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Previous studies have indicated that the ability of<jats:italic>Y. pestis<\/jats:italic>to survive inside macrophages may be critical during the early stages of plague pathogenesis. To gain insights into the biology of intracellular<jats:italic>Y. pestis<\/jats:italic>and its environment following phagocytosis, we determined the genome-wide transcriptional profile of<jats:italic>Y. pestis<\/jats:italic>KIM5 replicating inside J774.1 macrophage-like cells using DNA microarrays. At 1.5, 4, and 8 h postinfection, a total of 801, 464, and 416<jats:italic>Y. pestis<\/jats:italic>genes were differentially regulated, respectively, compared to the level of gene expression of control bacteria grown in tissue culture medium. A number of stress-response genes, including those involved in detoxification of reactive oxygen species, as well as several metabolic genes involved in macromolecule synthesis, were significantly induced in intracellular<jats:italic>Y. pestis<\/jats:italic>, consistent with the presence of oxidative stress and nutrient starvation inside<jats:italic>Yersinia<\/jats:italic>-containing vacuoles. A putative stress-induced operon consisting of y2313, y2315, and y2316 (y2313-y2316), and a previously unidentified open reading frame,<jats:italic>orfX<\/jats:italic>, was studied further on the basis of its high level of intracellular expression. Mutant strains harboring either deletion, \u0394y2313-y2316 or \u0394<jats:italic>orfX<\/jats:italic>, exhibited diverse phenotypes, including reduced effector secretion by the type III secretion system, increased intracellular replication, and filamentous morphology of the bacteria growing inside macrophages. The results suggest a possible role for these genes in regulating cell envelope characteristics in the intracellular environment.<\/jats:p>","DOI":"10.1128\/iai.00062-10","type":"journal-article","created":{"date-parts":[[2010,6,22]],"date-time":"2010-06-22T02:00:21Z","timestamp":1277172021000},"page":"3700-3715","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Global Gene Expression Profiling of<i>Yersinia pestis<\/i>Replicating inside Macrophages Reveals the Roles of a Putative Stress-Induced Operon in Regulating Type III Secretion and Intracellular Cell Division"],"prefix":"10.1128","volume":"78","author":[{"given":"Hana S.","family":"Fukuto","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases"},{"name":"Department of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Svetlanov","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases"},{"name":"Department of Biochemistry and Cell, Biology Stony Brook University, Stony Brook, New York 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance E.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases"},{"name":"Department of Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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