{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:32:05Z","timestamp":1787016725812,"version":"build-2736575974"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["U19AI110820"],"award-info":[{"award-number":["U19AI110820"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["U19 AI142725"],"award-info":[{"award-number":["U19 AI142725"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,1,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Shigella flexneri<\/jats:italic>\n serotype 6 (\n Sf<\/jats:italic>\n 6) is one of the most common serotypes recovered from surveillance studies of moderate to severe diarrhea. Despite the clinical significance of\n Sf<\/jats:italic>\n 6, this serotype is understudied. In this work, we have performed both serotype-specific genomic and phenotypic comparisons of\n Sf<\/jats:italic>\n 6 isolates to one another and non-\n S<\/jats:italic>\n .\n flexneri<\/jats:italic>\n serotypes. Comparative genomic analyses identified significant nucleotide homology between\n Sf<\/jats:italic>\n 6 strains (\n n<\/jats:italic>\n = 325), despite a broad range of collection timeframes and geographic locations. We identified\n Sf<\/jats:italic>\n 6 specific factors, including a potential novel\n Shigella<\/jats:italic>\n virulence factor (type II secretion system). Additionally, we identified established\n Shigella<\/jats:italic>\n virulence genes (\n ospG<\/jats:italic>\n ) and metabolic genes (\n rutABCDEFGR<\/jats:italic>\n ) that were absent in\n Sf<\/jats:italic>\n 6 strains while present in the majority of 728 non-\n Sf<\/jats:italic>\n 6 strains. Complete sequencing of 11 clinical\n Sf<\/jats:italic>\n 6 strains, demonstrated that the\n Sf<\/jats:italic>\n 6 virulence plasmid (pINV) is ~38 kb smaller than the average non-\n Sf<\/jats:italic>\n 6 pINV (~228 kb). Comparisons of\n S. flexneri<\/jats:italic>\n species level antibiotic susceptibility highlighted that clinical\n Sf<\/jats:italic>\n 6 isolates from Africa in the Global Enteric Multicenter Study (GEMS) and Vaccine Impact on Diarrhea in Africa (VIDA) study demonstrated geographic, serotype-specific susceptibility pattern. Phenotypic analyses of\n Sf<\/jats:italic>\n 6 identified reduced intracellular invasion and cytokine induction from HT-29 cells, as well as reduced Ipa protein effector secretion, compared with\n S. flexneri<\/jats:italic>\n serotype 2a strain 2457T. Together these data highlight conserved and unique serotype-specific genotypic and phenotypic features for\n Sf<\/jats:italic>\n 6. This level of conservation has not been noted for other\n S. flexneri<\/jats:italic>\n serotypes and is promising for vaccine and diagnostic assays to provide global\n Sf<\/jats:italic>\n 6-specific coverage.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n Shigellosis is an ongoing global public health crisis with >270 million annual episodes among all age groups; however, the greatest disease burden is among children in low- and middle-income countries (LMIC). The lack of a licensed\n Shigella<\/jats:italic>\n vaccine and the observed rise in antimicrobial-resistant\n Shigella<\/jats:italic>\n spp. highlights the urgency for effective preventative and interventional strategies. The inclusion of\n S. flexneri<\/jats:italic>\n serotype 6 (\n Sf<\/jats:italic>\n 6) is a necessary component of a multivalent vaccine strategies based on its clinical and epidemiological importance. Given the genomic diversity of\n Sf<\/jats:italic>\n 6 compared with other\n S. flexneri<\/jats:italic>\n serotypes and\n Sf<\/jats:italic>\n 6 unique O-antigen core structure, serotype-specific characterization of\n Sf<\/jats:italic>\n 6 is a critical step to inform\n Shigella<\/jats:italic>\n -directed vaccine and alternative therapeutic designs. Herein, we identified conserved genomic content among a large collection of temporally and geographically diverse\n Sf<\/jats:italic>\n 6 clinical isolates and characterized genotypic and phenotypic properties that separate\n Sf<\/jats:italic>\n 6 from non-\n Sf<\/jats:italic>\n 6\n S. flexneri<\/jats:italic>\n serotypes.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/mbio.02210-24","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T09:01:24Z","timestamp":1733821284000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of\n Shigella flexneri<\/i>\n serotype 6 strains from geographically diverse low- and middle-income countries"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7482-9060","authenticated-orcid":true,"given":"Caitlin E.","family":"Gabor","sequence":"first","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Cambridge","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M.","family":"Lemme-Dumit","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Department of Pediatrics, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy H.","family":"Hazen","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate S.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Cambridge","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Kotloff","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Department of Pediatrics, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Department of Medicine, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene N.","family":"Kasumba","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Department of Medicine, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0651-5748","authenticated-orcid":true,"given":"Sharon M.","family":"Tennant","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Department of Medicine, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Badji","sequence":"additional","affiliation":[{"name":"Medical Research Council Unit, The Gambia at the London School of Hygiene & Tropical Medicine","place":["Banjul, The Gambia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Jahangir","family":"Hossain","sequence":"additional","affiliation":[{"name":"Medical Research Council Unit, The Gambia at the London School of Hygiene & Tropical Medicine","place":["Banjul, The Gambia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Omore","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute, Center for Global Health Research (KEMRI-CGHR)","place":["Kisumu, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Ochieng","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute, Center for Global Health Research (KEMRI-CGHR)","place":["Kisumu, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex O.","family":"Awuor","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute, Center for Global Health Research (KEMRI-CGHR)","place":["Kisumu, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy","family":"Ogwel","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute, Center for Global Health Research (KEMRI-CGHR)","place":["Kisumu, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Juma","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute, Center for Global Health Research (KEMRI-CGHR)","place":["Kisumu, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5326-0047","authenticated-orcid":false,"given":"Eileen M.","family":"Barry","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7337-7154","authenticated-orcid":true,"given":"David A.","family":"Rasko","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine","place":["Baltimore, USA"]},{"name":"Center for Pathogen Research, University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32203-7"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31529-X"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu468"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30401-3"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07335"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-021-01054-z"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33296-8"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60844-2"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac969"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1662"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1099\/00207713-22-3-149"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.2307\/4589876"},{"key":"e_1_3_4_14_2","first-page":"31","article-title":"A series of cases of tropical infantile dysentery with a hitherto undescribed bacillus as the causitative agent","volume":"3","author":"Bowman FB","year":"1908","unstructured":"Bowman FB. 1908. 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