "link"=>"http://www.mendeley.com/research/roca-truncation-underpins-hyperencapsulation-carriage-longevity-transmissibility-serotype-m18-group", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>9, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>9, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>17, "Medicine and Dentistry"=>2, "Social Sciences"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>17}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Hong Kong"=>1, "United States"=>1, "United Kingdom"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1323261"], "description"=>"<p>Characterization of serotype M18 GAS by comparison with representatives of each of six major serotypes (n = 5 isolates/group). (A) Inter-serotype comparison of absolute copy number for <i>hasA</i> standardized to housekeeping gene <i>gyrA</i>. Line shows median (Kruskal-Wallis; *** = p<0.001). (B) Inter-serotype comparison of capsular HA expression across all serotypes by an ELISA-based assay. Line shows median (Kruskal-Wallis; *** = p<0.001). (C) Inter-serotype comparison of absolute transcript copy number for <i>covR</i> and <i>covS</i> standardized to house-keeping gene <i>gyrA</i>. Line shows median (Kruskal-Wallis; p = NS). (D) Inter-serotype comparison of duration of nasopharyngeal shedding of pharyngitis-associated serotypes M4, M6, M12 and M18 with isogenic capsule disruptant mutant GAS-M18<sub>hasko</sub> (n = 8 mice/group). Data represent percentage of mice shedding each strain for 21 days following intra-nasal challenge (LogRank; ** = p<0.01).</p>", "links"=>[], "tags"=>["m18", "hyper-encapsulation", "phenotype", "mediates", "enhanced", "nasopharyngeal", "carriage"], "article_id"=>882554, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serotype_M18_GAS_display_a_unique_hyper_encapsulation_phenotype_which_mediates_enhanced_nasopharyngeal_carriage_longevity_/882554", "title"=>"Serotype M18 GAS display a unique hyper-encapsulation phenotype which mediates enhanced nasopharyngeal carriage longevity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323263"], "description"=>"<p>RocA and CovR sequence comparison of isolates representing major GAS serotypes. Strains sequenced from each serotype are outlined in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003842#ppat-1003842-t001\" target=\"_blank\">Table 1</a>; at least one clinical isolate was tested for each serotype. Ten serotype M18 strains were sequenced including two obtained from patients in 1934. (A) <i>rocA</i> gene sequence of different M types. Codons are shown by alternating bold text. The premature stop codon in <i>rocA</i><sub>M18</sub> is highlighted by red font. (B) The subsequent truncation in RocA<sub>M18</sub> protein is demonstrated schematically in comparison with RocA<sub>M89</sub>. (C) CovR amino acid sequence in different M types. Highlighted residues indicate amino acid change in the M18 CovR protein resulting from non-synonymous mutations in the gene sequence compared with other M types. RocA and CovR sequences were also evaluated from genome sequenced isolates submitted to NCBI, representing serotypes M1, M2, M3, M4, M5, M6, M12, M18, M28 and M49.</p>", "links"=>[], "tags"=>["serotype", "m18", "mutations", "regulators", "roca"], "article_id"=>882556, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_unique_serotype_M18_specific_mutations_in_regulators_RocA_and_CovR_/882556", "title"=>"Identification of unique serotype M18 specific mutations in regulators RocA and CovR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323264"], "description"=>"<p>Analysis of GAS-M18 strains over-expressing <i>rocA</i><sub>M89</sub>, <i>rocA</i><sub>M18</sub> and <i>covR</i><sub>M89</sub>. (A) Absolute copy number of <i>hasA</i> transcripts quantified relative to housekeeping gene <i>gyrA</i>. Data shown from mid-logarithmic (ML) growth phase. (B) Capsular HA production was quantified at ML by ELISA. Data represent mean and standard deviation of three independent experiments measured in triplicate (ANOVA with Bonferroni pairwise comparison;* = p<0.05, ** = p<0.01, *** = p<0.001).</p>", "links"=>[], "tags"=>["serotype", "m18"], "article_id"=>882557, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Over_expression_of_RocA_M89_but_not_CovR_M89_is_sufficient_to_reverse_serotype_M18_hyper_encapsulation_/882557", "title"=>"Over-expression of RocA<sub>M89</sub> but not CovR<sub>M89</sub> is sufficient to reverse serotype M18 hyper-encapsulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323265"], "description"=>"<p>Correction of the <i>rocA</i><sub>M18</sub> premature stop codon was achieved by allelic exchange of chromosomal <i>rocA</i><sub>M18</sub> with <i>rocA</i><sub>M89</sub> using suicide vector pUCMUT <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003842#ppat.1003842-Sriskandan1\" target=\"_blank\">[46]</a>. Double recombination events between <i>rocA</i> (<i>spy1614</i>) and 500 bp region of downstream gDNA including the 3′ end of <i>spy1611</i> resulted in replacement of <i>rocA</i><sub>M18</sub> with a single copy of <i>rocA</i><sub>M89</sub>, producing isogenic strain GAS-M18<sub>rocAM89</sub>. Allelic exchange was confirmed by PCR and sequencing.</p>", "links"=>[], "tags"=>["mutagenesis"], "article_id"=>882558, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Allelic_exchange_mutagenesis_of_rocA_M18_with_rocA_M89_in_GAS_M18_/882558", "title"=>"Allelic exchange mutagenesis of <i>rocA</i><sub>M18</sub> with <i>rocA</i><sub>M89</sub> in GAS-M18.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323266"], "description"=>"<p>(A–C) Analysis of the impact of single gene replacement of <i>rocA</i><sub>M89</sub> with <i>rocA</i><sub>M18</sub> in strain GAS-M89. (A) Absolute copy number of <i>hasA</i> transcripts quantified at early logarithmic (EL) growth phase relative to housekeeping gene <i>gyrA</i>. (B) Capsular HA production was quantified at ML. (C) Lancefield assay for quantification of GAS survival in whole human blood. (D–F) Analysis of the impact of single gene replacement of <i>rocA</i><sub>M18</sub> with <i>rocA</i><sub>M89</sub> in hyper-encapsulated GAS-M18. (D) Absolute copy number of <i>hasA</i> transcripts quantified at EL growth phase relative to housekeeping gene <i>gyrA</i>. (E) Capsular HA production was quantified at ML growth phase. (F) Lancefield Assay for quantification of GAS survival in whole human blood. Data represent mean and standard deviation for three independent experiments measured in triplicate (Unpaired t-test;* = p<0.05, ** = p<0.01, *** = p<0.001).</p>", "links"=>[], "tags"=>["truncation"], "article_id"=>882559, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RocA_M18_truncation_is_necessary_and_sufficient_for_hyper_encapsulation_/882559", "title"=>"RocA<sub>M18</sub> truncation is necessary and sufficient for hyper-encapsulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323267"], "description"=>"<p>RT-PCR analysis of isogenic strains GAS-M18 and GAS-M18<sub>rocAM89</sub> to ascertain the impact of RocA on expression of global regulator CovR. Quantification of absolute copy number of (A) <i>covR</i>, (B) <i>covS</i> and (C) <i>spyCEP</i> transcripts relative to housekeeping gene <i>gyrA</i> at EL growth phase. Data represent mean and standard deviation for three independent experiments measured in triplicate (un-paired t-test, * = p<0.05).</p>", "links"=>[], "tags"=>["roca", "transcript"], "article_id"=>882560, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_RocA_enhances_covR_but_not_covS_transcript_levels_/882560", "title"=>"Functional RocA enhances <i>covR</i> but not <i>covS</i> transcript levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323269"], "description"=>"<p>The impact of expressing full-length RocA<sub>M89</sub> on the GAS-M18 proteome was ascertained by quantitative SDS-PAGE LC-MS/MS using cell pellets obtained from 4 independent cultures of isogenic strains GAS-M18 and GAS-M18<sub>rocAM89</sub>. Values represent relative protein abundance (fold-change) in strain GAS-M18<sub>rocAM89</sub> relative to parent strain GAS-M18. Pink shading highlights genes included in the CovR/S regulon. Only proteins with altered expression of >1.5 fold and p≤0.05 were included. Numbers on x-axis represent M18 strain MGAS8232 ORFs.</p>", "links"=>[], "tags"=>["targeted", "proteome"], "article_id"=>882562, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RocA_has_targeted_impact_on_GAS_proteome_that_is_distinct_from_the_CovR_S_regulon_/882562", "title"=>"RocA has targeted impact on GAS proteome that is distinct from the CovR/S regulon.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323270"], "description"=>"<p>Imaging of serotype M18 strains (A) GAS-M18, (B) GAS-M18<sub>rocAM89</sub> and (C) GAS-M18<sub>hasko</sub> following overnight culture on Todd-Hewitt agar. i) Macroscopic imaging. ii)–iv)Scanning EM performed on individual colonies, each one imaged at three magnifications: ii) 3 k (white line = 2 µm), iii) 10 k (white line = 1 µm) and iv) 35 k (white line = 0.5 µm) respectively.</p>", "links"=>[], "tags"=>["capsule", "synthesis", "modulates", "bacterial"], "article_id"=>882563, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RocA_regulation_of_capsule_synthesis_modulates_bacterial_colony_structure_/882563", "title"=>"RocA regulation of capsule synthesis modulates bacterial colony structure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323271"], "description"=>"<p>(A) Quantification of murine nasopharyngeal carriage longevity of isogenic GAS strains GAS-M18, GAS-M18<sub>hasKO</sub> and GAS-M18<sub>rocAM89</sub> by nose-pressing (n = 8/group). Data represent percentage of mice colonized with each strain for 21 days following intra-nasal challenge (LogRank; *** = p<0.001). (B) Quantification of bacterial shedding as mean number of GAS cfu recovered from the mouse nasopharynx by daily nose-pressing onto individual blood agar plates (AUC and Kruskal Wallis (p<0.05)). (C) Quantification of airborne transmission of GAS to settle plates during the first 3 days of infection (n = 4 plates/cage) (AUC and Kruskal-Wallis; * = p<0.05).</p>", "links"=>[], "tags"=>["nasopharyngeal", "carriage", "longevity", "airborne", "hyper-encapsulation", "induced", "roca"], "article_id"=>882564, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GAS_M18_nasopharyngeal_carriage_longevity_and_airborne_spread_require_hyper_encapsulation_induced_by_RocA_truncation_/882564", "title"=>"GAS-M18 nasopharyngeal carriage longevity and airborne spread require hyper-encapsulation induced by RocA truncation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323272"], "description"=>"<p>CovR (black circle) is phosphorylated directly by CovS (blue ellipse), which induces CovR dimerization (green circles) and transcriptional repression of <i>hasA</i> and <i>spyCEP</i>, as well as auto-repression of <i>covR</i>. RocA (red ellipse) regulates expression of a number of gene products (solid red lines). RocA promotes transcription of <i>covR</i> potentially via an intermediate regulator (red dashed circle). RocA also promotes expression of proteins that are not part of the CovR regulon, whilst inhibiting many others. Such regulation may also require kinase action and an intermediate regulator.</p>", "links"=>[], "tags"=>["roca", "mediated"], "article_id"=>882565, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.g010"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proposed_mechanism_of_RocA_mediated_activity_/882565", "title"=>"Proposed mechanism of RocA mediated activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323273"], "description"=>"<p>Isogenic strains used in this study.</p>", "links"=>[], "tags"=>["strains"], "article_id"=>882566, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Isogenic_strains_used_in_this_study_/882566", "title"=>"Isogenic strains used in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323274"], "description"=>"<p>All strains were used for <i>in vitro</i> capsule quantification and <i>hasA</i> and <i>covRS</i> transcription assays except those in italics. Strains H566 and H293 are referred to in the text as GAS-M18 and GAS-M89 respectively.</p>*<p>denotes isolates from 1934;</p>c<p>denotes strains that underwent <i>covR/S</i> sequencing;</p>r<p>denotes strains that underwent <i>rocA</i> sequencing;</p>#<p>denotes strains used in mouse nasopharyngeal carriage experiments</p>", "links"=>[], "tags"=>["isolates"], "article_id"=>882567, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_isolates_used_in_this_study_/882567", "title"=>"Clinical isolates used in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-12-19 03:53:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1323275", "https://ndownloader.figshare.com/files/1323276", "https://ndownloader.figshare.com/files/1323277"], "description"=>"<div><p>Group A streptococcal isolates of serotype M18 are historically associated with epidemic waves of pharyngitis and the non-suppurative immune sequela rheumatic fever. The serotype is defined by a unique, highly encapsulated phenotype, yet the molecular basis for this unusual colony morphology is unknown. Here we identify a truncation in the regulatory protein RocA, unique to and conserved within our serotype M18 GAS collection, and demonstrate that it underlies the characteristic M18 capsule phenotype. Reciprocal allelic exchange mutagenesis of <i>rocA</i> between M18 GAS and M89 GAS demonstrated that truncation of RocA was both necessary and sufficient for hyper-encapsulation via up-regulation of both precursors required for hyaluronic acid synthesis. Although RocA was shown to positively enhance <i>covR</i> transcription, quantitative proteomics revealed RocA to be a metabolic regulator with activity beyond the CovR/S regulon. M18 GAS demonstrated a uniquely protuberant chain formation following culture on agar that was dependent on excess capsule and the RocA mutation. Correction of the M18 <i>rocA</i> mutation reduced GAS survival in human blood, and <i>in vivo</i> naso-pharyngeal carriage longevity in a murine model, with an associated drop in bacterial airborne transmission during infection. In summary, a naturally occurring truncation in a regulator explains the encapsulation phenotype, carriage longevity and transmissibility of M18 GAS, highlighting the close interrelation of metabolism, capsule and virulence.</p></div>", "links"=>[], "tags"=>["truncation", "underpins", "carriage", "longevity", "transmissibility", "serotype", "m18"], "article_id"=>882568, "categories"=>["Biological Sciences"], "users"=>["Nicola N. Lynskey", "David Goulding", "Magdalena Gierula", "Claire E. Turner", "Gordon Dougan", "Robert J. Edwards", "Shiranee Sriskandan"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003842.s001", "https://dx.doi.org/10.1371/journal.ppat.1003842.s002", "https://dx.doi.org/10.1371/journal.ppat.1003842.s003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RocA_Truncation_Underpins_Hyper_Encapsulation_Carriage_Longevity_and_Transmissibility_of_Serotype_M18_Group_A_Streptococci_/882568", "title"=>"RocA Truncation Underpins Hyper-Encapsulation, Carriage Longevity and Transmissibility of Serotype M18 Group A Streptococci", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-12-19 03:53:38"}

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Relative Metric

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