Bacillus anthracis infections – new possibilities of treatment
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Biological Threats Identification and Countermeasure Centre, Military Institute of Hygiene and Epidemiology, Puławy, Poland
Warsaw Medical University, Department of Epidemiology, Institute of Social Medicine, Warsaw, Poland
Faculty of Chemistry and New Techonlogies, Military University of Technology, Warsaw, Poland
Military Institute of Hygiene and Epidemiology, Warsaw, Poland
Ann Agric Environ Med. 2015;22(2):202–207
Introduction and objective:
Bacillus anthracis is one of biological agents which may be used in bioterrorism attacks. The aim of this study a review of the new treatment possibilities of anthrax, with particular emphasis on the treatment of pulmonary anthrax.

Abbreviated description of the state of knowledge:
Pulmonary anthrax, as the most dangerous clinical form of the disease, is also extremely difficult to treat. Recently, considerable progress in finding new drugs and suitable therapy for anthrax has been achieved, for example, new antibiotics worth to mentioning, levofloxacin, daptomycin, gatifloxacin and dalbavancin. However, alternative therapeutic options should also be considered, among them the antimicrobial peptides, characterized by lack of inducible mechanisms of pathogen resistance. Very promising research considers bacteriophages lytic enzymes against selected bacteria species, including antibiotic-resistant strains.

Interesting results were obtained using monoclonal antibodies: raxibacumab, cAb29 or cocktails of antibodies. The application of CpG oligodeoxynucleotides to boost the immune response elicited by Anthrax Vaccine Adsorbed and CMG2 protein complexes, also produced satisfying therapy results. Furthermore, the IFN-α and IFN-β, PA-dominant negative mutant, human inter-alpha inhibitor proteins and LF inhibitors in combination with ciprofloxacin, also showed very promising results.

Recently, progress has been achieved in inhalation anthrax treatment. The most promising new possibilities include: new antibiotics, peptides and bacteriophages enzymes, monoclonal antibodies, antigen PA mutants, and inter alpha inhibitors applications. In the case of the possibility of bioterrorist attacks, the examination of inhalation anthrax treatment should be intensively continued.

Jernigan JA, Stephens DS, Ashford DA, Omenaca C, Topiel MS, Galbraith M, et al. Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. Emerg Infect Dis. 2001; 7(6): 933–944.
Brook I, Elliott TB, Pryor II HI, Sautter TE, Gnade BT, Thakar JH, et al. In vitro resistance of Bacillus anthracis Sterne to doxycycline, macrolides and quinolones. Int J Antimicrob Agents. 2001; 18: 559–562.
Athamna A, Athamna M, Abu-Rashed N, Medlej B, Bast DJ, Rubinstein E. Selection of Bacillus anthracis isolates resistant to antibiotics. J Antimicrob Chemother. 2004; 54: 424–428.
Brook I. The prophylaxis and treatment of anthrax. Int J Antimicrob Agents. 2002; 20: 320–325.
Żakowska D, Bartoszcze M, Niemcewicz M, Bielawska-Drózd A. Nowe możliwości hamowania infekcji B. anthracis. Medycyna Wet. 2011; 67(10): 665–668 (in Polish).
Żakowska D, Bartoszcze M, Niemcewicz M, Bielawska-Drózd A, Kocik J. New aspects of the infection mechanisms of Bacillus anthracis. Ann Agric Environ Med. 2012; 19(4): 613–618.
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.
Fowler RA, Shafazand S. Anthrax bioterrorism: prevention, diagnosis and management strategies. J Bioterr Biodef. 2011; 2: 107.
Wang JY, Roehrl MH. Anthrax vaccine design: strategies to achieve comprehensive protection against spore, bacillus, and toxin. Med Immunol. 2005; 4: 4.
Leffel EK, Bourdage JS, Williamson ED, Duchars M, Fuerst TR, Fusco PC. Recombinant protective antigen anthrax vaccine improves survival when administered as a postexposure prophylaxis countermeasure with antibiotic in the New Zealand white rabbit model of inhalation anthrax. Clin Vac Immunol. 2012; 19(8): 1158–1164.
Yee SB, Hatkin JM, Dyer DN, Orr SA, Pitt MLM. Aerosolized Bacillus anthracis infection in New Zealand white rabbits: natural history and intravenous levofloxacin treatment. Comp Med. 2010; 60(6): 461–468.
Foss MH, Weibel DB. Oligochlorophens are potent inhibitors of Bacillus anthracis. Antimicrob Agents Chemother. 2010; 54(9): 3988–3990.
Heine HS, Bassett J, Miller L, Purcell, BK, Byrne WR. Efficacy of daptomycin against Bacillus anthracis in a murine model of anthrax spore inhalation. Antimicrob Agents Chemother. 2010; 54(10):4471–4473.
Ambrose PG, Forrest A, Craig WA, Rubino ChM, Bhavnani SM, Drusano GL, et al. Pharmacokinetics-pharmacodynamics of gatifloxacin in lethal murine Bacillus anthracis inhalation infection model. Antimicrob Agents Chemother. 2007; 51(12): 4351–4355.
Heine HS, Purcell BK, Bassett J, Miller L, Goldstein BP. Activity of dalbavancin against Bacillus anthracis in vitro and in a mouse inhalation anthrax model. Antimicrob Agents Chemother. 2010; 54(3): 991–996.
Wycoff KL, Belle A, Deppe D, Schaefer L, Maclean JM, Haase S, et al. Recombinant anthrax toxin receptor – Fc fusion proteins produced in plants protect rabbits against inhalational anthrax. Antimicrob Agents Chemother. 2011; 55(1): 132–139.
Arzola L, Chen J, Rattanaporn K, Maclean JM, McDonald KA. Transient co-expression of post-transcriptional gene silencing suppressors for increased in Planta expression of a recombinant anthrax receptor fusion protein. Int J Mol Sci. 2011; 12: 4975–4990.
Opal SM, Lim Y-P, Cristofaro P, Artenstein AW, Kessimian N, DelSesto D, et al. Inter-alpha inhibitor proteins: a novel therapeutic strategy for experimental anthrax infection. Shock. 2011; 35(1): 42–44.
Wu G, Feng Ch, Cao S, Guo A, Liu Z. Identification of new dominant – negative mutants of anthrax protective antigen using directed evolution. Appl Biochem Biotechnol. 2012; 168(5): 1302–1310.
Forino M, Johnson S, Wong TY, Rozanov DV, Savinov AY, Li W, et al. Efficient synthetic inhibitors of anthrax lethal factor. PNAS. 2005; 102(27): 9499–9504.
Editor’s Blog at WRAL Tech Wire. FDA approves GlaxoSmithKline drug for treatment of anthrax by Staff, telegram reports. GSK, Biotech&Life Science, 2012.
Migone T-S, Subramanian GM, Zhong J, Healey LM, Corey A, Devalaraja M, et al. Raxibacumab for the treatment of inhalational anthrax. N Engl J Med. 2009; 361(2): 135–144.
Mazumdar S. Raxibacumab. mAbs. 2009; 1(6): 531–538.
Schneemann A, Manchester M. Anti-toxin antibodies in prophylaxis and treatment of inhalation anthrax. Future Microbiol. 2009; 4: 35–43.
Support use of Raxibacumab (Abthrax) for the treatment of inhalation anthrax. (acces: 2013.07.30).
Ramasamy S, Liu CQ, Tran H, Gubala A, Gauci P, McAllister J, et al. Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents. Br J Pharmacol. 2010; 161: 721–748.
Monoclonal antibody for treatment of inhalation anthrax. A service of the U.S. National Institutes of Health. (acces: 2013.07.30).
Welkos S, Little S, Friedlander A, Fritz D, Fellows P. The role of antibodies to Bacillus anrhracis and anthrax toxin components in inhibiting the early stages of infection by anthrax spores. Microbiology 2001; 147: 1677–1685.
Mechaly A, Levy H, Epstein E, Rosenfeld R, Marcus H, Ben-Arie E, et al. A novel mechanism for antibody – based anthrax toxin neutralization: inhibition of prepore – to – pore conversion. J Biol Chem. 2012; 287(39): 32665–32673.
Chen Z, Moayeri M, Purcell R. Monoclonal antibody therapies against anthrax. Toxins. 2011; 3: 1004–1019.
Smith K, Crowe SR, Garman L, Guthridge C, Muther JJ, McKee E, et al. Human monoclonal antibodies generated following vaccination with AVA provide neutralization by blocking furin cleavage but not by preventing oligomerization. Vaccine 2012; 30(28): 4276–4283.
Herrmann JE, Wang S, Zhang Ch, Panchal RG, Bavari S, Lyons CR, et al. Passive immunotherapy of Bacillus anthracis pulmonary infection in mice with antisera produced by DNA immunization. Vaccine 2006; 24: 5872–5880.
Klinman DM, Xie H, Little SF, Currie D, Ivins BE. CpG oligonucleotides improve the protective immune response induced by the anthrax vaccination of rhesus macaques. Vaccine 2004; 22: 2881–2886.
Xie H, Gursel I, Ivins BE, Singh M, O’Hagan DT, Ulmer JB, et al. CpG oligodeoxynucleotides adsorbed onto polylactide–co-glycolide microparticles improve the immunogenicity and protective activity of the licensed anthrax vaccine. Infect Immun. 2005; 73(2): 828–833.
Mirski T, Gryko R, Bartoszcze M, Bielawska-Drózd A, Tyszkiewicz W. Peptydy przeciwdrobnoustrojowe – nowe możliwości zwalczania infekcji u ludzi i zwierząt. Medycyna Wet. 2011; 67(8): 517–521 (in Polish).
Galoyan AA, Grigoryan SL, Badalyan KV. Treatment and prophylaxis of anthrax by new neurosecretory cytokines. Neurochem Res. 2006; 31: 795–803.
Beer M, Liu Ch-Q. Panning of a phage display library against a synthetic capsule for peptide ligands that bind to the native capsule of Bacillus anthracis. PLoS ONE. 2012; 7(9): e45472.
Wade D. CAMELs against anthrax. (acces: 2013.07.30).
Thwaite JE, Hibbs S, Titball RW, Atkins TP. Proteolytic degradation of human antimicrobial peptide LL-37 by Bacillus anthracis may contribute to virulence. Antimicrob Agents Chemother. 2006; 50(7): 2316–2322.
Walberg K, Baron S, Poast J, Schwartz B, Izotova L, Pestka S, Peterson JW. Interferon protects mice against inhalation anthrax. J Interferon Cytokine Res. 2008; 28: 597–602.
Barrow EW, Dreier J, Reinelt S, Bourne PC, Barrow WW. In vitro efficacy of new antifolates against trimethoprim-resistant Bacillus anthracis. Antimicrob Agents Chemother. 2007; 51(12): 4447–4452.
Beierlein JM, Frey KM, Bolstad DB, Pelphrey PM, Joska TM, Smith AE, et al. Synthetic and crystallographic studies of a new inhibitor series targeting Bacillus anthracis dihydrofolate reductase. J Med Chem. 2008; 51(23): 7532–7540.
Yoong P, Schuch R, Nelson D, Fischetti VA. PlyPH, a bacteriolytic enzyme with a broad pH range of activity and lytic action against Bacillus anthracis. J Bacteriol. 2006; 188(7): 2711–2714.