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The<jats:italic>cjrABC-senB<\/jats:italic>gene cluster of<jats:italic>E. coli<\/jats:italic>contributes to ExPEC virulence in the mouse model of UTIs. Consistently, the distribution of<jats:italic>cjrABC-senB<\/jats:italic>is epidemiologically associated with human UTIs caused by<jats:italic>E. coli<\/jats:italic>.<jats:italic>cjrABC-senB<\/jats:italic>, which has previously been proposed to encode an iron uptake system, may facilitate ExPEC survival in the iron availability-restricted urinary tract. Given that the bloodstream is also an iron limited environment to invading bacteria, the pathogenic role of<jats:italic>cjrABC-senB<\/jats:italic>in ExPEC bacteremia, however, remains to be investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The ability of ExPEC RS218 strains with and without<jats:italic>cjrABC-senB<\/jats:italic>to survive in the mouse bloodstream and human serum was evaluated. Subsequently, the role of this gene cluster in the ExPEC interaction with the complement system was evaluated. Finally, the distribution of<jats:italic>cjrABC-senB<\/jats:italic>in human clinical<jats:italic>E. coli<\/jats:italic>isolates was determined by PCR. The frequency of<jats:italic>cjrABC-senB<\/jats:italic>in bacteremia isolates that were not associated with UTIs (non-UTI bacteremia isolates) was compared with that in UTI-associated isolates and fecal isolates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of<jats:italic>cjrABC-senB<\/jats:italic>attenuated the survival of RS218 in the mouse bloodstream and human serum. The<jats:italic>cjrABC-senB<\/jats:italic>-harboring strains triggered enhanced classical- and alternative-complement pathway activation and became more vulnerable to complement-mediated killing in serum.<jats:italic>cjrA<\/jats:italic>was identified as the major gene responsible for the attenuated serum survival. Expressing<jats:italic>cjrABC-senB<\/jats:italic>and<jats:italic>cjrA<\/jats:italic>increased bacterial susceptibility to detergent and induced periplasmic protein leakage, suggesting that the expression of these genes compromises the integrity of the outer membrane of ExPEC. In addition, the frequency of<jats:italic>cjrABC-senB<\/jats:italic>in non-UTI bacteremia isolates was significantly lower than that in UTI-associated isolates, while the frequencies in non-UTI bacteremia isolates and fecal isolates showed no significant difference. Consistently, this epidemiological investigation suggests that<jats:italic>cjrABC-senB<\/jats:italic>does not contribute to<jats:italic>E. coli<\/jats:italic>bacteremia in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The contribution of<jats:italic>cjrABC-senB<\/jats:italic>to the pathogenesis of ExPEC is niche dependent and contradictory because the genes facilitate ExPEC UTIs but hinder bacteremia. The contradictory niche-dependent characteristic may benefit the development of novel strategies against<jats:italic>E. coli<\/jats:italic>-caused infections.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12929-020-00677-4","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T21:02:40Z","timestamp":1596747760000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["cjrABC-senB hinders survival of extraintestinal pathogenic E. coli in the bloodstream through triggering complement-mediated killing"],"prefix":"10.1186","volume":"27","author":[{"given":"Wen-Chun","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Jyun","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan-Fu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chishih","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Chuen","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4615-094X","authenticated-orcid":false,"given":"Ching-Hao","family":"Teng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"issue":"11","key":"677_CR1","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1089\/fpd.2013.1533","volume":"10","author":"M Mellata","year":"2013","unstructured":"Mellata M. 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All of the animal experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of National Cheng Kung University, Tainan City, Taiwan (Approval number. 99228). The procedures for collecting blood were approved by the Institutional Reviewer Board of National Cheng Kung University Hospital, Tainan City, Taiwan (IRB No. B-ER-101-361).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors do not have any commercial or other association that might pose a conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"86"}}