State and prospects of development of means of prevention and treatment of poisoning by biological toxins – potential agents of bioterrorism

Abstract

Toxins of biological origin are regulatory elements that act in heterologous cell systems beyond their control and shift the balance of physiological processes occurring in them. In nature, biological toxins are divided into phytotoxins, zootoxins, microbial toxins, synthetic toxins, for her role in the life of the organism-producer – endotoxins and exotoxins (acetoxy), and the effect on target organism – neurotoxins, cytotoxins (toxin effectors), toxins, enzymes, toxins, enzyme inhibitors. A wide variety of biotoxins and their sufficiently high biological activity in relation to the living organism, as well as the lack of most effective specific means of prevention and treatment of pathological processes caused by them, raises the problem of their search and development in the category of significant and urgent problems of modern health care and military medicine. With regard to the latter, the significance and relevance of the problem are confirmed by the high probability of using biotoxins as potential agents of bioterrorism. Close attention is paid to the current state of prevention and treatment of poisoning by biotoxins, analysis of information concerning the prospects of use for these purposes of antibody drugs. The first results on the preventive and therapeutic efficacy of polyvalent heterologous sera in staphylococcal enterotoxin, murine-human chimeric antibodies against staphylococcal enterotoxin B. in preclinical conditions, drugs based on monoclonal antibodies to cholera toxin and Shiga toxin were obtained.

Keywords

agents of bioterrorism / antibody preparations biotoxins / bioterrorism / botulinum neurotoxins / treatment of intoxication with biotoxins / prevention of intoxication with biotoxins / ricin / Shiga toxin

References

[1] Магазов, Р.Ш. Вакцинопрофилактика клостридиальных инфекций / Р.Ш. Магазова [и др.]. – Уфа: Гилем, Башк. энцикл., 2016. – 288 с.

[2] Barr, J.R. Botulinum neurotoxin detection and differentiation by mass spectrometry/ J.R. Barr [et al.] // Emerg. Infect. Dis. – 2005. – Vol. 11, № 10. – P.1578–1583.

[3] Berger, T. Toxins as biological weapons for terror–characteristics, challenges and medical countermeasures: a mini review / T. Berger [et al.] // Disaster Mil. Med. – 2016. – Vol. 2. – P. 7–15.

[4] Busl, K.M. Treatment of neuroterrorism / К.M. Busl, T.B. Bleck // Neurotherapeutics. – 2012. – Vol. 9, № 1. – P. 139–157.

[5] Centers for Disease Control and Prevention (CDC) Notice of CDC’s discontinuation of investigational pentavalent (ABCDE) botulinum toxoid vaccine for workers at risk for occupational exposure to botulinum toxins // MMWR Morb. Mortal. Wkly Rep. – 2011. – Vol. 60. – P. 1454–1455.

[6] Clarke, S.C. Bacteria as potential tools in bioterrorism, with an emphasis on bacterial toxins / S.C. Clarke // Br. J. Biomed Sci. – 2005. – Vol. 62, № 1. – P. 40–46.

[7] Darling, R.G. Medical management of biological casualties handbook / R.G. Darling, J.B. Woods // Fort Detrick, MD: US Army Medical Research Institute of Infectious Diseases, 2004. – P. 80–91.

[8] Jacobs, M.K. The history of biologic warfare and bioterrorism / M.K. Jacobs // Dermatol. Clin. – 2004. – Vol. 22, № 3. – P. 231–246.

[9] Khardori, N. Bioterrorism and bioterrorism preparedness: historical perspective and overview / N. Khardori // Infect. Dis. Clin. North. Am. – 2006. – Vol. 20. – P. 179–211.

[10] Madsen, J.M. Toxins as weapons of mass destruction. A comparison and contrast with biological–warfare and chemical- warfare agents / J.M. Madsen // Clin. Lab. Med. – 2001. – Vol. 21. – P. 593–605.

[11] Marks, J.D. Medical aspects of biologic toxins / J.D. Marks // Anesthesiol. Clin. North. Am. – 2004. – Vol. 22. – P. 509–532.

[12] Moran-Gilad. J. Ricin and abrin as potential bioterror agents [Hebrew] / J. Moran-Gilab // J Isr. Millitry Med. – 2010. – Vol. 7. – P. 124–126.

[13] O’Hara, J.M. Comparative efficacy of two leading candidate ricin toxin a subunit vaccines in mice / J.M. O’Hara [et al.] // Clin. Vaccine Immunol. – 2013. – Vol. 20. – P. 789–794.

[14] Paddle, B.M. Therapy and prophylaxis of inhaled biological toxins / B.M. Paddle // J Appl. Toxicol. – 2013. – Vol. 33, № 3. – P. 139–170.

[15] Pinchuk, I.V. Staphylococcal enterotoxins / I.V. Pinchuk [et al.] // Toxins. – 2010. – Vol. 2. – P. 2177–2197.

[16] Pita, R. Toxins as Weapons: A Historical Review / R. Pita [et al.] // Forensic Sci. Rev. – 2014. – Vol. 26, № 2. – P. 85–96.

[17] Popoff, M.R. Epsilon toxin: a fascinating pore-forming toxin / M.R. Popoff // FEBS J. – 2011. – Vol. 278. – P. 4602–4615.

[18] Riedel, S. Biological warfare and bioterrorism: a historical review / S. Riedel // Proc. (Bayl. Univ. Med Cent). – 2004. – Vol. 17, № 4. – P. 400–406.

[19] Robertson, S.L. Evidence for a prepore stage in the action of Clostridium perfringens epsilon toxin / S.L. Robertson [et al.] // PLoS One. – 2011. – Vol. 6. – P. e22053.

[20] Rosen, O. Improved detection of botulinum type E by rational design of a new peptide substrate for endopeptidase-mass spectrometry assay / O. Rosen [et al.] // Anal. Biochem. – 2014. – Vol. 456. – P. 50–52.

[21] Rosen, O. A new peptide substrate for enhanced BoNT/B detection by endopep-LC-MS-MS/MRM assay / O. Rosen [et al.] // Anal. Biochem. – 2015. – Vol. 473. – P. 7–10.

[22] Stirpe, F. Ribosome-inactivating proteins: from toxins to useful proteins / F. Stirpe // Toxicon. – 2013. – Vol. 67. – P.12–16.

[23] Vale, A. Bacterial Toxins as Pathogen Weapons Against Phagocytes / A. Vale, D. Cabanes, S. Sousa // Front Microbiol. – 2016. – Vol. 7. – P. 42–54.

[24] Vatansever, F. Can biowarfare agents be defeated with light? / F. Vatansever [et al.] // Virulence. – 2013. – Vol. 4, № 8. – P. 796–825.

[25] Villar, R. Botulism: the many faces of botulinum toxin and its potential for bioterrorism / R. Villar, S. Elliott, K. Davenport // Infect. Dis. Clin. North Am. – 2006. – Vol. 20. – P. 313–327.

[26] Yan, X. Structural and functional analysis of the pore-forming toxin NetB from Clostridium perfringens / X. Yan [et al.] // mBio – 2013. – Vol. 4, № 1. – P. e0009–e00019.

RIGHTS & PERMISSIONS

Stepanov A.V., Ivchenko E.V., Dergachev V.B.