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Death of an infected host cell can either facilitate release and dissemination of intracellular pathogens or promote pathogen clearance. <jats:styled-content style=\"fixed-case\"><jats:italic>H<\/jats:italic><\/jats:styled-content><jats:italic>istoplasma capsulatum<\/jats:italic> is an intracellular fungal pathogen that replicates robustly within macrophages and triggers macrophage lysis by unknown means. To identify <jats:styled-content style=\"fixed-case\"><jats:italic>H<\/jats:italic><\/jats:styled-content>. <jats:italic>capsulatum<\/jats:italic> effectors of macrophage lysis, we performed a genetic screen and discovered three mutants that grew to wild\u2010type levels within macrophages but failed to elicit host\u2010cell death. Each mutant was defective in production of the previously identified secreted protein <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>bp1 (calcium\u2010binding protein 1), whose role in intracellular growth had not been fully investigated. We found that <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>bp1 was dispensable for high levels of intracellular growth but required to elicit a unique transcriptional signature in macrophages, including genes whose induction was previously associated with endoplasmic reticulum stress and host\u2010cell death. Additionally, <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>bp1 was required for activation of cell\u2010death caspases\u20103\/7, and macrophage death during <jats:styled-content style=\"fixed-case\"><jats:italic>H<\/jats:italic><\/jats:styled-content>. <jats:italic>capsulatum<\/jats:italic> infection was dependent on the pro\u2010apoptotic proteins Bax and Bak. Taken together, these findings strongly suggest that the ability of <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>bp1 to actively program host\u2010cell death is an essential step in <jats:styled-content style=\"fixed-case\"><jats:italic>H<\/jats:italic><\/jats:styled-content>. <jats:italic>capsulatum<\/jats:italic> pathogenesis.<\/jats:p>","DOI":"10.1111\/mmi.13168","type":"journal-article","created":{"date-parts":[[2015,8,19]],"date-time":"2015-08-19T15:39:19Z","timestamp":1439998759000},"page":"910-929","source":"Crossref","is-referenced-by-count":46,"title":["Macrophage cell death and transcriptional response are actively triggered by the fungal virulence factor <scp>C<\/scp>bp1 during <scp><i>H<\/i><\/scp>. <i>capsulatum<\/i> infection"],"prefix":"10.1111","volume":"98","author":[{"given":"Dervla T.","family":"Isaac","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of California San Francisco  San Francisco CA 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