{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:32:55Z","timestamp":1791142375005,"version":"4.1.0"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2009,6,1]],"date-time":"2009-06-01T00:00:00Z","timestamp":1243814400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    , the etiological agent of anthrax, is a gram-positive spore-forming bacterium. It produces edema toxin (EdTx), a powerful adenylate cyclase that increases cyclic AMP (cAMP) levels in host cells. Because other cAMP-increasing agents inhibit key macrophage (M\u03a6) functions, such as phagocytosis, it was hypothesized that EdTx would exhibit similar suppressive activities. Our previous GeneChip data showed that EdTx downregulated M\u03a6 genes involved in actin cytoskeleton remodeling, including protein kinase A (PKA). To further examine the role of EdTx during anthrax pathogenesis, we explored the hypothesis that EdTx treatment leads to deregulation of the cAMP-dependent PKA system, resulting in impaired cytoskeletal functions essential for M\u03a6 activity. Our data revealed that EdTx significantly suppressed human M\u03a6 phagocytosis of Ames spores. Cytoskeletal changes, such as decreased cell spreading and lowered F-actin content, were also observed for toxin-treated M\u03a6s. Further, EdTx altered the protein levels and activity of PKA and exchange protein activated by cAMP (Epac), a recently identified cAMP-binding molecule. By using PKA- and Epac-selective cAMP analogs, we confirmed the involvement of both pathways in the inhibition of M\u03a6 functions elicited by EdTx-generated cAMP. These results suggested that EdTx weakened the host immune response by increasing cAMP levels, which then signaled via PKA and Epac to cripple M\u03a6 phagocytosis and interfered with cytoskeletal remodeling.\n                  <\/jats:p>","DOI":"10.1128\/iai.00905-08","type":"journal-article","created":{"date-parts":[[2009,3,23]],"date-time":"2009-03-23T20:55:34Z","timestamp":1237841734000},"page":"2530-2543","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["<i>Bacillus anthracis<\/i>\n                    Edema Toxin Suppresses Human Macrophage Phagocytosis and Cytoskeletal Remodeling via the Protein Kinase A and Exchange Protein Activated by Cyclic AMP Pathways"],"prefix":"10.1128","volume":"77","author":[{"given":"Linsey A.","family":"Yeager","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok K.","family":"Chopra","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"},{"name":"Center for Biodefense and Emerging Infectious Diseases and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny W.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"},{"name":"Center for Biodefense and Emerging Infectious Diseases and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(00)01722-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.12.004"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408410490468795"},{"key":"e_1_3_2_5_2","first-page":"116","volume":"7","year":"1994","unstructured":"Akagawa, K. 1994. 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