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However, nonopsonic antibodies may also be important for protection against pneumococcal disease. For example, 1E2, a mouse IgG1 monoclonal antibody (MAb) to the serotype 3 (ST3) PPS (PPS3), reduced ST3 NP colonization in mice and altered ST3 gene expression<jats:italic>in vitro<\/jats:italic>. Here, we determined whether 1E2 affects ST3 gene expression<jats:italic>in vivo<\/jats:italic>during colonization of mice by performing RNA sequencing on NP lavage fluid from ST3-infected mice treated with 1E2, a control MAb, or phosphate-buffered saline. Compared to the results for the controls, 1E2 significantly altered the expression of over 50 genes. It increased the expression of the<jats:italic>piuBCDA<\/jats:italic>operon, which encodes an iron uptake system, and decreased the expression of<jats:italic>dpr<\/jats:italic>, which encodes a protein critical for resistance to oxidative stress. 1E2-mediated effects on ST3<jats:italic>in vivo<\/jats:italic>required divalent binding, as Fab fragments did not reduce NP colonization or alter ST3 gene expression.<jats:italic>In vitro<\/jats:italic>, 1E2 induced dose-dependent ST3 growth arrest and altered<jats:italic>piuB<\/jats:italic>and<jats:italic>dpr<\/jats:italic>expression, whereas an opsonic PPS3 MAb, 5F6, did not. 1E2-treated bacteria were more sensitive to hydrogen peroxide and the iron-requiring antibiotic streptonigrin, suggesting that 1E2 may increase iron import and enhance sensitivity to oxidative stress. Finally, 1E2 also induced rapid capsule shedding<jats:italic>in vitro<\/jats:italic>, suggesting that this may initiate 1E2-induced changes in sensitivity to oxidative stress and gene expression. Our data reveal a novel mechanism of direct, antibody-mediated antibacterial activity that could inform new directions in antipneumococcal therapy and vaccine development.<\/jats:p>","DOI":"10.1128\/iai.00300-18","type":"journal-article","created":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T09:33:50Z","timestamp":1525685630000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["A Capsular Polysaccharide-Specific Antibody Alters Streptococcus pneumoniae Gene Expression during Nasopharyngeal Colonization of Mice"],"prefix":"10.1128","volume":"86","author":[{"given":"Christopher R.","family":"Doyle","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine &amp; Montefiore Medical Center, Bronx, New York, 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