Castanea sativa (European Chestnut) Leaf Extracts Rich in Ursene and Oleanene Derivatives Block Staphylococcus aureus Virulence and Pathogenesis without Detectable Resistance
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{"title"=>"Castanea sativa (European Chestnut) leaf extracts rich in ursene and oleanene derivatives block Staphylococcus aureus virulence and pathogenesis without detectable resistance", "type"=>"journal", "authors"=>[{"first_name"=>"Cassandra L.", "last_name"=>"Quave", "scopus_author_id"=>"6507287129"}, {"first_name"=>"James T.", "last_name"=>"Lyles", "scopus_author_id"=>"36730605900"}, {"first_name"=>"Jeffery S.", "last_name"=>"Kavanaugh", "scopus_author_id"=>"7004925449"}, {"first_name"=>"Kate", "last_name"=>"Nelson", "scopus_author_id"=>"26656830800"}, {"first_name"=>"Corey P.", "last_name"=>"Parlet", "scopus_author_id"=>"55801310900"}, {"first_name"=>"Heidi A.", "last_name"=>"Crosby", "scopus_author_id"=>"8731426300"}, {"first_name"=>"Kristopher P.", "last_name"=>"Heilmann", "scopus_author_id"=>"35612284900"}, {"first_name"=>"Alexander R.", "last_name"=>"Horswill", "scopus_author_id"=>"6603536558"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84942915722", "pui"=>"606195401", "doi"=>"10.1371/journal.pone.0136486", "isbn"=>"5871204090", "sgr"=>"84942915722", "pmid"=>"26295163"}, "id"=>"81efb4a0-ca61-33b2-98f3-29a02a1aaf03", "abstract"=>"The Mediterranean is home to a rich history of medical traditions that have developed under the influence of diverse cultures over millennia. Today, many such traditions are still alive in the folk medical practices of local people. Investigation of botanical folk medicines used in the treatment of skin and soft tissue infections led us to study Castanea sativa (European Chestnut) for its potential antibacterial activity. Here, we report the quorum sensing inhibi- tory activity of refined and chemically characterized European Chestnut leaf extracts, rich in oleanene and ursene derivatives (pentacyclic triterpenes), against all Staphylococcus aureus accessory gene regulator (agr) alleles.Wepresent layers of evidence of agr blocking activity (IC50 1.56–25 μgmL-1), as measured in toxin outputs, reporter assays hemolytic activity, cytotoxicity studies, and an in vivo abscessmodel. Wedemonstrate the extract’s lack of cytotoxicity to human keratinocytes and murine skin, as well as lack of growth inhibi- tory activity against S. aureus and a panel of skin commensals. Lastly, we demonstrate that serial passaging of the extract does not result in acquisition of resistance to the quorum quenching composition. In conclusion, through disruption of quorum sensing in the absence of growth inhibition, this study provides insight into the role that non-biocide inhibitors of vir- ulence may play in future antibiotic therapies.", "link"=>"http://www.mendeley.com/research/castanea-sativa-european-chestnut-leaf-extracts-rich-ursene-oleanene-derivatives-block-staphylococcu", "reader_count"=>33, "reader_count_by_academic_status"=>{"Researcher"=>5, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Other"=>2, "Student > Master"=>8, "Student > Bachelor"=>2, "Professor"=>1, "Professor > Associate Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>5, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Other"=>2, "Student > Master"=>8, "Student > Bachelor"=>2, "Professor"=>1, "Professor > Associate Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>21, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Chemistry"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>21}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"Turkey"=>1, "Iran"=>1, "Chile"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2220420"], "description"=>"<p>Compounds are listed by Peak number, corresponding to <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.t005\" target=\"_blank\">Table 5</a>. Peak <b>32</b> was determined to be C<sub>35</sub>H<sub>59</sub>O<sub>6</sub> with a relative abundance of 0.30%. Putative structural matches include: (<b>32a</b>) stigmastane and (<b>32b</b>) (3β, 4β, 16α, 21β, 22α) -16, 21, 22, 23, 28- pentamethoxy (9CI) olean- 12- en- 3- ol (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.g010\" target=\"_blank\">Fig 10</a>). Peak <b>33</b> was determined to be C<sub>27</sub>H<sub>23</sub>O<sub>18</sub> with a relative abundance of 0.16%. Putative structural matches include: (<b>33a</b>) 1,3,6-tri-O-galloylglucose; (<b>33b</b>) 1,2,6-tri-galloyl-β-D-glucose; (<b>33c</b>) 1,2,3-tri-O-galloylglucose; (<b>33d</b>) 1,2,3-tri-O-galloyl-β-D-glucopyranose; (<b>33e</b>) 2',3,5-tri-O-galloyl-D-hamamelose; (<b>33f</b>) 2- <i>C</i>- [[(3, 4, 5- trihydroxybenzoyl) oxy] methyl]- 1, 5- bis(3, 4, 5- trihydroxybenzoate) D- Ribofuranose; (<b>33g</b>) kurigalin; (<b>33h</b>) 3,4,6-tri-O-galloyl-D-glucose. Peak <b>34</b> was determined to be C<sub>39</sub>H<sub>31</sub>O<sub>15</sub> with a relative abundance of 0.65%. Putative structural matches include: (<b>34</b>) castanoside B. Peak <b>39</b> was determined to be C<sub>17</sub>H<sub>11</sub>O<sub>8</sub> or C<sub>20</sub>H<sub>11</sub>O<sub>4</sub>N<sub>2</sub> with a relative abundance of 0.72%. Putative structural matches include: (<b>39a</b>) 3,4,3'-tri-O-methylellagic acid and (<b>39b</b>) 3,3',4'-tri-O-methylellagic acid. Peak <b>44</b> was determined to be C<sub>34</sub>H<sub>29</sub>O<sub>15</sub> with a relative abundance of 0.26%. Putative structural matches included (<b>44</b>) norbadione A.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516621, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g011", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Putative_structures_of_compounds_other_than_pentacyclic_triterpenes_found_in_the_most_active_region_of_224C_F2_retention_time_of_21_8211_49_min_/1516621", "title"=>"Putative structures of compounds other than pentacyclic triterpenes found in the most active region of 224C-F2 (retention time of 21–49 min).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220396"], "description"=>"<p><b>(A)</b> The bioassay-guided fractionation scheme is illustrated, demonstrating the path from raw plant material to isolated, active natural products. (<b>B)</b> The corresponding HPLC chromatogram for the most active fractions illustrates how fractionation functions to increase the relative levels of active agents.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516603, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Isolation_scheme_/1516603", "title"=>"Isolation scheme.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220419"], "description"=>"<p>Compounds are listed by Peak number, corresponding to <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.t005\" target=\"_blank\">Table 5</a>. Peak <b>31</b> was determined to be C<sub>39</sub>H<sub>59</sub>O<sub>8</sub> or C<sub>38</sub>H<sub>55</sub>O<sub>9</sub> with a relative abundance of 0.34%. Putative structural matches include: (<b>31a</b>) escigenin tetraacetate (6CI); (<b>31b</b>) tetraacetate (7CI, 8CI) 16α, 21α- epoxy-olean- 9(11)—ene- 3β, 22β, 24, 28- tetrol; (<b>31c</b>) tetraacetate aescigenin; (<b>31d</b>) triacetate (8CI) cyclic 16, 22- acetal-olean- 12- ene- 3β, 16α, 21β, 22α, 28- pentol; (<b>31e</b>) triacetate (8CI) cyclic 22, 28- acetal-olean- 12- ene- 3β, 16α, 21β, 22α, 28- pentol. Peak <b>32</b> was determined to be C<sub>35</sub>H<sub>59</sub>O<sub>6</sub> with a relative abundance of 0.30%. Putative structural matches include: (<b>32a</b>) stigmastane (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.g011\" target=\"_blank\">Fig 11</a>) and (<b>32b</b>) (3β, 4β, 16α, 21β, 22α) -16, 21, 22, 23, 28- pentamethoxy (9CI) olean- 12- en- 3- ol. Peak <b>42</b> was determined to be C<sub>31</sub>H<sub>49</sub>O<sub>6</sub> with a relative abundance of 1.43%. Putative structural matches included (<b>42</b>) amirinic acid. Peak <b>52</b> was determined to be C<sub>32</sub>H<sub>51</sub>O<sub>7</sub> with a relative abundance of 0.48%. Putative structural matches include: (<b>52a</b>) 21-acetate protoescigenin, (<b>52b</b>) 16-acetate protoescigenin, (<b>52c</b>) 22-acetate protoescigenin and (<b>52d</b>) 28-acetate protoescigenin. Peak <b>55</b> was determined to be C<sub>30</sub>H<sub>48</sub>O<sub>5</sub>, with a relative abundance of 4.11%. Putative structural matches include: (<b>55a</b>) 16,21-epoxy-(3β,4β,16α,21α,22β)-olean-12-ene-3,22,24,28-tetrol (9CI); (<b>55b</b>) asiatic acid; (<b>55c</b>) arjunolic acid; (<b>55d</b>) isoescigenin. Peak <b>60</b> was determined to be C<sub>30</sub>H<sub>48</sub>O<sub>6</sub>, with a relative abundance of 6.80%. Putative structural matches include: (<b>60a</b>) camelliagenin E; (<b>60b</b>) brahmic acid; (<b>60c</b>) sericic acid; (<b>60d</b>) belleric acid; and (<b>60e</b>) 2,3,23,24-tetrahydroxy-(2α,3β)-urs-12-en-28-oic acid. Peak <b>64</b> was determined to be C<sub>30</sub>H<sub>45</sub>O<sub>5</sub>, with a relative abundance of 2.91%. The putative structural match is (<b>64</b>) ouillaic acid.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516620, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g010", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Putative_structures_of_ursene_and_oleanene_derivatives_found_in_the_most_active_region_of_224C_F2_retention_time_of_21_8211_49_min_were_determined_following_MS_analysis_and_database_searches_/1516620", "title"=>"Putative structures of ursene and oleanene derivatives found in the most active region of 224C-F2 (retention time of 21–49 min) were determined following MS analysis and database searches.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220416"], "description"=>"<p><b>(A)</b> Immortalized human keratinocytes (HaCaT cells) were treated with up to 512 μg mL<sup>-1</sup> of extract fractions (24 hrs). The LD<sub>50</sub> for 224C-F2 could not be determined at this test range, indicating that it is well above the active dose for quorum quenching activity (IC<sub>50</sub> = 1.56–25 μg mL<sup>-1</sup>, depending on strain). <b>(B)</b> Uninfected mice received an intradermal injection of 5 or 50 μg 224C-F2. No gross alterations in skin appearance were observed.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516617, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g007", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_224C_F2_is_non_toxic_to_human_keratinocytes_and_murine_skin_/1516617", "title"=>"224C-F2 is non-toxic to human keratinocytes and murine skin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220395"], "description"=>"<p>The <i>agr</i> locus has been investigated in detail and is known to contain two divergent transcripts named RNAII and RNAIII [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.ref009\" target=\"_blank\">9</a>]. The RNAII transcript is an operon of four genes, <i>agrBDCA</i>, that encode factors required to synthesize AIP and activate the regulatory cascade. Briefly, AgrD is the precursor peptide of AIP, AgrB is a membrane protease involved in generating AIP, AgrC is a histidine kinase that is activated by binding AIP, and AgrA is a response regulator that induces transcription of both RNAII and RNAIII. The RNAIII transcript yields a regulatory RNA molecule that acts as the primary effector of the <i>agr</i> system by up-regulating extracellular virulence factors and down-regulating cell surface proteins [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.ref065\" target=\"_blank\">65</a>]. The <i>agr</i> pathway is illustrated here with potential target sites for 224C-F2.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516602, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g001", "stats"=>{"downloads"=>0, "page_views"=>32, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_the_Staphylococcus_aureus_accessory_gene_regulator_system_/1516602", "title"=>"Schematic of the <i>Staphylococcus aureus</i> accessory gene regulator system.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220422"], "description"=>"<p><b>*<i>m/z</i>:</b> When multiple base ions were formed, the number in <b>bold font</b> indicates the ion that was used to predict empirical formula and underwent MS<sup>2</sup> fragmentation.</p><p>ND = not detected.</p><p>The corresponding chromatogram is reported in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.g009\" target=\"_blank\">Fig 9</a>; putative structures in Figs <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.g010\" target=\"_blank\">10</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.g011\" target=\"_blank\">11</a>.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516623, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.t005", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mass_spectrometry_m_z_analysis_of_224C_F2_/1516623", "title"=>"Mass spectrometry (m/z) analysis of 224C-F2.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220398"], "description"=>"<p><i>S</i>. <i>aureus agr</i> reporter strains were treated with extracts 224, 224C, and 224C-F2 at a dose range of 0.05–100 μg mL<sup>-1</sup>. Bioactivity guided sequential fractionation resulted in increased quenching of all 4 <i>agr</i> alleles in a manner independent of growth inhibition. Optical density of the culture is represented by solid black symbols; fluorescence in the <i>agr</i> reporters is indicated by the open symbols. The IC<sub>50</sub> and IC<sub>90</sub> for quorum quenching impact of each extract are reported in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.t003\" target=\"_blank\">Table 3</a>. <b>(A)</b> agr I, AH1677; <b>(B)</b> agr II, AH430; <b>(C)</b> agr III, AH1747; <b>(D)</b> agr IV, AH1872.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516605, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_European_Chestnut_leaf_extracts_inhibit_all_four_S_aureus_agr_alleles_a_non_biocide_manner_/1516605", "title"=>"European Chestnut leaf extracts inhibit all four <i>S</i>. <i>aureus agr</i> alleles a non-biocide manner.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220421"], "description"=>"<p><b>*Other Characteristics:</b> agr: accessory gene regulator; CA-MRSA: community-associated methicillin resistant <i>Staphylococcus aureus</i>; HA-MRSA: healthcare-associated MRSA; HMP: Human Microbiome Project isolate; PFT: pulsed field type; MLST: multilocus sequence type; MSSA: methicillin sensitive <i>Staphylococcus</i> aureus; SCC: staphylococcal chromosomal cassette; sea: staphylococcal enterotoxin A; seb: staphylococcal enterotoxin B; ST: sequence type; yfp: yellow fluorescent protein.</p><p>Description of bacterial strains and plasmids used in this study.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516622, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.t001", "stats"=>{"downloads"=>7, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Description_of_bacterial_strains_and_plasmids_used_in_this_study_/1516622", "title"=>"Description of bacterial strains and plasmids used in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220418"], "description"=>"<p>All peaks correspond to data presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.t005\" target=\"_blank\">Table 5</a>. Putative structures are reported in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136486#pone.0136486.g010\" target=\"_blank\">Fig 10</a>.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516619, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g009", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LC_FTMS_ESI_negative_base_peak_chromatogram_for_224C_F2_/1516619", "title"=>"LC-FTMS ESI negative base peak chromatogram for 224C-F2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220417"], "description"=>"<p>C5Bl/6 mice were intradermally injected with 1x10<sup>8</sup> CFUs of LAC (USA 300 isolate, AH1263) or its <i>agr</i> deletion mutant (AH1292). Mice received a single dose of 224C-F2 (at 5 or 50 μg) or the vehicle control (DMSO) at the time of infection. Significant differences between treatment and vehicle are represented as: *: p<0.05; ‡: p<0.01. <b>(A)</b> Images of abscesses and ulcers on days 2 and 6 post-infection (scale in cm). <b>(B)</b> 224C-F2 attenuates dermatopathology with a single dose of either 5 or 50 μg. <b>(C)</b> 224C-F2 reduces morbidity and mice do not lose weight.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516618, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g008", "stats"=>{"downloads"=>3, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_224C_F2_attenuates_MRSA_induced_dermatopathology_in_a_murine_model_of_skin_and_soft_tissue_infection_/1516618", "title"=>"224C-F2 attenuates MRSA-induced dermatopathology in a murine model of skin and soft tissue infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220411"], "description"=>"<p>Cultures of USA500 isolate NRS385 (<i>agr</i> group I) were passaged for 15 consecutive days in the presence of 16 μg mL<sup>-1</sup> of 224C-F2. <b>(A)</b> The sum total peak area of de-formylated and formylated delta toxin was quantified for the mock vehicle control (DMSO) and treated group. A significant difference (p<0.05) was evident for all treatment days. <b>(B)</b> 224C-F2 inhibited delta-toxin production over the length of the passaging experiment in the absence of growth inhibition. Significant differences between treatment and vehicle are represented as: *: <i>p</i><0.05; ‡: <i>p</i><0.01; †: <i>p</i><0.001.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516612, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g006", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_224C_F2_attenuates_virulence_without_any_detectable_resistance_after_15_days_of_drug_passaging_/1516612", "title"=>"224C-F2 attenuates virulence without any detectable resistance after 15 days of drug passaging.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220408"], "description"=>"<p><b>(A)</b> Supernatants were applied to HaCaT cells (20% v/v for 24 hrs) to measure the lytic capacity (determined by LDH assay) of a full suite of <i>S</i>. <i>aureus</i> exotoxins. Supernatants from 224C-F2-treated cultures were non-toxic to the mammalian cells, confirming inhibition of exotoxin production. <b>(B)</b> Following exposure to supernatants (14% v/v for 3 hrs) or staurosporine (7.1 μM for 3 hrs), HaCaT cells were imaged by fluorescent microscopy to examine cell integrity. Green cells are live, red are dead. Black regions are indicative of dead cells that have detached from the slide. Significant differences between treatment and vehicle are represented as: *: <i>p</i><0.05; ‡: <i>p</i><0.01; †: <i>p</i><0.001.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516609, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spent_supernatants_of_S_aureus_treated_with_224C_F2_exhibit_diminished_cytotoxic_effects_against_human_keratinocytes_/1516609", "title"=>"Spent supernatants of <i>S</i>. <i>aureus</i> treated with 224C-F2 exhibit diminished cytotoxic effects against human keratinocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/2220406"], "description"=>"<p><b>(A)</b> 224C-F2 demonstrates a dose-dependent effect in inhibition of de-formylated and formylated delta toxin, as illustrated in this HPLC chromatogram. <b>(B)</b> Quantification of delta-toxin confirmed the dose-dependent inhibitory activity of extracts, and the increased activity of the refined fraction 224C-F2 over 224 and 224C. <b>(C)</b> Extracts quench the hemolytic activity of both the <i>S</i>. <i>aureus</i> wild type and Δ<i>hla</i> mutant, demonstrating that in addition to preventing production of α-hemolysin (responsible for the major share of hemolytic activity), that extracts also inhibit PSM production, responsible for the observable hemolytic activity in <i>hla</i> mutant strains. All treated groups are significant in comparison to the vehicle control (<i>p</i><0.001). <b>(D)</b> USA300 (Δ<i>spa</i>) was exposed to increasing doses of 224, 224C, 224C-F2, and vehicle control for 8 hrs. Western blot for α-hemolysin on supernatants demonstrated a dose-dependent decline in protein levels. Significant differences between treatment and vehicle are represented as: *: <i>p</i><0.05; ‡: <i>p</i><0.01; †: <i>p</i><0.001.</p>", "links"=>[], "tags"=>["lack", "quorum quenching composition", "folk", "Oleanene Derivatives Block Staphylococcus aureus Virulence", "European Chestnut leaf extracts", "future antibiotic therapies", "Staphylococcus aureus accessory gene regulator", "European Chestnut", "Leaf Extracts Rich", "vivo abscess model", "ic", "tradition", "cytotoxicity", "study Castanea sativa", "agr"], "article_id"=>1516607, "categories"=>["Biological Sciences", "Ecology"], "users"=>["Cassandra L. Quave", "James T. Lyles", "Jeffery S. Kavanaugh", "Kate Nelson", "Corey P. Parlet", "Heidi A. Crosby", "Kristopher P. Heilmann", "Alexander R. Horswill"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0136486.g004", "stats"=>{"downloads"=>11, "page_views"=>38, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_224C_F2_blocks_MRSA_exotoxin_production_/1516607", "title"=>"224C-F2 blocks MRSA exotoxin production.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-21 03:34:44"}

PMC Usage Stats | Further Information

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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