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The pathogenic process involves bacterial invasion and lysis of the phagocytic vacuole, followed by replication and movement within the cell cytoplasm and, ultimately, spread directly into adjacent cells. This study demonstrates that\n            <jats:italic>S. flexneri<\/jats:italic>\n            cytochrome\n            <jats:italic>bd<\/jats:italic>\n            expression is necessary for normal intracellular survival and virulence. Cytochrome\n            <jats:italic>bd<\/jats:italic>\n            is one of two terminal oxidases in the bacterial respiratory chain that reduce molecular oxygen to water, utilizing intermediates shuttled through the electron transport chain.\n            <jats:italic>S. flexneri<\/jats:italic>\n            mutants that contain a disruption in the\n            <jats:italic>cydC<\/jats:italic>\n            locus, which leads to defective cytochrome\n            <jats:italic>bd<\/jats:italic>\n            expression, or in the riboflavin (\n            <jats:italic>ribE<\/jats:italic>\n            ) or ubiquinol-8 (\n            <jats:italic>ubiH<\/jats:italic>\n            ) biosynthetic pathway, which leads to elevated cytochrome\n            <jats:italic>bd<\/jats:italic>\n            expression, were evaluated in intracellular survival and virulence assays. The\n            <jats:italic>cydC<\/jats:italic>\n            mutant formed significantly smaller plaques, had significantly decreased intracellular survival, and had a 100-fold increase in lethal dose for mice compared with the wild type. The\n            <jats:italic>ribE<\/jats:italic>\n            and\n            <jats:italic>ubiH<\/jats:italic>\n            mutants each formed significantly larger plaques and had a 10-fold decrease in lethal dose for mice compared with the wild type. The data indicate that expression of cytochrome\n            <jats:italic>bd<\/jats:italic>\n            is required for\n            <jats:italic>S. flexneri<\/jats:italic>\n            intracellular survival and virulence.\n          <\/jats:p>","DOI":"10.1128\/jb.181.4.1229-1237.1999","type":"journal-article","created":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T16:45:21Z","timestamp":1577810721000},"page":"1229-1237","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":89,"title":["Impact of either Elevated or Decreased Levels of Cytochrome\n            <i>bd<\/i>\n            Expression on\n            <i>Shigella flexneri<\/i>\n            Virulence"],"prefix":"10.1128","volume":"181","author":[{"given":"Sing Sing","family":"Way","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Sallustio","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Magliozzo","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Physiology and Biophysics,2 Albert Einstein College of Medicine, Bronx, New York 10461-1602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia B.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.6.1997-2005.1991"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"10079","DOI":"10.1073\/pnas.89.21.10079","article-title":"Salmonella typhimurium activates virulence gene transcription within acidified macrophage phagosomes","volume":"89","author":"Aranda C. 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