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However, it has not been examined phenotypically in\n                      <jats:italic toggle=\"yes\">S. flexneri<\/jats:italic>\n                      6. Despite the impact of G4C, no systematic analysis of its expression or the presence of the genomic determinants has been performed across a large collection of\n                      <jats:italic toggle=\"yes\">S. sonnei<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">S. flexneri<\/jats:italic>\n                      serotypes 2a and 6 or any of the other &gt;46\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      strains and serotypes that cause disease. Our examination of the genomes of 1,219 geographically diverse\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      isolates revealed the presence of intact\n                      <jats:italic toggle=\"yes\">gfc<\/jats:italic>\n                      operons not only in the majority (\u226598%) of\n                      <jats:italic toggle=\"yes\">S. sonnei<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">S. flexneri<\/jats:italic>\n                      6 strains but also, surprisingly, in the majority (\u226597%) of\n                      <jats:italic toggle=\"yes\">Shigella boydii<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Shigella dysenteriae<\/jats:italic>\n                      strains. Approximately 95% of non-serotype 6\n                      <jats:italic toggle=\"yes\">S. flexneri<\/jats:italic>\n                      isolates contained a range of diverse\n                      <jats:italic toggle=\"yes\">gfc<\/jats:italic>\n                      mutations preventing G4C expression; the remaining 5% contained an intact\n                      <jats:italic toggle=\"yes\">gfc<\/jats:italic>\n                      operon yet had single-nucleotide polymorphisms within the promoter that resulted in lack of expression. These findings establish that no\n                      <jats:italic toggle=\"yes\">S. flexneri<\/jats:italic>\n                      serotypes other than 6 express a G4C. Capsule expression was directly linked to reduced epithelial cell invasion for all strains examined, confirming differences in pathogenic processes between capsule-positive and capsule-negative\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      strains. This work identifies a more widespread expression of capsule among\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      strains than previously appreciated and identifies critical genetic requirements.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      is the leading cause of moderate-to-severe diarrhea in 1- to 5-year-old children in low-resource settings, yet there is no licensed vaccine. Despite the impact of the group 4 capsule (G4C) on\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      epithelial cell invasion, its expression has not been determined for the majority of\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      species and serotypes that cause disease. This study investigated the presence of intact genes necessary for G4C expression in 1,219 geographically diverse\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      isolates and examined phenotypes associated with G4C expression. We report that G4C is much more widespread than previously appreciated; it is expressed in the vast majority of\n                      <jats:italic toggle=\"yes\">Shigella sonnei<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Shigella flexneri<\/jats:italic>\n                      6 clinical isolates, as well as\n                      <jats:italic toggle=\"yes\">Shigella boydii<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Shigella dysenteriae<\/jats:italic>\n                      strains. No\n                      <jats:italic toggle=\"yes\">S. flexneri<\/jats:italic>\n                      serotypes outside of serotype 6 expressed a G4C. This study provides evidence that G4C expression in\n                      <jats:italic toggle=\"yes\">Shigella<\/jats:italic>\n                      is much more widespread than previously recognized and emphasizes the importance of capsule expression in host\u2013pathogen interactions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00354-26","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:05:33Z","timestamp":1786539933000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Expanded prevalence of group 4 capsule expression and its genetic requirements in a broad array of\n                    <i>Shigella<\/i>\n                    strains"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1279-5763","authenticated-orcid":true,"given":"Brock 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