{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:30:49Z","timestamp":1778635849706,"version":"3.51.4"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,10,9]],"date-time":"2013-10-09T00:00:00Z","timestamp":1381276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"},{"start":{"date-parts":[[2013,10,9]],"date-time":"2013-10-09T00:00:00Z","timestamp":1381276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The development of cardiovascular dysfunction and shock in patients with invasive <jats:italic>Bacillus anthracis<\/jats:italic> infection has a particularly poor prognosis. Growing evidence indicates that several bacterial components likely play important pathogenic roles in this injury. As with other pathogenic Gram-positive bacteria, the <jats:italic>B. anthracis<\/jats:italic> cell wall and its peptidoglycan constituent produce a robust inflammatory response with its attendant tissue injury, disseminated intravascular coagulation and shock. However, <jats:italic>B. anthracis<\/jats:italic> also produces lethal and edema toxins that both contribute to shock. Growing evidence suggests that lethal toxin, a metalloprotease, can interfere with endothelial barrier function as well as produce myocardial dysfunction. Edema toxin has potent adenyl cyclase activity and may alter endothelial function, as well as produce direct arterial and venous relaxation. Furthermore, both toxins can weaken host defense and promote infection. Finally, <jats:italic>B. anthracis<\/jats:italic> produces non-toxin metalloproteases which new studies show can contribute to tissue injury, coagulopathy and shock. In the future, an understanding of the individual pathogenic effects of these different components and their interactions will be important for improving the management of <jats:italic>B. anthracis<\/jats:italic> infection and shock.<\/jats:p>","DOI":"10.1186\/1741-7015-11-217","type":"journal-article","created":{"date-parts":[[2013,10,10]],"date-time":"2013-10-10T11:06:42Z","timestamp":1381403202000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["B. anthracisassociated cardiovascular dysfunction and shock: the potential contribution of both non-toxin and toxin components"],"prefix":"10.1186","volume":"11","author":[{"given":"Kenneth E","family":"Remy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xizhong","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter Q","family":"Eichacker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,10,9]]},"reference":[{"key":"1102_CR1","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/S0140-6736(10)60573-9","volume":"375","author":"MG Booth","year":"2010","unstructured":"Booth MG, Hood J, Brooks TJ, Hart A: Anthrax infection in drug users. Lancet. 2010, 375: 1345-1346.","journal-title":"Lancet"},{"key":"1102_CR2","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1007\/s00134-012-2541-0","volume":"38","author":"CW Hicks","year":"2012","unstructured":"Hicks CW, Sweeney DA, Cui X, Li Y, Eichacker PQ: An overview of anthrax infection including the recently identified form of disease in injection drug users. Intensive Care Med. 2012, 38: 1092-1104. 10.1007\/s00134-012-2541-0.","journal-title":"Intensive Care Med"},{"key":"1102_CR3","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1186\/cc12010","volume":"17","author":"M Booth","year":"2013","unstructured":"Booth M, Donaldson L, Xizhong C, Junfeng S, Eichacker P: Comparison of survivors and nonsurvivors in 27 confirmed injectional anthrax cases from the 2009 outbreak in scotland. Crit Care. 2013, 17: 668.","journal-title":"Crit Care"},{"key":"1102_CR4","volume-title":"An Outbreak of Anthrax among Drug Users in Scotland, December 2009 to December 2010","author":"National Anthrax Outbreak Control Team","year":"2011","unstructured":"National Anthrax Outbreak Control Team: An Outbreak of Anthrax among Drug Users in Scotland, December 2009 to December 2010. 2011, Glasgow: Health Protection Scotland"},{"key":"1102_CR5","doi-asserted-by":"publisher","first-page":"933","DOI":"10.3201\/eid0706.010604","volume":"7","author":"JA Jernigan","year":"2001","unstructured":"Jernigan JA, Stephens DS, Ashford DA, Omenaca C, Topiel MS, Galbraith M, Tapper M, Fisk TL, Zaki S, Popovic T, Meyer RF, Quinn CP, Harper SA, Fridkin SK, Sejvar JJ, Shepard CW, McConnell M, Guarner J, Shieh WJ, Malecki JM, Gerberding JL, Hughes JM, Perkins BA: Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. Emerg Infect Dis. 2001, 7: 933-944. 10.3201\/eid0706.010604.","journal-title":"Emerg Infect Dis"},{"key":"1102_CR6","doi-asserted-by":"publisher","first-page":"L355","DOI":"10.1152\/ajplung.00069.2012","volume":"303","author":"EJ Seeley","year":"2012","unstructured":"Seeley EJ, Matthay MA, Wolters PJ: Inflection points in sepsis biology: from local defense to systemic organ injury. Am J Physiol Lung Cell Mol Physiol. 2012, 303: L355-363. 10.1152\/ajplung.00069.2012.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"1102_CR7","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1097\/CCM.0b013e31819267fb","volume":"37","author":"I Cinel","year":"2009","unstructured":"Cinel I, Opal SM: Molecular biology of inflammation and sepsis: a primer. Crit Care Med. 2009, 37: 291-304. 10.1097\/CCM.0b013e31819267fb.","journal-title":"Crit Care Med"},{"key":"1102_CR8","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1001\/jama.2011.909","volume":"306","author":"AF Suffredini","year":"2011","unstructured":"Suffredini AF, Munford RS: Novel therapies for septic shock over the past 4 decades. JAMA. 2011, 306: 194-199. 10.1001\/jama.2011.909.","journal-title":"JAMA"},{"key":"1102_CR9","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1189\/jlb.0912437","volume":"93","author":"M Aziz","year":"2013","unstructured":"Aziz M, Jacob A, Yang WL, Matsuda A, Wang P: Current trends in inflammatory and immunomodulatory mediators in sepsis. J Leukocyte Biol. 2013, 93: 329-342. 10.1189\/jlb.0912437.","journal-title":"J Leukocyte Biol"},{"key":"1102_CR10","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.1128\/IAI.72.5.3069-3072.2004","volume":"72","author":"AK Pickering","year":"2004","unstructured":"Pickering AK, Merkel TJ: Macrophages release tumor necrosis factor alpha and interleukin-12 in response to intracellular Bacillus anthracis spores. Infect Immun. 2004, 72: 3069-3072. 10.1128\/IAI.72.5.3069-3072.2004.","journal-title":"Infect Immun"},{"key":"1102_CR11","doi-asserted-by":"publisher","first-page":"433","DOI":"10.2353\/ajpath.2006.051330","volume":"169","author":"DJ Stearns-Kurosawa","year":"2006","unstructured":"Stearns-Kurosawa DJ, Lupu F, Taylor FB, Kinasewitz G, Kurosawa S: Sepsis and pathophysiology of anthrax in a nonhuman primate model. Am J Pathol. 2006, 169: 433-444. 10.2353\/ajpath.2006.051330.","journal-title":"Am J Pathol"},{"key":"1102_CR12","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.micinf.2011.08.016","volume":"14","author":"A Guichard","year":"2012","unstructured":"Guichard A, Nizet V, Bier E: New insights into the biological effects of anthrax toxins: linking cellular to organismal responses. Microbes Infect. 2012, 14: 97-118. 10.1016\/j.micinf.2011.08.016.","journal-title":"Microbes Infect"},{"key":"1102_CR13","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1111\/jcmm.12075","volume":"17","author":"KM Coggeshall","year":"2013","unstructured":"Coggeshall KM, Lupu F, Ballard J, Metcalf JP, James JA, Farris D, Kurosawa S: The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax. J Cell Mol Med. 2013, 17: 914-920. 10.1111\/jcmm.12075.","journal-title":"J Cell Mol Med"},{"key":"1102_CR14","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.3390\/toxins3091185","volume":"3","author":"CW Hicks","year":"2011","unstructured":"Hicks CW, Cui X, Sweeney DA, Li Y, Barochia A, Eichacker PQ: The potential contributions of lethal and edema toxins to the pathogenesis of anthrax associated shock. Toxins. 2011, 3: 1185-1202. 10.3390\/toxins3091185.","journal-title":"Toxins"},{"key":"1102_CR15","doi-asserted-by":"publisher","first-page":"2880","DOI":"10.1111\/j.1462-5822.2007.01003.x","volume":"9","author":"M Triantafilou","year":"2007","unstructured":"Triantafilou M, Uddin A, Maher S, Charalambous N, Hamm TS, Alsumaiti A, Triantafilou K: Anthrax toxin evades toll-like receptor recognition, whereas its cell wall components trigger activation via tlr2\/6 heterodimers. Cell Microbiol. 2007, 9: 2880-2892. 10.1111\/j.1462-5822.2007.01003.x.","journal-title":"Cell Microbiol"},{"key":"1102_CR16","doi-asserted-by":"publisher","first-page":"e3706","DOI":"10.1371\/journal.pone.0003706","volume":"3","author":"M Langer","year":"2008","unstructured":"Langer M, Malykhin A, Maeda K, Chakrabarty K, Williamson KS, Feasley CL, West CM, Metcalf JP, Coggeshall KM: Bacillus anthracis peptidoglycan stimulates an inflammatory response in monocytes through the p38 mitogen-activated protein kinase pathway. PLoS One. 2008, 3: e3706-10.1371\/journal.pone.0003706.","journal-title":"PLoS One"},{"key":"1102_CR17","doi-asserted-by":"publisher","first-page":"2418","DOI":"10.1128\/IAI.00170-10","volume":"78","author":"JK Iyer","year":"2010","unstructured":"Iyer JK, Khurana T, Langer M, West CM, Ballard JD, Metcalf JP, Merkel TJ, Coggeshall KM: Inflammatory cytokine response to Bacillus anthracis peptidoglycan requires phagocytosis and lysosomal trafficking. Infect Immun. 2010, 78: 2418-2428. 10.1128\/IAI.00170-10.","journal-title":"Infect Immun"},{"key":"1102_CR18","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1007\/s00134-009-1643-9","volume":"36","author":"X Cui","year":"2010","unstructured":"Cui X, Su J, Li Y, Shiloach J, Solomon S, Kaufman JB, Mani H, Fitz Y, Weng J, Altaweel L, Besch V, Eichacker PQ: Bacillus anthracis cell wall produces injurious inflammation but paradoxically decreases the lethality of anthrax lethal toxin in a rat model. Intensive Care Med. 2010, 36: 148-156. 10.1007\/s00134-009-1643-9.","journal-title":"Intensive Care Med"},{"key":"1102_CR19","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1093\/infdis\/jit247","volume":"208","author":"P Qiu","year":"2013","unstructured":"Qiu P, Li Y, Shiloach J, Cui X, Sun J, Trinh L, Kubler-Kielb J, Vinogradov E, Mani H, Al-Hamad M, Fitz Y, Eichacker PQ: B. anthracis cell wall peptidoglycan but not lethal or edema toxins produces changes consistent with disseminated intravascular coagulation in a rat model. J Infect Dis. 2013, 208: 978-989. 10.1093\/infdis\/jit247.","journal-title":"J Infect Dis"},{"key":"1102_CR20","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1182\/blood-2013-02-486613","volume":"122","author":"D Sun","year":"2013","unstructured":"Sun D, Popescu NI, Raisley B, Keshari RS, Dale GL, Lupu F, Coggeshall KM: Bacillus anthracis peptidoglycan activates human platelets through Fc?RII and complement. Blood. 2013, 122: 571-579. 10.1182\/blood-2013-02-486613.","journal-title":"Blood"},{"key":"1102_CR21","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1164\/rccm.201102-0209CI","volume":"184","author":"DA Sweeney","year":"2011","unstructured":"Sweeney DA, Hicks CW, Cui X, Li Y, Eichacker PQ: Anthrax infection. Am J Resp Crit Care. 2011, 184: 1333-1341. 10.1164\/rccm.201102-0209CI.","journal-title":"Am J Resp Crit Care"},{"key":"1102_CR22","doi-asserted-by":"publisher","first-page":"76","DOI":"10.3389\/fcimb.2012.00076","volume":"2","author":"DE Lowe","year":"2012","unstructured":"Lowe DE, Glomski IJ: Cellular and physiological effects of anthrax exotoxin and its relevance to disease. Front Cell Infect Microbiol. 2012, 2: 76.","journal-title":"Front Cell Infect Microbiol"},{"key":"1102_CR23","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.chom.2010.10.004","volume":"8","author":"S Liu","year":"2010","unstructured":"Liu S, Miller-Randolph S, Crown D, Moayeri M, Sastalla I, Okugawa S, Leppla SH: Anthrax toxin targeting of myeloid cells through the CMG2 receptor is essential for establishment of Bacillus anthracis infections in mice. Cell Host Microbe. 2010, 8: 455-462. 10.1016\/j.chom.2010.10.004.","journal-title":"Cell Host Microbe"},{"key":"1102_CR24","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1002\/pro.2231","volume":"22","author":"N Akkaladevi","year":"2013","unstructured":"Akkaladevi N, Hinton-Chollet L, Katayama H, Mitchell J, Szerszen L, Mukherjee S, Gogol EP, Pentelute BL, Collier RJ, Fisher MT: Assembly of anthrax toxin pore: lethal-factor complexes into lipid nanodiscs. Protein Sci. 2013, 22: 492-501. 10.1002\/pro.2231.","journal-title":"Protein Sci"},{"key":"1102_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/toxins5010001","volume":"5","author":"S Liu","year":"2013","unstructured":"Liu S, Zhang Y, Hoover B, Leppla SH: The receptors that mediate the direct lethality of anthrax toxin. Toxins. 2013, 5: 1-8.","journal-title":"Toxins"},{"key":"1102_CR26","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.mam.2009.07.003","volume":"30","author":"M Moayeri","year":"2009","unstructured":"Moayeri M, Leppla SH: Cellular and systemic effects of anthrax lethal toxin and edema toxin. Mol Aspects Med. 2009, 30: 439-455. 10.1016\/j.mam.2009.07.003.","journal-title":"Mol Aspects Med"},{"key":"1102_CR27","doi-asserted-by":"publisher","first-page":"e1003452","DOI":"10.1371\/journal.ppat.1003452","volume":"9","author":"J Chavarria-Smith","year":"2013","unstructured":"Chavarria-Smith J, Vance RE: Direct proteolytic cleavage of NLRP1B is necessary and sufficient for inflammasome activation by anthrax lethal factor. PLoS Pathog. 2013, 9: e1003452-10.1371\/journal.ppat.1003452.","journal-title":"PLoS Pathog"},{"key":"1102_CR28","doi-asserted-by":"publisher","first-page":"e1002638","DOI":"10.1371\/journal.ppat.1002638","volume":"8","author":"JL Levinsohn","year":"2012","unstructured":"Levinsohn JL, Newman ZL, Hellmich KA, Fattah R, Getz MA, Liu S, Sastalla I, Leppla SH, Moayeri M: Anthrax lethal factor cleavage of NLRP1 is required for activation of the inflammasome. PLoS Pathog. 2012, 8: e1002638-10.1371\/journal.ppat.1002638.","journal-title":"PLoS Pathog"},{"key":"1102_CR29","doi-asserted-by":"publisher","first-page":"2264","DOI":"10.1016\/j.bpj.2010.07.044","volume":"99","author":"E Laine","year":"2010","unstructured":"Laine E, Martinez L, Blondel A, Malliavin TE: Activation of the edema factor of Bacillus anthracis by calmodulin: evidence of an interplay between the EF-calmodulin interaction and calcium binding. Biophys J. 2010, 99: 2264-2272. 10.1016\/j.bpj.2010.07.044.","journal-title":"Biophys J"},{"key":"1102_CR30","doi-asserted-by":"publisher","first-page":"5494","DOI":"10.1021\/bi100684g","volume":"49","author":"M Gottle","year":"2010","unstructured":"Gottle M, Dove S, Kees F, Schlossmann J, Geduhn J, Konig B, Shen Y, Tang WJ, Kaever V, Seifert R: Cytidylyl and uridylyl cyclase activity of Bacillus anthracis edema factor and Bordetella pertussis CyaA. Biochemistry. 2010, 49: 5494-5503. 10.1021\/bi100684g.","journal-title":"Biochemistry"},{"key":"1102_CR31","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1086\/657408","volume":"202","author":"DA Sweeney","year":"2010","unstructured":"Sweeney DA, Cui X, Solomon SB, Vitberg DA, Migone TS, Scher D, Danner RL, Natanson C, Subramanian GM, Eichacker PQ: Anthrax lethal and edema toxins produce different patterns of cardiovascular and renal dysfunction and synergistically decrease survival in canines. J Infect Dis. 2010, 202: 1885-1896. 10.1086\/657408.","journal-title":"J Infect Dis"},{"key":"1102_CR32","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1093\/infdis\/jir834","volume":"205","author":"AV Barochia","year":"2012","unstructured":"Barochia AV, Cui X, Sun J, Li Y, Solomon SB, Migone TS, Subramanian GM, Bolmer SD, Eichacker PQ: Protective antigen antibody augments hemodynamic support in anthrax lethal toxin shock in canines. J Infect Dis. 2012, 205: 818-829. 10.1093\/infdis\/jir834.","journal-title":"J Infect Dis"},{"key":"1102_CR33","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1111\/j.1462-5822.2010.01438.x","volume":"12","author":"M Rolando","year":"2010","unstructured":"Rolando M, Stefani C, Flatau G, Auberger P, Mettouchi A, Mhlanga M, Rapp U, Galmiche A, Lemichez E: Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity. Cell Microbiol. 2010, 12: 891-905. 10.1111\/j.1462-5822.2010.01438.x.","journal-title":"Cell Microbiol"},{"key":"1102_CR34","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.3390\/toxins3101278","volume":"3","author":"JM Warfel","year":"2011","unstructured":"Warfel JM, D'Agnillo F: Anthrax lethal toxin-mediated disruption of endothelial ve-cadherin is attenuated by inhibition of the rho-associated kinase pathway. Toxins. 2011, 3: 1278-1293. 10.3390\/toxins3101278.","journal-title":"Toxins"},{"key":"1102_CR35","doi-asserted-by":"publisher","first-page":"1438","DOI":"10.1002\/jcp.22859","volume":"227","author":"T Liu","year":"2012","unstructured":"Liu T, Milia E, Warburton RR, Hill NS, Gaestel M, Kayyali US: Anthrax lethal toxin disrupts the endothelial permeability barrier through blocking p38 signaling. J Cell Physiol. 2012, 227: 1438-1445. 10.1002\/jcp.22859.","journal-title":"J Cell Physiol"},{"key":"1102_CR36","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1038\/nature09446","volume":"467","author":"A Guichard","year":"2010","unstructured":"Guichard A, McGillivray SM, Cruz-Moreno B, van Sorge NM, Nizet V, Bier E: Anthrax toxins cooperatively inhibit endocytic recycling by the Rab11\/Sec15 exocyst. Nature. 2010, 467: 854-858. 10.1038\/nature09446.","journal-title":"Nature"},{"key":"1102_CR37","doi-asserted-by":"publisher","first-page":"H238","DOI":"10.1152\/ajpheart.00185.2013","volume":"305","author":"Y Li","year":"2013","unstructured":"Li Y, Cui X, Solomon SB, Remy K, Fitz Y, Eichacker PQ: B. anthracis edema toxin increases camp levels and inhibits phenylephrine stimulated contraction in a rat aortic ring model. Am J Physiol Heart Circ Physiol. 2013, 305: H238-250. 10.1152\/ajpheart.00185.2013.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"1102_CR38","doi-asserted-by":"publisher","first-page":"721","DOI":"10.3390\/toxins3060721","volume":"3","author":"WS Lawrence","year":"2011","unstructured":"Lawrence WS, Marshall JR, Zavala DL, Weaver LE, Baze WB, Moen ST, Whorton EB, Gourley RL, Peterson JW: Hemodynamic effects of anthrax toxins in the rabbit model and the cardiac pathology induced by lethal toxin. Toxins. 2011, 3: 721-736. 10.3390\/toxins3060721.","journal-title":"Toxins"},{"key":"1102_CR39","doi-asserted-by":"publisher","first-page":"e1000456","DOI":"10.1371\/journal.ppat.1000456","volume":"5","author":"M Moayeri","year":"2009","unstructured":"Moayeri M, Crown D, Dorward DW, Gardner D, Ward JM, Li Y, Cui X, Eichacker P, Leppla SH: The heart is an early target of anthrax lethal toxin in mice: A protective role for neuronal nitric oxide synthase (nNos). PLoS Pathog. 2009, 5: e1000456-10.1371\/journal.ppat.1000456.","journal-title":"PLoS Pathog"},{"key":"1102_CR40","doi-asserted-by":"publisher","first-page":"e13335","DOI":"10.1371\/journal.pone.0013335","volume":"5","author":"MR Kandadi","year":"2010","unstructured":"Kandadi MR, Hua Y, Ma H, Li Q, Kuo SR, Frankel AE, Ren J: Anthrax lethal toxin suppresses murine cardiomyocyte contractile function and intracellular Ca2+ handling via a NADPH oxidase-dependent mechanism. PloS one. 2010, 5: e13335-10.1371\/journal.pone.0013335.","journal-title":"PloS one"},{"key":"1102_CR41","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/1741-7015-10-134","volume":"10","author":"MR Kandadi","year":"2012","unstructured":"Kandadi MR, Yu X, Frankel AE, Ren J: Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy. BMC Med. 2012, 10: 134-10.1186\/1741-7015-10-134.","journal-title":"BMC Med"},{"key":"1102_CR42","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1111\/j.1476-5381.2012.02040.x","volume":"167","author":"MR Kandadi","year":"2012","unstructured":"Kandadi MR, Frankel AE, Ren J: Toll-like receptor 4 knockout protects against anthrax lethal toxin-induced cardiac contractile dysfunction: role of autophagy. Br J Pharmacol. 2012, 167: 612-626. 10.1111\/j.1476-5381.2012.02040.x.","journal-title":"Br J Pharmacol"},{"key":"1102_CR43","doi-asserted-by":"publisher","first-page":"H1108","DOI":"10.1152\/ajpheart.01128.2010","volume":"300","author":"CW Hicks","year":"2011","unstructured":"Hicks CW, Li Y, Okugawa S, Solomon SB, Moayeri M, Leppla SH, Mohanty A, Subramanian GM, Mignone TS, Fitz Y, Cui X, Eichacker PQ: Anthrax edema toxin has cAMP-mediated stimulatory effects and high-dose lethal toxin has depressant effects in an isolated perfused rat heart model. Am J Physiol Heart Circ Physiol. 2011, 300: H1108-1118. 10.1152\/ajpheart.01128.2010.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"1102_CR44","doi-asserted-by":"publisher","first-page":"3693","DOI":"10.1128\/IAI.00709-13","volume":"81","author":"S Barua","year":"2013","unstructured":"Barua S, Iyer JK, Larabee JL, Raisley B, Hughes MA, Coggeshall KM, Ballard JD: Toxin inhibition of antimicrobial factors induced byB acillus anthracispeptidoglycan in human blood. Infect Immun. 2013, 81: 3693-3702. 10.1128\/IAI.00709-13.","journal-title":"Infect Immun"},{"key":"1102_CR45","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1093\/cid\/cis017","volume":"54","author":"AW Artenstein","year":"2012","unstructured":"Artenstein AW, Opal SM: Novel approaches to the treatment of systemic anthrax. Clin Infect Dis. 2012, 54: 1148-1161. 10.1093\/cid\/cis017.","journal-title":"Clin Infect Dis"},{"key":"1102_CR46","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1016\/j.bcp.2009.11.023","volume":"79","author":"B Raymond","year":"2010","unstructured":"Raymond B, Ravaux L, Memet S, Wu Y, Sturny-Leclere A, Leduc D, Denoyelle C, Goossens PL, Paya M, Raymondjean M, Touqui L: Anthrax lethal toxin down-regulates type-IIa secreted phospholipase a(2) expression through MAPK\/NF-kappaB inactivation. Biochem Pharmacol. 2010, 79: 1149-1155. 10.1016\/j.bcp.2009.11.023.","journal-title":"Biochem Pharmacol"},{"key":"1102_CR47","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.immuni.2011.04.015","volume":"35","author":"SR Ali","year":"2011","unstructured":"Ali SR, Timmer AM, Bilgrami S, Park EJ, Eckmann L, Nizet V, Karin M: Anthrax toxin induces macrophage death by p38 MAPK inhibition but leads to inflammasome activation via ATP leakage. Immunity. 2011, 35: 34-44. 10.1016\/j.immuni.2011.04.015.","journal-title":"Immunity"},{"key":"1102_CR48","doi-asserted-by":"publisher","first-page":"e14289","DOI":"10.1371\/journal.pone.0014289","volume":"5","author":"JH Kau","year":"2010","unstructured":"Kau JH, Sun DS, Huang HS, Lien TS, Huang HH, Lin HC, Chang HH: Sublethal doses of anthrax lethal toxin on the suppression of macrophage phagocytosis. PLoS One. 2010, 5: e14289-10.1371\/journal.pone.0014289.","journal-title":"PLoS One"},{"key":"1102_CR49","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.chom.2011.09.014","volume":"10","author":"MP Maddugoda","year":"2011","unstructured":"Maddugoda MP, Stefani C, Gonzalez-Rodriguez D, Saarikangas J, Torrino S, Janel S, Munro P, Doye A, Prodon F, Aurrand-Lions M, Goossens PL, Lafont F, Bassereau P, Lappalainen P, Brochard F, Lemichez E: cAMP signaling by anthrax edema toxin induces transendothelial cell tunnels, which are resealed by MIM via Arp2\/3-driven actin polymerization. Cell Host Microbe. 2011, 10: 464-474. 10.1016\/j.chom.2011.09.014.","journal-title":"Cell Host Microbe"},{"key":"1102_CR50","doi-asserted-by":"publisher","first-page":"2510","DOI":"10.1128\/IAI.00006-11","volume":"79","author":"CM Ebrahimi","year":"2011","unstructured":"Ebrahimi CM, Sheen TR, Renken CW, Gottlieb RA, Doran KS: Contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitis. Infect Immun. 2011, 79: 2510-2518. 10.1128\/IAI.00006-11.","journal-title":"Infect Immun"},{"key":"1102_CR51","doi-asserted-by":"publisher","first-page":"L117","DOI":"10.1152\/ajplung.00417.2009","volume":"301","author":"SL Sayner","year":"2011","unstructured":"Sayner SL, Balczon R, Frank DW, Cooper DM, Stevens T: Filamin A is a phosphorylation target of membrane but not cytosolic adenylyl cyclase activity. Am J Physiol Lung Cell Mol Physiol. 2011, 301: L117-124. 10.1152\/ajplung.00417.2009.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"1102_CR52","doi-asserted-by":"publisher","first-page":"L667","DOI":"10.1152\/ajplung.00433.2010","volume":"300","author":"SL Sayner","year":"2011","unstructured":"Sayner SL: Emerging themes of camp regulation of the pulmonary endothelial barrier. Am J Physiol Lung Cell Mol Physiol. 2011, 300: L667-678. 10.1152\/ajplung.00433.2010.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"1102_CR53","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1471-2180-12-2","volume":"12","author":"C Nguyen","year":"2012","unstructured":"Nguyen C, Feng C, Zhan M, Cross AS, Goldblum SE: Bacillus anthracis-derived edema toxin (ET) counter-regulates movement of neutrophils and macromolecules through the endothelial paracellular pathway. BMC Microbiol. 2012, 12: 2-10.1186\/1471-2180-12-2.","journal-title":"BMC Microbiol"},{"key":"1102_CR54","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1007\/s00424-009-0747-y","volume":"459","author":"M Metrich","year":"2010","unstructured":"Metrich M, Berthouze M, Morel E, Crozatier B, Gomez AM, Lezoualc'h F: Role of the cAMP-binding protein Epac in cardiovascular physiology and pathophysiology. Pflugers Arch. 2010, 459: 535-546. 10.1007\/s00424-009-0747-y.","journal-title":"Pflugers Arch"},{"key":"1102_CR55","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s00018-011-0815-2","volume":"69","author":"M Morgado","year":"2012","unstructured":"Morgado M, Cairrao E, Santos-Silva AJ, Verde I: Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle. Cell Mol Life Sci. 2012, 69: 247-266. 10.1007\/s00018-011-0815-2.","journal-title":"Cell Mol Life Sci"},{"key":"1102_CR56","doi-asserted-by":"publisher","first-page":"3242","DOI":"10.1073\/pnas.0306552101","volume":"101","author":"Y Shen","year":"2004","unstructured":"Shen Y, Zhukovskaya NL, Zimmer MI, Soelaiman S, Bergson P, Wang CR, Gibbs CS, Tang WJ: Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis b virus infection. Proc Natl Acad Sci U S A. 2004, 101: 3242-3247. 10.1073\/pnas.0306552101.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1102_CR57","doi-asserted-by":"publisher","first-page":"580","DOI":"10.3390\/toxins4080580","volume":"4","author":"E Laine","year":"2012","unstructured":"Laine E, Martinez L, Ladant D, Malliavin T, Blondel A: Molecular motions as a drug target: mechanistic simulations of anthrax toxin edema factor function led to the discovery of novel allosteric inhibitors. Toxins. 2012, 4: 580-604. 10.3390\/toxins4080580.","journal-title":"Toxins"},{"key":"1102_CR58","doi-asserted-by":"publisher","first-page":"3302","DOI":"10.1128\/IAI.05070-11","volume":"79","author":"JL Larabee","year":"2011","unstructured":"Larabee JL, Maldonado-Arocho FJ, Pacheco S, France B, DeGiusti K, Shakir SM, Bradley KA, Ballard JD: Glycogen synthase kinase 3 activation is important for anthrax edema toxin-induced dendritic cell maturation and anthrax toxin receptor 2 expression in macrophages. Infect Immun. 2011, 79: 3302-3308. 10.1128\/IAI.05070-11.","journal-title":"Infect Immun"},{"key":"1102_CR59","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/j.1747-0285.2008.00757.x","volume":"73","author":"OA Adekoya","year":"2009","unstructured":"Adekoya OA, Sylte I: The thermolysin family (M4) of enzymes: therapeutic and biotechnological potential. Chem Biol Drug Des. 2009, 73: 7-16. 10.1111\/j.1747-0285.2008.00757.x.","journal-title":"Chem Biol Drug Des"},{"key":"1102_CR60","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1471-2334-5-25","volume":"5","author":"SG Popov","year":"2005","unstructured":"Popov SG, Popova TG, Hopkins S, Weinstein RS, MacAfee R, Fryxell KJ, Chandhoke V, Bailey C, Alibek K: Effective antiprotease-antibiotic treatment of experimental anthrax. BMC Infect Dis. 2005, 5: 25-10.1186\/1471-2334-5-25.","journal-title":"BMC Infect Dis"},{"key":"1102_CR61","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1111\/j.1574-695X.2011.00798.x","volume":"62","author":"MC Chung","year":"2011","unstructured":"Chung MC, Jorgensen SC, Tonry JH, Kashanchi F, Bailey C, Popov S: Secreted Bacillus anthracis proteases target the host fibrinolytic system. FEMS Immunol Med Microbiol. 2011, 62: 173-181. 10.1111\/j.1574-695X.2011.00798.x.","journal-title":"FEMS Immunol Med Microbiol"},{"key":"1102_CR62","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1099\/jmm.0.007427-0","volume":"58","author":"MC Chung","year":"2009","unstructured":"Chung MC, Jorgensen SC, Popova TG, Tonry JH, Bailey CL, Popov SG: Activation of plasminogen activator inhibitor implicates protease InhA in the acute-phase response to Bacillus anthracis infection. J Med Microbiol. 2009, 58: 737-744. 10.1099\/jmm.0.007427-0.","journal-title":"J Med Microbiol"},{"key":"1102_CR63","doi-asserted-by":"publisher","first-page":"9531","DOI":"10.1074\/jbc.M705871200","volume":"283","author":"MC Chung","year":"2008","unstructured":"Chung MC, Popova TG, Jorgensen SC, Dong L, Chandhoke V, Bailey CL, Popov SG: Degradation of circulating von Willebrand factor and its regulator ADAMTS13 implicates secreted Bacillus anthracis metalloproteases in anthrax consumptive coagulopathy. J Biol Chem. 2008, 283: 9531-9542. 10.1074\/jbc.M705871200.","journal-title":"J Biol Chem"},{"key":"1102_CR64","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/j.1574-695X.2008.00480.x","volume":"54","author":"MC Chung","year":"2008","unstructured":"Chung MC, Jorgensen SC, Popova TG, Bailey CL, Popov SG: Neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax. FEMS Immunol Med Microbiol. 2008, 54: 309-318. 10.1111\/j.1574-695X.2008.00480.x.","journal-title":"FEMS Immunol Med Microbiol"},{"key":"1102_CR65","doi-asserted-by":"publisher","first-page":"e17921","DOI":"10.1371\/journal.pone.0017921","volume":"6","author":"DV Mukherjee","year":"2011","unstructured":"Mukherjee DV, Tonry JH, Kim KS, Ramarao N, Popova TG, Bailey C, Popov S, Chung MC: Bacillus anthracis protease InhA increases blood?brain barrier permeability and contributes to cerebral hemorrhages. PLoS One. 2011, 6: e17921-10.1371\/journal.pone.0017921.","journal-title":"PLoS One"}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1741-7015-11-217.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/1741-7015-11-217\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1741-7015-11-217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1741-7015-11-217.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T20:05:59Z","timestamp":1630613159000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedicine.biomedcentral.com\/articles\/10.1186\/1741-7015-11-217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,9]]},"references-count":65,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["1102"],"URL":"https:\/\/doi.org\/10.1186\/1741-7015-11-217","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,9]]},"assertion":[{"value":"11 December 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"217"}}