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One key\n            <jats:italic>Spn<\/jats:italic>\n            virulence factor is pneumococcal surface protein A (PspA), which promotes survival by blocking the antimicrobial peptide lactoferricin. PspA has also been shown to mediate attachment to dying epithelial cells in the lower airway due to its binding of cell surface-bound mammalian (m)GAPDH. Importantly, the role of PspA during colonization is not well understood. Wild-type\n            <jats:italic>Spn<\/jats:italic>\n            was present in nasal lavage elutes collected from asymptomatically colonized mice at levels ~10-fold higher than its isogenic PspA-deficient mutant (\u2206\n            <jats:italic>pspA<\/jats:italic>\n            ). Wild-type\n            <jats:italic>Spn<\/jats:italic>\n            also formed aggregates in mucosal secretions composed of sloughed epithelial cells and hundreds of pneumococci, whereas \u2206\n            <jats:italic>pspA<\/jats:italic>\n            did not.\n            <jats:italic>Spn<\/jats:italic>\n            within the center of these aggregates better survived prolonged desiccation on fomites than individual pneumococci and were capable of infecting na\u00efve mice, indicating PspA-mediated aggregation conferred a survival\/transmission advantage. Incubation of\n            <jats:italic>Spn<\/jats:italic>\n            in saline containing mGAPDH also enhanced tolerance to desiccation, but only for wild-type\n            <jats:italic>Spn<\/jats:italic>\n            . mGAPDH was sufficient to cause low-level aggregation of wild-type\n            <jats:italic>Spn<\/jats:italic>\n            but not \u2206\n            <jats:italic>pspA<\/jats:italic>\n            . In strain WU2, the subdomain of PspA responsible for binding GAPDH (aa230\u2013281) is ensconced within the lactoferrin (LF)-binding domain (aa167-288). We observed that LF inhibited GAPDH-mediated aggregation and desiccation tolerance. Using surface plasmon resonance, we determined that\n            <jats:italic>Spn<\/jats:italic>\n            forms multimeric complexes of PspA-GAPDH-LF on its surface and that LF dislodges GAPDH. Our findings have important implications regarding pneumococcal colonization\/transmission processes and ongoing PspA-focused immunization efforts for this deadly pathogen.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Spn<\/jats:italic>\n              is a dangerous human pathogen capable of causing pneumonia and invasive disease. The virulence factor PspA has been studied for nearly four decades with well-established roles in pneumococcal evasion of C-reactive protein and neutralization of lactoferricin. Herein, we show that mammalian (m)GAPDH in mucosal secretions promotes aggregation of pneumococci in a PspA-dependent fashion, whereas lactoferrin counters this effect. PspA-mediated GAPDH-dependent bacterial aggregation protected\n              <jats:italic>Spn<\/jats:italic>\n              in nasal lavage elutes and grown\n              <jats:italic>in vitro<\/jats:italic>\n              from desiccation on fomites. Furthermore, surviving pneumococci within these aggregates retained their ability to colonize na\u00efve hosts after desiccation. We report that\n              <jats:italic>Spn<\/jats:italic>\n              binds to and forms protein complexes on its surface composed of PspA, mGAPDH, and lactoferrin. Changes in the levels of these proteins therefore most likely have critical implications on\n              <jats:italic>Spn<\/jats:italic>\n              colonization, survival on fomites, and transmission.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.02634-23","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T14:05:43Z","timestamp":1700489143000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["PspA-mediated aggregation protects\n            <i>Streptococcus pneumoniae<\/i>\n            against desiccation on fomites"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7094-5080","authenticated-orcid":false,"given":"Jessica R.","family":"Lane","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muralidhar","family":"Tata","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahena","family":"Yasmin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0629-7461","authenticated-orcid":false,"given":"Hansol","family":"Im","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Briles","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8542-4069","authenticated-orcid":false,"given":"Carlos J.","family":"Orihuela","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02185-7"},{"key":"e_1_3_5_3_2","first-page":"94","article-title":"Bacterial carriage and respiratory tract infections in subjects > or = 60 years during an influenza season: implications for the epidemiology of community acquired pneumonia and influenza vaccine effectiveness","volume":"53","author":"Ansaldi F","year":"2012","unstructured":"Ansaldi F, De Florentiis D, Parodi V, Rappazzo E, Coppelli M, Martini M, Alicino C, Durando P, Icardi G. 2012. 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