{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:28:31Z","timestamp":1781105311343,"version":"3.54.1"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,1,12]]},"abstract":"<jats:p>\n                    Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    genome that is epidemiologically associated with decreased human necrotizing fasciitis (\u201cflesh-eating disease\u201d). Working from this clinical observation, we find that wild-type\n                    <jats:italic>mtsR<\/jats:italic>\n                    function is required for group A\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that\n                    <jats:italic>mtsR<\/jats:italic>\n                    inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress\n                    <jats:italic>prsA<\/jats:italic>\n                    or lack\n                    <jats:italic>speB<\/jats:italic>\n                    had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the \u0394\n                    <jats:italic>mtsR<\/jats:italic>\n                    mutant strain in mice and monkeys.\n                    <jats:italic>mtsR<\/jats:italic>\n                    inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0911811107","type":"journal-article","created":{"date-parts":[[2010,1,4]],"date-time":"2010-01-04T21:36:36Z","timestamp":1262640996000},"page":"888-893","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":97,"title":["Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis"],"prefix":"10.1073","volume":"107","author":[{"given":"Randall J.","family":"Olsen","sequence":"first","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Sitkiewicz","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ara A.","family":"Ayeras","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vedia E.","family":"Gonulal","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepcion","family":"Cantu","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Beres","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Green","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benfang","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Humbird","sequence":"additional","affiliation":[{"name":"Animal Care Operations, University of Houston, Houston, TX 77204;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamieson","family":"Greaver","sequence":"additional","affiliation":[{"name":"Animal Care Operations, University of Houston, Houston, TX 77204;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willie P.","family":"Ragasa","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"ComPath, Jay, OK 74346;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Joiner","family":"Cartwright","sequence":"additional","affiliation":[{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"McGeer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald E.","family":"Low","sequence":"additional","affiliation":[{"name":"Ontario Agency for Health Protection and Promotion, and University of Toronto, Toronto, ON M5S 1A1; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline R.","family":"Whitney","sequence":"additional","affiliation":[{"name":"Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip T.","family":"Cagle","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry L.","family":"Blasdel","sequence":"additional","affiliation":[{"name":"Animal Care Operations, University of Houston, Houston, TX 77204;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank R.","family":"DeLeo","sequence":"additional","affiliation":[{"name":"Ontario Agency for Health Protection and Promotion, and University of Toronto, Toronto, ON M5S 1A1; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Musser","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Disease Research, The Methodist Hospital Research Institute, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,1,4]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"e800","DOI":"10.1371\/journal.pone.0000800","article-title":"Contribution of exogenous genetic elements to the group A Streptococcus metagenome","volume":"2","author":"Beres SB","year":"2007","unstructured":"SB Beres, JM Musser, Contribution of exogenous genetic elements to the group A Streptococcus metagenome. PLoS One 2, e800 (2007).","journal-title":"PLoS One"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/nature06742","article-title":"Genotype, haplotype and copy-number variation in worldwide human populations","volume":"451","author":"Jakobsson M","year":"2008","unstructured":"M Jakobsson, et al., Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451, 998\u20131003 (2008).","journal-title":"Nature"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"7059","DOI":"10.1073\/pnas.0510279103","article-title":"Molecular genetic anatomy of inter- and intraserotype variation in the human bacterial pathogen group A Streptococcus","volume":"103","author":"Beres SB","year":"2006","unstructured":"SB Beres, et al., Molecular genetic anatomy of inter- and intraserotype variation in the human bacterial pathogen group A Streptococcus. Proc Natl Acad Sci USA 103, 7059\u20137064 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"11833","DOI":"10.1073\/pnas.0404163101","article-title":"Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections","volume":"101","author":"Beres SB","year":"2004","unstructured":"SB Beres, et al., Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections. Proc Natl Acad Sci USA 101, 11833\u201311838 (2004).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1172\/JCI38095","article-title":"A decade of molecular pathogenomic analysis of group A Streptococcus","volume":"119","author":"Musser JM","year":"2009","unstructured":"JM Musser, SA Shelburne, A decade of molecular pathogenomic analysis of group A Streptococcus. J Clin Invest 119, 2455\u20132463 (2009).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1056\/NEJM199608223350803","article-title":"Invasive group A streptococcal infections in Ontario, Canada","volume":"335","author":"Davies HD","year":"1996","unstructured":"HD Davies, et al., Invasive group A streptococcal infections in Ontario, Canada. N Engl J Med 335, 547\u2013554 (1996).","journal-title":"N Engl J Med"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1086\/338466","article-title":"Severe group a streptococcal soft-tissue infections in Ontario: 1992-1996","volume":"34","author":"Sharkawy A","year":"2002","unstructured":"A Sharkawy, et al., Severe group a streptococcal soft-tissue infections in Ontario: 1992-1996. Clin Infect Dis 34, 454\u2013460 (2002).","journal-title":"Clin Infect Dis"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"5743","DOI":"10.1128\/IAI.73.9.5743-5753.2005","article-title":"Characterization of MtsR, a new metal regulator in group A streptococcus, involved in iron acquisition and virulence","volume":"73","author":"Bates CS","year":"2005","unstructured":"CS Bates, C Toukoki, MN Neely, Z Eichenbaum, Characterization of MtsR, a new metal regulator in group A streptococcus, involved in iron acquisition and virulence. Infect Immun 73, 5743\u20135753 (2005).","journal-title":"Infect Immun"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"5132","DOI":"10.1128\/IAI.00176-06","article-title":"Differential regulation of iron- and manganese-specific MtsABC and heme-specific HtsABC transporters by the metalloregulator MtsR of group A Streptococcus","volume":"74","author":"Hanks TS","year":"2006","unstructured":"TS Hanks, et al., Differential regulation of iron- and manganese-specific MtsABC and heme-specific HtsABC transporters by the metalloregulator MtsR of group A Streptococcus. Infect Immun 74, 5132\u20135139 (2006).","journal-title":"Infect Immun"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"52789","DOI":"10.1074\/jbc.M410698200","article-title":"Insight of host immune evasion mediated by two variants of group a Streptococcus Mac protein","volume":"279","author":"Agniswamy J","year":"2004","unstructured":"J Agniswamy, B Lei, JM Musser, PD Sun, Insight of host immune evasion mediated by two variants of group a Streptococcus Mac protein. J Biol Chem 279, 52789\u201352796 (2004).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1128\/IAI.01354-07","article-title":"A chemokine-degrading extracellular protease made by group A Streptococcus alters pathogenesis by enhancing evasion of the innate immune response","volume":"76","author":"Sumby P","year":"2008","unstructured":"P Sumby, et al., A chemokine-degrading extracellular protease made by group A Streptococcus alters pathogenesis by enhancing evasion of the innate immune response. Infect Immun 76, 978\u2013985 (2008).","journal-title":"Infect Immun"},{"key":"e_1_3_4_12_2","first-page":"255","article-title":"A non-human primate model of acute group a Streptococcus pharyngitis","volume":"431","author":"Sumby P","year":"2008","unstructured":"P Sumby, AH Tart, JM Musser, A non-human primate model of acute group a Streptococcus pharyngitis. Methods Mol Biol 431, 255\u2013267 (2008).","journal-title":"Methods Mol Biol"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1086\/504261","article-title":"Group A streptococcal myonecrosis: Increased vimentin expression after skeletal-muscle injury mediates the binding of Streptococcus pyogenes","volume":"193","author":"Bryant AE","year":"2006","unstructured":"AE Bryant, CR Bayer, JD Huntington, DL Stevens, Group A streptococcal myonecrosis: Increased vimentin expression after skeletal-muscle injury mediates the binding of Streptococcus pyogenes. J Infect Dis 193, 1685\u20131692 (2006).","journal-title":"J Infect Dis"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1586\/14787210.3.2.279","article-title":"Necrotizing fasciitis: Pathogenesis and treatment","volume":"3","author":"Young MH","year":"2005","unstructured":"MH Young, DM Aronoff, NC Engleberg, Necrotizing fasciitis: Pathogenesis and treatment. Expert Rev Anti Infect Ther 3, 279\u2013294 (2005).","journal-title":"Expert Rev Anti Infect Ther"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"7626","DOI":"10.1128\/JB.01059-06","article-title":"Identification and characterization of bicistronic speB and prsA gene expression in the group A Streptococcus","volume":"188","author":"Ma Y","year":"2006","unstructured":"Y Ma, et al., Identification and characterization of bicistronic speB and prsA gene expression in the group A Streptococcus. J Bacteriol 188, 7626\u20137634 (2006).","journal-title":"J Bacteriol"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"3931","DOI":"10.1128\/IAI.66.8.3931-3935.1998","article-title":"Role of streptococcal pyrogenic exotoxin B in the mouse model of group A streptococcal infection","volume":"66","author":"Kuo CF","year":"1998","unstructured":"CF Kuo, et al., Role of streptococcal pyrogenic exotoxin B in the mouse model of group A streptococcal infection. Infect Immun 66, 3931\u20133935 (1998).","journal-title":"Infect Immun"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"4744","DOI":"10.1128\/iai.64.11.4744-4750.1996","article-title":"Activation of a 66-kilodalton human endothelial cell matrix metalloprotease by Streptococcus pyogenes extracellular cysteine protease","volume":"64","author":"Burns EH","year":"1996","unstructured":"EH Burns, AM Marciel, JM Musser, Activation of a 66-kilodalton human endothelial cell matrix metalloprotease by Streptococcus pyogenes extracellular cysteine protease. Infect Immun 64, 4744\u20134750 (1996).","journal-title":"Infect Immun"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1006\/mpat.1993.1083","article-title":"A conserved Streptococcus pyogenes extracellular cysteine protease cleaves human fibronectin and degrades vitronectin","volume":"15","author":"Kapur V","year":"1993","unstructured":"V Kapur, et al., A conserved Streptococcus pyogenes extracellular cysteine protease cleaves human fibronectin and degrades vitronectin. Microb Pathog 15, 327\u2013346 (1993).","journal-title":"Microb Pathog"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1128\/IAI.01116-07","article-title":"Degradation of complement 3 by streptococcal pyrogenic exotoxin B inhibits complement activation and neutrophil opsonophagocytosis","volume":"76","author":"Kuo CF","year":"2008","unstructured":"CF Kuo, YS Lin, WJ Chuang, JJ Wu, N Tsao, Degradation of complement 3 by streptococcal pyrogenic exotoxin B inhibits complement activation and neutrophil opsonophagocytosis. Infect Immun 76, 1163\u20131169 (2008).","journal-title":"Infect Immun"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1172\/JCI119445","article-title":"Inactivation of Streptococcus pyogenes extracellular cysteine protease significantly decreases mouse lethality of serotype M3 and M49 strains","volume":"99","author":"Lukomski S","year":"1997","unstructured":"S Lukomski, et al., Inactivation of Streptococcus pyogenes extracellular cysteine protease significantly decreases mouse lethality of serotype M3 and M49 strains. J Clin Invest 99, 2574\u20132580 (1997).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1046\/j.1365-2958.2000.02144.x","article-title":"Role for a secreted cysteine proteinase in the establishment of host tissue tropism by group A streptococci","volume":"38","author":"Svensson MD","year":"2000","unstructured":"MD Svensson, et al., Role for a secreted cysteine proteinase in the establishment of host tissue tropism by group A streptococci. Mol Microbiol 38, 242\u2013253 (2000).","journal-title":"Mol Microbiol"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"6253","DOI":"10.1074\/jbc.M704821200","article-title":"Group A streptococcal cysteine protease degrades C3 (C3b) and contributes to evasion of innate immunity","volume":"283","author":"Terao Y","year":"2008","unstructured":"Y Terao, et al., Group A streptococcal cysteine protease degrades C3 (C3b) and contributes to evasion of innate immunity. J Biol Chem 283, 6253\u20136260 (2008).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1128\/JB.180.11.2830-2835.1998","article-title":"Enhanced secretory production of a single-chain antibody fragment from Bacillus subtilis by coproduction of molecular chaperones","volume":"180","author":"Wu SC","year":"1998","unstructured":"SC Wu, R Ye, XC Wu, SC Ng, SL Wong, Enhanced secretory production of a single-chain antibody fragment from Bacillus subtilis by coproduction of molecular chaperones. J Bacteriol 180, 2830\u20132835 (1998).","journal-title":"J Bacteriol"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1128\/JB.183.6.1881-1890.2001","article-title":"Quantitation of the capacity of the secretion apparatus and requirement for PrsA in growth and secretion of alpha-amylase in Bacillus subtilis","volume":"183","author":"Vitikainen M","year":"2001","unstructured":"M Vitikainen, et al., Quantitation of the capacity of the secretion apparatus and requirement for PrsA in growth and secretion of alpha-amylase in Bacillus subtilis. J Bacteriol 183, 1881\u20131890 (2001).","journal-title":"J Bacteriol"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1365-2672.2005.02572.x","article-title":"Secretion of heterologous proteins in Bacillus subtilis can be improved by engineering cell components affecting post-translocational protein folding and degradation","volume":"99","author":"Vitikainen M","year":"2005","unstructured":"M Vitikainen, HL Hyyryl\u00e4inen, A Kivim\u00e4ki, VP Kontinen, M Sarvas, Secretion of heterologous proteins in Bacillus subtilis can be improved by engineering cell components affecting post-translocational protein folding and degradation. J Appl Microbiol 99, 363\u2013375 (2005).","journal-title":"J Appl Microbiol"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1128\/IAI.01392-07","article-title":"Cathelicidin LL-37 in severe Streptococcus pyogenes soft tissue infections in humans","volume":"76","author":"Johansson L","year":"2008","unstructured":"L Johansson, et al., Cathelicidin LL-37 in severe Streptococcus pyogenes soft tissue infections in humans. Infect Immun 76, 3399\u20133404 (2008).","journal-title":"Infect Immun"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1462-5822.2008.01225.x","article-title":"Molecular mechanisms underlying group A streptococcal pathogenesis","volume":"11","author":"Olsen RJ","year":"2009","unstructured":"RJ Olsen, SA Shelburne, JM Musser, Molecular mechanisms underlying group A streptococcal pathogenesis. Cell Microbiol 11, 1\u201312 (2009).","journal-title":"Cell Microbiol"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1073\/pnas.0710217105","article-title":"Epidemic community-associated methicillin-resistant Staphylococcus aureus: Recent clonal expansion and diversification","volume":"105","author":"Kennedy AD","year":"2008","unstructured":"AD Kennedy, et al., Epidemic community-associated methicillin-resistant Staphylococcus aureus: Recent clonal expansion and diversification. Proc Natl Acad Sci USA 105, 1327\u20131332 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"8487","DOI":"10.1073\/pnas.0602138103","article-title":"Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients","volume":"103","author":"Smith EE","year":"2006","unstructured":"EE Smith, et al., Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci USA 103, 8487\u20138492 (2006).","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0911811107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T02:51:02Z","timestamp":1654570262000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0911811107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1,4]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,1,12]]}},"alternative-id":["10.1073\/pnas.0911811107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0911811107","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1705956.1213054","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,1,4]]},"assertion":[{"value":"2010-01-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}