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However, it is unknown if bacterial targeting to these sites is mediated by multifunctional or distinct chlamydial factors. We previously showed that disruption of individual large clostridial toxin homologs encoded within the\n            <jats:named-content content-type=\"genus-species\">Chlamydia muridarum<\/jats:named-content>\n            plasticity zone were not critical for murine genital tract infection. Here, we assessed whether cytotoxin genes contribute to\n            <jats:named-content content-type=\"genus-species\">C. muridarum<\/jats:named-content>\n            GI tropism. Infectivity and shedding of wild-type (WT)\n            <jats:named-content content-type=\"genus-species\">C. muridarum<\/jats:named-content>\n            and three mutants containing nonsense mutations in different cytotoxin genes,\n            <jats:italic>tc0437<\/jats:italic>\n            ,\n            <jats:italic>tc0438<\/jats:italic>\n            , and\n            <jats:italic>tc0439<\/jats:italic>\n            , were compared in mouse genital and GI infection models. One mutant, which had a nonsense mutation in\n            <jats:italic>tc0439<\/jats:italic>\n            , was highly attenuated for GI infection and had a GI 50% infectious dose (ID\n            <jats:sub>50<\/jats:sub>\n            ) that was 1,000 times greater than that of the WT. GI inoculation with this mutant failed to elicit anti-chlamydial antibodies or to protect against subsequent genital tract infection. Genome sequencing of the\n            <jats:italic>tc0439<\/jats:italic>\n            mutant revealed additional chromosomal mutations, and phenotyping of additional mutants suggested that the GI attenuation might be linked to a nonsense mutation in\n            <jats:italic>tc0600<\/jats:italic>\n            . The molecular mechanism underlying this dramatic difference in tissue-tropic virulence is not fully understood. However, isolation of these mutants demonstrates that distinct chlamydial chromosomal factors mediate chlamydial tissue tropism and provides a basis for vaccine initiatives to isolate chlamydia strains that are attenuated for genital infection but retain the ability to colonize the GI tract and elicit protective immune responses.\n          <\/jats:p>","DOI":"10.1128\/iai.00141-18","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T09:52:40Z","timestamp":1523958760000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Chlamydia muridarum Genital and Gastrointestinal Infection Tropism Is Mediated by Distinct Chromosomal Factors"],"prefix":"10.1128","volume":"86","author":[{"given":"Sandra G.","family":"Morrison","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Giebel","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn C.","family":"Toh","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Horace J.","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9747-9884","authenticated-orcid":false,"given":"Richard P.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Sexually transmitted disease surveillance 2016","author":"Centers for Disease Control and Prevention","year":"2017","unstructured":"Centers for Disease Control and Prevention. 2017. 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