{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:47:40Z","timestamp":1791899260454,"version":"4.3.4"},"reference-count":70,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI154047"],"award-info":[{"award-number":["AI154047"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019346","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA012197"],"award-info":[{"award-number":["P30CA012197"]}],"id":[{"id":"10.13039\/100019346","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Streptococcus pneumoniae<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Spn<\/jats:italic>\n                      ) asymptomatically colonizes the upper respiratory tract (URT), a niche from which it can transmit to another host or cause invasive disease in the same host. The\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      transcriptional adaptations that\n                      <jats:italic toggle=\"yes\">Spn<\/jats:italic>\n                      undergoes during nasopharyngeal colonization, particularly during influenza A virus (IAV) co-infection, are poorly understood. Here, we leveraged an established infant mouse model of colonization, shedding, and transmission to perform genome-wide transcriptomic profiling of\n                      <jats:italic toggle=\"yes\">Spn<\/jats:italic>\n                      during mono- and during IAV co-infection. Compared with broth-grown controls, pneumococci isolated from the URT exhibited distinct transcriptional programs, with over 200 genes differentially expressed across time points. Genes involved in carbohydrate uptake and metabolism, glycan degradation, amino sugar and nucleotide sugar metabolism, and amino acid biosynthesis were consistently enriched during colonization, highlighting metabolic adaptation to the nasopharyngeal niche. In contrast, IAV co-infection induced a markedly distinct transcriptional signature, including upregulation of branched-chain amino acid biosynthesis, bacteriocin production, and phosphate acquisition systems. Notably, the pilus islet-1 locus was upregulated during\n                      <jats:italic toggle=\"yes\">Spn<\/jats:italic>\n                      -IAV co-infection. Functional studies demonstrated that while the pilus was dispensable for colonization under mono- and co-infection conditions, it promoted high-shedding events and enhanced inflammatory responses during IAV co-infection. However, reduced inflammation and reduced high-shedding events from pups inoculated with a pilus-deficient mutant did not alter transmission frequency in the infant mouse model. Collectively, our findings define the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      transcriptional landscape of\n                      <jats:italic toggle=\"yes\">Spn<\/jats:italic>\n                      during URT colonization and reveal distinct bacterial adaptations during viral co-infection, providing insight into mechanisms that influence pneumococcal persistence, inflammation, and transmission.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00323-26","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:30:28Z","timestamp":1788366628000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Influenza A virus co-infection alters\n                    <i>Streptococcus pneumoniae<\/i>\n                    gene expression during upper respiratory tract colonization"],"prefix":"10.1128","volume":"94","author":[{"given":"Noah A.","family":"Nutter","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine","place":["Winston-Salem, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Costa-Terryll","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine","place":["Winston-Salem, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance M.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Wake Forest School of Medicine","place":["Winston-Salem, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Leung","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0512csj88","id-type":"ROR","asserted-by":"publisher"}],"name":"Atrium Health Wake Forest Baptist Comprehensive Cancer Center","place":["Winston-Salem, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengbo","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0512csj88","id-type":"ROR","asserted-by":"publisher"}],"name":"Atrium Health Wake Forest Baptist Comprehensive Cancer Center","place":["Winston-Salem, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Maidul","family":"Islam","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Emory University School of Medicine","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Fecko","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0190ak572","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, New York University School of Medicine","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3737-0422","authenticated-orcid":true,"given":"M. Ammar","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine","place":["Winston-Salem, USA"]},{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Emory University School of Medicine","place":["Atlanta, 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