Novel approaches to the treatment of systemic anthrax

Clinical Infectious Diseases

Volumn 54, Issue 8, 2012, Pages 1148-1161

  Artenstein, Andrew W ^a,b   Opal, Steven M ^a,b  

^a MEMORIAL HOSPITAL OF RHODE ISLAND   (United States)

^b BROWN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCYSTEINE; ADEFOVIR; AMIODARONE; AMPICILLIN; ANTIINFECTIVE AGENT; ANTITOXIN; CARBAPENEM; CELECOXIB; CHLORAMPHENICOL; CHLOROQUINE; CISPLATIN; CLINDAMYCIN; CROMOGLYCATE DISODIUM; DOXYCYCLINE; EXOTOXIN; FLUINDOSTATIN; INDOMETACIN; KETOTIFEN; MEPACRINE; NEOMYCIN; NICLOSAMIDE; NIFEDIPINE; PENICILLIN G; PROTAMINE; QUINIDINE; QUINOLONE; RIFAMPICIN; UNINDEXED DRUG; VANCOMYCIN; VERAPAMIL;

ADAPTIVE IMMUNITY; ANTHRAX; BIOLOGICAL WARFARE; CELL CULTURE; CELL PROLIFERATION; CLINICAL TRIAL (TOPIC); DENDRITIC CELL; DISEASE ASSOCIATION; DRUG ACTIVITY; DRUG BINDING; ENDOCYTOSIS; EPIDEMIC; GENETIC TRANSCRIPTION; HEART ARRHYTHMIA; HUMAN; LYMPHOCYTE; MACROPHAGE; MORTALITY; MUTANT; NONHUMAN; PASSIVE IMMUNIZATION; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN PROCESSING; REVIEW; SALVAGE THERAPY; VIRULENCE;

ANTHRAX; ANTI-INFECTIVE AGENTS; ANTITOXINS; HUMANS; IMMUNOTHERAPY;

EID: 84859046620     PISSN: 10584838     EISSN: 15376591     Source Type: Journal    
DOI: 10.1093/cid/cis017     Document Type: Review

References (129)

1. Turnbull PC. Anthrax. In: Artenstein AW, ed. Vaccines: a biography. New York, NY: Springer, 2009: 57-71.
2. Holty JE, Bravat DM, Liu H, Olshen RA, McDonald KM, Owens DK. Systematic review: a century of inhalational anthrax cases from 1900 to 2005. Ann Intern Med 2006; 144:270-80.
3. Inglesby TV, O'Toole T, Henderson DA, et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002; 287:2236-52.
4. Ringertz SH, Høiby EA, Jensenius M, et al. Injectional anthrax in a heroin skin-popper. Lancet 2000; 356:1574-5.
5. Ramsay CN, Stirling A, Smith J, et al. An outbreak of infection with Bacillus anthracis in injecting drug users in Scotland. Euro Surveill 2010; 15:pii 19465. Available at: http://www.Eurosurveillance.org.
6. Powell AG, Crozier JE, Hodgson H, Galloway DJ. A case of septicemic anthrax in an intravenous drug user. BMC Infect Dis 2011; 11:21; doi:10.1186/1471-2334-11-21.
7. Radun D, Bernard H, Altmann M, et al. Preliminary case report of fatal anthrax in an injecting drug user in North-Rhine-Westphalia, Germany, December 2009. Euro Surveill 2010; 15:pii 19464. Available at: http://www. Eurosurveillance.org.
8. Bhatnagar R, Friedlander AM. Protein synthesis is required for expression of anthrax lethal toxin cytotoxicity. Infect Immun 1994; 62: 2958-62.
9. Lappin E, Ferguson AJ. Gram-positive toxic shock syndromes. Lancet Infect Dis 2009; 9:281-90.
10. Brook I, Germana A, Giraldo DE, et al. Clindamycin and quinolone therapy for Bacillus anthracis Sterne infection in 60Co-gamma-photonirradiated and sham-irradiated mice. J Antimicrob Chemother 2005; 56:1074-80.
11. Artenstein AW. Anthrax: from antiquity to answers. J Infect Dis 2007; 195:471-3.
12. Spencer RC. Bacillus anthracis. J Clin Path 2003; 56:182-7.
13. Brossier F, Levy M, Mock M. Anthrax spores make an essential contribution to vaccine efficacy. Infect Immun 2002; 70:661-4.
14. Chakrabarty K, Wu W, Booth JL, Duggan ES, Coggeshall KM, Metcalf JP. Bacillus anthracis spores stimulate cytokine and chemokine innate immune responses in human alveolar macrophages through multiple mitogen-activated protein kinase pathways. Infect Immun 2006; 74:4430-8.
15. Pickering AK, Osorio M, Lee GM, Grippe VK, Bray M, Merkel TJ. Cytokine response to infection with Bacillus anthracis spores. Infect Immun 2004; 72:6382-9.
16. Wilson AC, Soyer M, Hoch JA, Parego M. The bicarbonate transporter is essential for Bacillus anthracis lethality. PLoS Pathogens 2008; 4:1-9.
17. Jones MB, Blaser MJ. Detection of a luxS-signaling molecule in Bacillus anthracis. Infection 2003; 71:39-49.
18. Jones MB, Jani R, Ren D, Wood TK, Blaser MJ. Inhibition of Bacillus anthracis growth and virulence-gene expression by inhibitors of quorum-sensing. J Infect Dis 2005; 191:1881-8.
19. Read TD, Peterson SN, Tourassa N, et al. The genome sequence of Bacillus anthracis Ames and comparison with closely related bacteria. Nature 2003; 423:81-8.
20. Jang J, Cho M, Chun JH, et al. The poly-c-D-glutamic acid capsule of Bacillus anthracis enhances lethal toxin. Infect Immun 2011; 79: 3846-54.
21. Piris-Gimenez A, Corre JP, Jouvion G, Candela T, Khun H. Encapsulated Bacillus anthracis interacts closely with liver endothelium. J Infect Dis 2009; 200:1381-9.
22. Terra JK, Cote CK, France B, et al. Cutting edge: resistance to Bacillus anthracis infection mediated by a lethal toxin sensitive allele of NaLp1b/NIrp1b. J Immunol 2010; 184:17-20.
23. Newman ZL, Sirianni N, Mawhinney C, et al. Auranofin protects against anthrax lethal toxin-induced activation of the NIrp1b inflammasome. Antimicrob Agents Chemother 2011; 55:1028-35.
24. Agrawal A, Lingappa J, Leppla SH, et al. Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin. Nature 2003; 424: 329-34.
25. Comer JE, Chopra AK, Peterson JW, Konig R. Direct inhibition of T-lymphocyte activation by anthrax toxins in vivo. Infect Immun 2005; 73:8275-81.
26. Fang H, Xu L, Chen TY, Cyr JM, Frucht DM. Anthrax lethal toxin has direct and potent inhibitory effects on B cell proliferation and immunoglobulin production. J Immunol 2006; 176:6155-61.
27. Baldari CT, Tonello F, Pacani SR, Montecucco C. Anthrax toxins: a paradigm of bacterial immune suppression. Trends Immunol 2006; 27:434-40.
28. During RI, Li W, Hao B, et al. Anthrax lethal toxin paralyzes neutrophil actin-based mobility. J Infect Dis 2005; 192:837-45.
29. Kandadi MR, Hua Y, Ma H, et al. Anthrax lethal toxin suppresses murine cardiomyocyte contractile function and intracellular Ca21 handling via a NADPH oxidase-dependent mechanism. PLoS One 2010; 5:e1335; doi: 10.1371/journal.pone. 0013335.
30. Cui X, Li Y, Li X, et al. Bacillus anthracis edema and lethal toxin have different hemodynamic effects but function together to worsen shock and outcome in a rat model. J Infect Dis 2007; 195:572-80.
31. Sweeney DA, Cui Z, Solomon SB, et al. Anthrax lethal and edema toxins produce different patterns of cardiovascular and renal dysfunction and synergistically decrease survival in canines. J Infect Dis 2010; 202:1885-96.
32. Cui X, Moayeri M, Li Y, et al. Lethality during continuous anthrax lethal toxin infusion is associated with circulatory shock but not inflammatory cytokine or nitric oxide release in rats. Am J Physiol Regul Integr Comp Physiol 2004; 286:R699-709.
33. Erwin JL, DaSilva LM, Bavari S, Little SF, Friedlander AM, Chanh TC. Macrophage-derived cell lines do not express proinflammatory cytokines after exposure to Bacillus anthracis lethal toxin. Infect Immun 2001; 69:1175-7.
34. Kim SO, Qing J, Hoebe K, Beutler B, Duesbery NS. Sensitizing anthrax lethal toxin-resistant macrophages to lethal toxin-induced killing by tumor necrosis factor-alpha. J Biol Chem 2003; 278:7413-21.
35. Levy H, Weiss S, Altboum Z, et al. Lethal factor is not required for Bacillus anthracis virulence in guinea pigs and rabbits. Microb Pathog 2011; 51:345-51.
36. Leppla SH. Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations in eukaryotic cells. Proc Natl Acad Sci USA 1982; 79:3162-6.
37. Hicks CW, Li Y, Okugawa S, et al. Anthrax edema toxin has cAMPmediated stimulatory effects and high-dose lethal toxin has depressant effects in an isolated perfused rat heart model. Am J Physiol Heart Circ Physiol 2010; 300:H1108-18.
38. Hoover DL, Friedlander AM, Rogers LC, Yoon I-K, Warren RL, Cross AS. Anthrax edema toxin differentially regulates lipopolysaccharideinduced monocyte production of tumor necrosis factor alpha and interleukin-6 by increasing intracellular cyclic AMP. Infect Immun 1994; 62:4432-9.
39. O'Brien J, Friedlander A, Dreier T, Ezzell J, Leppla S. Effects of anthrax toxin components on human neutrophils. Infect Immun 1985; 47:306-10.
40. Crawford MA, Aylott CV, Bordeau RW, Bokoch GM. Bacillus anthracis toxins inhibit human neutrophil NADPH oxidase activity. J Immunol 2006; 176:7557-65.
41. Kim C, Wilcox-Adelman S, Sano Y, Tang WJ, Collier RJ, Park JM. Anti-inflammatory cAMP signaling and cell migration genes co-opted by the anthrax bacillus. Proc Natl Acad Sci USA 2008; 105:6150-5.
42. Watson LE, Mock J, Lal H, et al. Lethal and edema toxins of anthrax induce distinct hemodynamic dysfunction. Front Biosci 2007; 12: 4670-5.
43. Triantafilou M, Uddin A, Maher S, et al. Anthrax toxin evades Tolllike receptor recognition, whereas its cell wall components trigger activation via TLR2/6 heterodimers. Cell Microbiol 2007; 9:2880-92.
44. Young JA, Collier RJ. Anthrax toxin: receptor binding, internalization, pore formation, and translocation. Annu Rev Biochem 2007; 76: 243-65.
45. Bradley KA, Mogridge J, Mourez M, Collier RJ, Young JA. Identification of the cellular receptor for anthrax toxin. Nature 2001; 414:225.
46. Liu S, Leppla SH. Cell surface tumor endothelium marker 8 cytoplasmic tail-independent anthrax toxin binding, proteolytic processing, oligomer formation, and internalization. J Biol Chem 2003; 278:5227-34.
47. Verma K, Gu J, Werner E. Tumor endothelial marker 8 amplifies canonical Wnt signaling in blood vessels. PLoS One 2011; 6:e22334; doi: 10.1371/journal.pone.0022334.
48. Scobie HM, Rainey GJ, Bradley KA, Young JA. Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc Natl Acad Sci USA 2003; 100:5170-4.
49. Klimpel KR, Molloy SS, Thomas G, Leppla SH. Anthrax toxin protective antigen is activated by a cell surface protease with the sequence specificity and catalytic properties of furin. Proc Natl Acad Sci USA 1992; 89:10277-81.
50. Gordon VM, Rehemtulla A, Leppla SH. A role for PACE4 in the proteolytic activation of anthrax toxin protective antigen. Infect Immun 1997; 65:3370-5.
51. Kintzer AF, Thoren KL, Sterling HJ, et al. The protective antigen component of anthrax toxin forms functional octameric complexes. J Mol Biol 2009; 392:614-2.
52. Petosa C, Collier RJ, Klimpel KR, Leppla SH, Liddington RC. Crystal structure of the anthrax toxin protective antigen. Nature 1997; 385:833-8.
53. Wei W, Lu Q, Chaudry GJ, Leppla SH, Cohen SN. The LDL receptorrelated protein LRP6 mediates internalization and lethality of anthrax toxin. Cell 2006; 126:1141-54.
54. Young JJ, Bromberg-White JL, Zylstra C, et al. LRP5 and LRP6 are not required for protective antigen-mediated internalization or lethality of anthrax lethal toxin. PLoS Pathog 2007; 3:e27.
55. Rainey GJ, Wigelsworth DJ, Ryan PL, Scobie HM, Collier RJ, Young JA. Receptor-specific requirements for anthrax toxin delivery into cells. Proc Natl Acad Sci USA 2005; 102:13278-83.
56. Sun J, Vernier G, Wigelsworth DJ, Collier RJ. Insertion of anthrax protective antigen into liposomal membranes: effects of a receptor. J Biol Chem 2007; 282:1059-65.
57. Brown MJ, Thoren KL, Krantz BA. Charge requirements for proton gradient-driven translocation of anthrax toxin. J Biol Chem 2011; 286:23189-99.
58. Zhang S, Udho E,Wu Z, Collier RJ, Finkelstein A. Protein translocation through anthrax toxin channels formed in planar lipid bilayers. Biophys J 2004; 87:3842-9.
59. Pannifer AD, Wong TY, Schwarzenbacher R, et al. Crystal structure of the anthrax lethal factor. Nature 2001; 414:229-33.
60. Duesbery NS, Webb CP, Leppla SH, et al. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 1998; 280: 734-7.
61. Vitale G, Pellizzari R, Recchi C, Napolitani G, Mock M, Montecucco C. Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem Biophys Res Comm 1998; 248:706-11.
62. Jernigan JA, Stephens DS, Ashford DA, et al. Boterrorism-related inhalational anthrax: the first 10 cases reported in the United States. Emerg Infect Dis 2001; 7:933-44.
63. Department of Health and Human Services, Food and Drug Administration. New drug and biological drug products; evidence needed to demonstrate effectiveness of new drugs when human efficacy studies are not ethical or feasible. Fed Regist 2002; 67:37988-98.
64. Sherer K, Li Y, Cui X, et al. Fluid support worsens outcome and negates the benefit of protective antigen-directed monoclonal antibody in a lethal toxin-infused rat Bacillus anthracis shock model. Crit Care Med 2007; 35:1560-7.
65. Li Y, Cui X, Su J, et al. Norepinephrine increases blood pressure but not survival with anthrax lethal toxin in rats. Crit Care Med 2009; 37: 1348-54.
66. Moayeri M, Webster JI, Wiggins JF, Leppla SH, Sternberg EM. Endocrine perturbation increases susceptibility of mice to anthrax lethal toxin. Infect Immun 2005; 73:4238-44.
67. Cangene Corporation. Biodefense Products, 2009. Available at: www. cangene.com/biodefense-products.shtml. Accessed 2 February 2012.
68. Walsh JJ, Pesik N, Quinn CP, et al. A case of naturally acquired inhalational anthrax: clinical care and analyses of anti-protective antigen immunoglobulin G and lethal factor. Clin Infect Dis 2007; 44: 968-71.
69. National Services Scotland, Health Protection Scotland. Clinical Guidelines for use of anthrax immune globulin intravenous (human) (AIGIV) in Scotland. Available at: www.hps.scot.nhs.uk/anthrax/documents/guidelines- anthrax-immune-globulin-v3-2010-02-08.pdf. Accessed 2 February 2012.
70. Wright JG, Quinn CP, Shadomy S, Messonnier N. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep 2010; 59:1-30.
71. Little SF, Ivins BE, Fellows PF, Pitt ML, Norris SL, Andrews GP. Defining a serological correlate of protection in rabbits for a recombinant anthrax vaccine. Vaccine 2004; 22:422-30.
72. Little SF, Ivins BE, Fellows PF, Friedlander AM. Passive protection by polyclonal antibodies against Bacillus anthracis infection in guinea pigs. Infect Immun 1997; 65:5171-5.
73. Berry JD, Gaudet RG. Antibodies in infectious diseases: polyclonals, monoclonals and niche biotechnology. N Biotechnol 2011; 28:489-501.
74. Maynard JA, Maassen CB, Leppla SH, et al. Protection against anthrax toxin by recombinant antibody fragments correlates with antigen affinity. Nat Biotechnol 2002; 20:597-601.
75. Wild MA, Xin H, Maruyama T, et al. Human antibodies from immunized donors are protective against anthrax toxin in vivo. Nat Biotechnol 2003; 21:1305-6.
76. Sawada-Hirai R, Jiang I, Wang F, et al. Human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed. J Immune Based Ther Vaccines 2004; 2:5; doi: 10.1186/1476-8518-2-5.
77. Mohamed N, Clagett M, Li J, et al. A high-affinity monoclonal antibody to anthrax protective antigen passively protects rabbits before and after aerosolized Bacillus anthracis spore challenge. Infect Immun 2005; 73:795-802.
78. Schneemann A, Manchester M. Anti-toxin antibodies in prophylaxis and treatment of inhalational anthrax. Future Microbiol 2009; 4:35-43.
79. Subramanian GM, Cronin PW, Poley G, et al. A phase I study of PA mAb, a fully human monoclonal antibody against Bacillus anthracis protective antigen, in healthy volunteers. Clin Infect Dis 2005; 41:12-20.
80. Migone TS, Subramanian GM, Zhong J, et al. Raxibacumab for the treatment of inhalational anthrax. N Engl J Med 2009; 361:135-44.
81. Cui X, Li Y, Moayeri M, et al. Late treatment with a protective antigen-directed monoclonal antibody improves hemodynamic function and survival in a lethal toxin-infused rat model of anthrax sepsis. J Infect Dis 2005; 191:422-34.
82. Albrecht MT, Li H, Williamson ED, et al. Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against Bacillus anthracis infection and enhance endogenous immunity to anthrax. Infect Immun 2007; 75:5425-33.
83. Chen Z, Moayeri M, Crown D, et al. Novel chimpanzee/human monoclonal antibodies that neutralize anthrax lethal factor, and evidence for possible synergy with anti-protective antigen antibody. Infect Immun 2009; 77:3902-8.
84. Chen Z, Moayeri M, Zhao H, Crown D, Leppla SH, Purcell RH. Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding. Proc Natl Acad Sci USA 2009; 106:13487-92.
85. Wycoff KL, Belle A, Deppe D, et al. Recombinant anthrax toxin receptor-Fc fusion proteins produced in plants protect rabbits against inhalational anthrax. Antimicrob Agents Chemother 2011; 55:132-9.
86. Chen Z, Schneerson R, Lovchik J, et al. Pre-and postexposure protection against virulent anthrax infection in mice by humanized monoclonal antibodies to Bacillus anthracis capsule. Proc Natl Acad Sci USA 2011; 108:739-44.
87. Sanchez AM, Thomas D, Gillespie EJ, et al. Amiodarone and bepridil inhibit anthrax toxin entry into host cells. Antimicrob Agents Chemother 2007; 51:2403-11.
88. Artenstein AW, Opal SM, Cristofaro P, et al. Chloroquine enhances survival in Bacillus anthracis intoxication. J Infect Dis 2004; 190:1655-60.
89. Hanna PC, Kruskal BA, Ezekowitz RA, Bloom BR, Collier RJ. Role of macrophage oxidative burst in the action of anthrax lethal toxin. Mol Med 1994; 1:7-18.
90. Zhu PJ, Hobson P, Southall N, et al. Quantitative high throughput screening identifies inhibitors of anthrax-induced cell death. Biorg Med Chem 2009; 17:5139-45.
91. Newman ZL, Crown D, Leppla SH, Moayeri M. Anthrax lethal toxin activates the inflammasome in sensitive rat macrophages. Biochem Biophys Res Commun 2010; 398:785-9.
92. Bhatnagar R, Singh Y, Leppla SH, Friedlander AM. Calcium is required for the expression of anthrax lethal toxin activity in the macrophage like cell line J774A.1. Infect Immun 1989; 57:2107-14.
93. Kumar P, Ahuja N, Bhatnagar R. Anthrax edema toxin requires influx of calcium for inducing cyclic AMP toxicity in target cells. Infect Immun 2002; 70:4997-5007.
94. GoldmanME, Cregar L, Nguyen D, Simo O,O'Malley S, Humphreys T. Cationic polyamines inhibit anthrax lethal factor protease. BMC Pharmacol 2006; 6:8, doi:10.1186/1471-2210-6-8.
95. Thomas M, Castignetti D. Examination of anthrax lethal factor inhibition by siderophores, small hydroxamates, and protamine. J Microbiol Immunol Infect 2009; 42:284-9.
96. deCathelineau AM, Bokoch GM. Inactivation of Rho GTPases by statins attenuates anthrax lethal toxin activity. Infect Immun 2009; 77: 348-59.
97. Tessier J, Green C, Padgett D, et al. Contributions of histamine, prostanoids, and neurokinins to edema elicited by edema toxin from Bacillus anthracis. Infect Immun 2007; 75:1895-903.
98. Gozes Y, Moayeri M, Wiggins JF, Leppla SH. Anthrax lethal toxin induces ketotifen-sensitive intradermal vascular leakage in certain inbred mice. Infect Immun 2006; 74:1266-72.
99. Moayeri M, Wiggins JF, Lindeman RE, Leppla SH. Cisplatin inhibition of anthrax lethal toxin. Antimicrob Agents Chemother 2006; 50:2658-65.
100. Shen Y, Zhukovskaya NL, Zimmer MI, et al. Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B infections. Proc Natl Acad Sci USA 2004; 101:3242-7.
101. Shin S, Kim YB, Hur GH. Involvement of phospholipase A2 activation in anthrax lethal toxin-induced cytotoxicity. Cell Biol Toxicol 1999; 15:19-29.
102. Shin S, Hur GH, Kim YB, Park KJ, Less WS. Intracellular calcium antagonist protects cultured peritoneal macrophages against anthrax lethal toxin-induced cytotoxicity. Cell Biol Toxicol 2000; 16:137-44.
103. Hirsh MI, Cohen V. Chloroquine prevents T lymphocyte suppression induced by anthrax lethal toxin. J Infect Dis 2006; 194:1003-7.
104. Komiyama T, Swanson JA, Fuller RS. Protection from anthrax toxinmediated killing of macrophages by the combined effects of furin inhibitors and chloroquine. Antimicrob Agents Chemother 2005; 49: 3875-82.
105. Welkos S, Friedlander A, Weeks S, Little S, Mendelson I. In-vitro characterization of the phagocytosis and fate of anthrax spores in macrophages and the effects of anti-PA antibody. J Med Microbiol 2002; 51:821-31.
106. Kocer SS,Walker SG, Zerler B, Golub LM, Simon SR.Metalloproteinase inhibitors, nonantimicrobial chemically modified tetracyclines, and ilomastat block Bacillus anthracis lethal factor activity in viable cells. Infect Immun 2005; 73:7548-57.
107. Dell'Aica I, Dona M, Tonello F, et al. Potent inhibitors of anthrax lethal factor from green tea. EMBO Rep 2004; 5:418-22.
108. Kau JH, Sun DS, Tsai WJ, et al. Antiplatelet activities of anthrax lethal toxin are associated with suppressed p42/44 and p38 mitogen-activated protein kinase pathways in the platelets. J Infect Dis 2005; 192:1465-74.
109. Turk BE. Discovery and development of anthrax lethal factor metalloproteinase inhibitors. Curr Pharm Biotech 2008; 9:24-33.
110. Artenstein AW, Opal SM. Proprotein convertases in health and disease. N Engl J Med 2011; 365:2507-18.
111. Molloy S, Bresnahan P, Leppla S, et al. Human furin is a calciumdependent serine endoprotease that recognizes the sequence Arg-X-XArg and efficiently cleaves anthrax toxin protective antigen. J Biol Chem 1992; 267:16396-402.
112. Opal SM, Artenstein AW, Cristofaro PA, et al. Inter-alpha-inhibitor proteins are endogenous furin inhibitors and provide protection against experimental anthrax intoxication. Infect Immun 2005; 73: 5101-5.
113. Opal SM, Lim YP, Siryaporn E, et al. Longitudinal studies of interalpha inhibitor proteins in severely septic patients: a potential clinical marker and mediator of severe sepsis. Crit Care Med 2007; 35:387-92.
114. Lim YP, Bendelja K, Opal SM, et al. Correlation between mortality and the levels of inter-alpha inhibitors in the plasma of patients with severe sepsis. J Infect Dis 2003; 188:919-26.
115. Ying Z, Chen H, Li YM, et al. Thymosin a1 and ulinastatin-based immunomodulatory strategy for sepsis arising from intra-abdominal infection due to carbapenem-resistant bacteria. J Infect Dis 2008; 198: 723-30.
116. Opal SM, Lim YP, Cristofaro P, et al. Inter-alpha inhibitor proteins as a novel treatment strategy of systemic anthrax infection. Shock 2011; 35:42-4.
117. Jean F, Stella K, Thomas L, et al. Alpha antitrypsin Portland, a bioengineered serpin highly selective for furin: application as an antipathogenic agent. Proc Natl Acad Sci USA 1998; 95:7293-8.
118. Sellman BR, Mourez M, Collier RJ. Dominant-negative mutants of a toxin subunit: an approach to therapy of anthrax. Science 2001; 292:695-7.
119. Schuch R, Nelson D, Fischetti VA. A bacteriolytic agent that detects and kills Bacillus anthracis. Nature 2002; 418:884-9.
120. Fischetti VA. Bacteriophage lysins as effective antibacterials. Curr Opin Microbiol 2008; 11:393-400; doi:10.1016/j.mib.2008.09.012.
121. Asad S, Opal SM. Quorum sensing and the role of cell to cell communication in pathogenesis of invasive infection. Crit Care 2008; 12:236-45.
122. Mourez M, Kane RS, Mogridge J, et al. Designing a polyvalent inhibitor of anthrax toxin. Nat Biotechnol 2001; 19:958-61.
123. Akoachere M, Squires RC, Nour AM, Angelov L, Brojatsch J, Abel-Santos EV. Identification of an in vivo inhibitor of Bacillus anthracis spore germination. J Biol Chem 2007; 282:12112-8.
124. Wang W, Mulakala C, Ward SC, et al. Retrocyclins kill bacilli and germinating spores of Bacillus anthracis and inactivate anthrax lethal toxin. J Biol Chem 2006; 281:32755-64.
125. Crawford MA, Burdick MD, Glomski IJ, et al. Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection. PLoS Pathog 2010; 6:e1001199.
126. Crawford MA, Lowe DE, Fisher DJ, et al. Identification of the bacterial protein FtsX as a unique target of chemokine-mediated antimicrobial activity against Bacillus anthracis. Proc Natl Acad Sci USA 2011; 108: 12159-64.
127. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011; 117:3720-32.
128. Marshall JC, Dietch E, Moldawer LL, et al. Preclinical models of shock and sepsis: what do they tell us? Shock 2006; 24(Suppl 1):1-6.
129. Marshall J, Abraham E, Adikhari N, et al. InFACT: a global critical care research response to H1N1. Lancet 2010; 375:11-13.