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The mechanisms allowing<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>to overcome toxic reactive oxygen molecules produced by the innate immune system are an integral part of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>'s ability to survive during infection. To probe the contribution of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>catalases in oxidative stress defense, we created and analyzed the virulence defects of mutants lacking CatB and CatP, which are responsible for extracellular and intracellular catalase activities, respectively. Both CatB and CatP protected<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>from peroxide challenge<jats:italic>in vitro<\/jats:italic>and from antimicrobial reactive oxygen produced by human neutrophils and activated macrophages. Optimal protection required both catalases, as the survival of a double mutant lacking both CatB and CatP was lower than that of single-catalase-deficient cells. Although CatB contributed to reactive oxygen species defenses<jats:italic>in vitro<\/jats:italic>, CatB was dispensable for lung infection and extrapulmonary dissemination<jats:italic>in vivo<\/jats:italic>. Loss of CatB from a strain also lacking superoxide dismutase (Sod3) did not further reduce the survival of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>yeasts. Nevertheless, some catalase function was required for pathogenesis since simultaneous loss of both CatB and CatP attenuated<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>virulence<jats:italic>in vivo<\/jats:italic>. These results demonstrate that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>'s dual catalases comprise a system that enables<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>to efficiently overcome the reactive oxygen produced by the innate immune system.<\/jats:p>","DOI":"10.1128\/iai.00173-13","type":"journal-article","created":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T01:07:53Z","timestamp":1366074473000},"page":"2334-2346","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":67,"title":["Redundant Catalases Detoxify Phagocyte Reactive Oxygen and Facilitate Histoplasma capsulatum Pathogenesis"],"prefix":"10.1128","volume":"81","author":[{"given":"Eric D.","family":"Holbrook","sequence":"first","affiliation":[{"name":"Department of Microbiology and Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Smolnycki","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian H.","family":"Youseff","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad A.","family":"Rappleye","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"6732","DOI":"10.4049\/jimmunol.163.12.6732","article-title":"NADPH oxidase activation and assembly during phagocytosis","volume":"163","author":"DeLeo FR","year":"1999","unstructured":"DeLeoFRAllenLAApicellaMNauseefWM. 1999. 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