{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:45:08Z","timestamp":1762004708907},"reference-count":74,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2015,5,15]],"date-time":"2015-05-15T00:00:00Z","timestamp":1431648000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2015,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The polysaccharide capsule of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pneumoniae<\/jats:named-content>\n            is required for nasopharyngeal colonization and for invasive disease in the lungs, blood, and meninges. In contrast, the vast majority of conjunctival isolates are acapsular. The first serotype-specific gene in the capsule operon,\n            <jats:italic>cpsE<\/jats:italic>\n            , encodes the initiating glycosyltransferase and is one of the few serotype-specific genes that can tolerate null mutations. This report characterizes a spontaneously arising TIGR4 mutant exhibiting a reduced capsule, caused by a 6-nucleotide duplication in\n            <jats:italic>cpsE<\/jats:italic>\n            which results in duplication of Ala and Ile at positions 45 and 46. This strain (AI45dup) possessed more exposed phosphorylcholine and was hypersusceptible to C3 complement deposition compared to the wild type. Accordingly, the mutant was significantly better at forming abiotic biofilms and binding epithelial cells\n            <jats:italic>in vitro<\/jats:italic>\n            but was avirulent in a sepsis model.\n            <jats:italic>In vitro<\/jats:italic>\n            serial passaging of the wild-type strain failed to reproduce the AI45dup mutation but instead led to a variety of mutants with reduced capsule harboring single nucleotide polymorphisms (SNPs) in\n            <jats:italic>cpsE<\/jats:italic>\n            . A single passage in the sepsis model after high-dose inoculation readily yielded revertants of AI45dup with restored wild-type capsule level, but the majority of SNP alleles of\n            <jats:italic>cpsE<\/jats:italic>\n            could not revert, suppress, or bypass. Analysis of\n            <jats:italic>cpsE<\/jats:italic>\n            in conjunctival isolates revealed a strain with a single missense mutation at amino acid position 377, which was responsible for reduced encapsulation. This study supports the hypothesis that spontaneous, nonreverting mutations in\n            <jats:italic>cpsE<\/jats:italic>\n            serve as a form of adaptive mutation by providing a selective advantage to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. pneumoniae<\/jats:named-content>\n            in niches where expression of capsule is detrimental.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            While the capsule of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pneumoniae<\/jats:named-content>\n            is required for colonization and invasive disease, most conjunctival isolates are acapsular by virtue of deletion of the entire capsular operon. We show that spontaneous acapsular mutants isolated\n            <jats:italic>in vitro<\/jats:italic>\n            harbor mostly nonrevertible single nucleotide polymorphism (SNP) null mutations in\n            <jats:italic>cpsE<\/jats:italic>\n            , encoding the initiating glycosyltransferase. From a small collection of acapsular conjunctival isolates, we identified one strain with a complete capsular operon but containing a SNP in\n            <jats:italic>cpsE<\/jats:italic>\n            that we show is responsible for the acapsular phenotype. We propose that acapsular conjunctival isolates may arise initially from such nonreverting SNP null mutations in\n            <jats:italic>cpsE<\/jats:italic>\n            , which can be followed later by deletion of portions or all of the\n            <jats:italic>cps<\/jats:italic>\n            operon.\n          <\/jats:p>","DOI":"10.1128\/jb.02602-14","type":"journal-article","created":{"date-parts":[[2015,3,17]],"date-time":"2015-03-17T02:13:00Z","timestamp":1426558380000},"page":"1781-1791","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Mutations in Pneumococcal\n            <i>cpsE<\/i>\n            Generated via\n            <i>In Vitro<\/i>\n            Serial Passaging Reveal a Potential Mechanism of Reduced Encapsulation Utilized by a Conjunctival Isolate"],"prefix":"10.1128","volume":"197","author":[{"given":"Mara G.","family":"Shainheit","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"},{"name":"Department of Biological Sciences, Towson University, Towson, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Valentino","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Gilmore","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Camilli","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1871"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-2508(00)00175-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505113321907"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-009-0557-x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01475-06"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00857.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00881-09"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00862-12"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01056-09"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2005.11.001"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2009.01979.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.2436\/20.1501.01.84"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00425-08"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20430"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.7.2325-2335.2006"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12196"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0891-5520(20)30482-7","article-title":"Infectious conjunctivitis","volume":"6","author":"Syed NA","year":"1992","unstructured":"Syed NA, Hyndiuk RA. 1992. 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