TARGET-SPECIFIC SCREENING OF ANTIVIRULENCE PREPARATIONS FOR CHRONIC INFECTION THERAPY


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Abstract

Global spread of clinically significant strains resistant to antibiotics necessitated the development of new approaches to generation of antibacterial preparations. Selection of virulence factors as targets for new preparations is an alternative approach to therapy of infections caused by resistant strains and chronic infectious diseases. Contemporary state of research aimed at target selection among virulence factors of pathogenic for humans bacteria that cause chronic infections, and screening of specific inhibitors of these targets are examined. Analysis of limited data of therapeutic activity of selected preparations, i.e. experimental confirmation of the proposed concept, is provided.

About the authors

N. A Zigangirova

Gamaleya Research Institute of Epidemiology and Microbiology, Moscow, Russia

A. L Gintsburg

Gamaleya Research Institute of Epidemiology and Microbiology, Moscow, Russia

References

  1. Зигангирова Н.А., Зорина В.В., Гинцбург А.Л. Система секреции III типа у бактерий - перспективная мишень для разработки нового поколения антибактериальных препаратов. Вестн. РАМН. 2008, 10: 34-39.
  2. Сидоренко С.В. Инфекционый процесс как «диалог» между хозяином и паразитом. Клинич. микробиол. антимикроб. химиотерап. 2001, 3 (4): 301-315.
  3. Супотницкий М.В. Микроорганизмы, токсины и эпидемии. Озон, 2000.
  4. Autret N., Charbit A. Lessons from signaturetagged mutagenesis on the infectious mechanisms of pathogenic bacteria. FEMS Microbiol. Rev. 2005, 29: 703-717.
  5. Baron C., Coombes B. Targeting bacterial secretion systems: benefits of disarmament in the microcosm. Infect. Dis. Drug Targ. 2007, 7 (1):19-27.
  6. Bjarnsholt T., Givskov M. Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens. Philos Trans R. Soc. Lond. B. Biol. Sci. 2007, 362 (1483): 1213-1222.
  7. Cegelski L., Marshall G., Eldridge G. et al. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 2008, 6 (1): 17-27.
  8. Clatworthy A.E., Pierson E., Hung D.T. Targeting virulence: a new paradigm for antimicrobial therapy. Nat. Chem. Biol. 2007, 3 (9): 541-548.
  9. Coates A.R.M., Hu Y. Novel approaches to developing new antibiotics for bacterial infections. Br. J. Pharmacol. 2007, 152 (8): 1147-1154.
  10. Coburn B., Sekirov I., Finlay B.B. Type III secretion systems and disease. Clin. Microbiol. Rev. 2007, 20 (4): 535-549.
  11. Dahlgren M.K., Kauppi A.M., Olsson I. et al. Design, synthesis, and multivariate quantitative structure-activity relationship of salicylanilidespotent inhibitors of type III secretion in Yersinia. J. Med. Chem. 2007, 50 (24): 6177-6188.
  12. Ekins S., Mestres J., Testa B. In silico pharmacology for drug discovery: applications to targets and beyond. Br. J. Pharmacol. 2007, 152 (1): 21-37.
  13. Gauthier A., Robertson M.L., Lowden M. et al. Transcriptional inhibitor of virulence factors in enteropathogenic Escherichia coli. Antimicrob. Agents Chemother. 2005, 49 (10): 4101-4109.
  14. Hefty P.S., Stephens R. Chlamydial type III secretion system is encoded on ten operons preceded by sigma 70-like promoter elements. J.Bacteriol. 2007, 189 (1): 198-206.
  15. Hentzer M. et al. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J. 2003, 22: 3803-3815.
  16. Hudson D., Layton A.N., Field T. et al. Inhibition of type III secretion in Salmonella enterica serovar Typhimurium by small-molecule inhibitors. Antimicrob. Agents Chemother. 2007, 51 (7): 2631-2635.
  17. Hueck C. Type III secretion systems in bacterial pathogens of animals and plants. Microbiol.Mol. Biol.Rev. 1998, 62 (2): 379-433.
  18. Kauppi A.M., Nordfelth R., Uvell H. et al. Targeting bacterial virulence: Inhibitors of type III secretion in Yersinia. Chemistry Biology. 2003, 10 (3): 241-249.
  19. Kihlberg J., Magnusson G. Use of carbohydrates and peptides in studies of adhesion of patho- genic bacteria and in efforts to generate carbohydrate-specific T cells. Pure Appl. Chem. 1996, 68: 2119-2128.
  20. Larsson A. et al. Multivariate design, synthesis, and biological evaluation of peptide inhibitors of FimC/FimH protein-protein interactions in uropathogenic Escherichia coli. J. Med. Chem. 2005, 48: 935-945.
  21. Lee Y.M., Almqvist F., Hultgren S.J. Targeting virulence for antimicrobial chemotherapy. Curr. Opin. Pharmacol. 2003, 3: 513-519.
  22. Mahan M.J., Slauch J.M., Mekalanos J.J. Selection of bacterial virulence genes that are specifically induced in host tissues. Science. 1993, 259: 686-688.
  23. Marra A. Targeting virulence for antibacterial chemotherapy: identifying and characterising virulence factors for lead discovery. Drugs R. D. 2006, 7 (1): 1-16.
  24. Muschiol S., Bailey L., Gylfe A. et al. A smallmolecule inhibitor of type III secretion inhibits different stages of the infectious cycle of Chlamydia trachomatis. PNAS. 2006, 103 (39): 14566-14571.
  25. Nordfelth R., Kauppi A.M., Norberg H.A. et al. Small-molecule inhibitors specifically targeting type III secretion. Infect. Immun. 2005, 73 (5): 3104-3114.
  26. Opperman T., Ling L., Moir D.T. Microbial pathogen genomes - new strategies for identify- ing therapeutic and vaccine targets. Expert Opin. Ther. Targets. 2003, 7 (4): 469-473.
  27. Saye D.E. Recurring and antimicrobial-resistant infections: considering the potential role of bio- films in clinical practice. Ostomy Wound Manage. 2007, 53: 46-62.
  28. Snyder J.A. et al. Transcriptome of uropathogenic E.coli during urinary tract infection. Infect. Immun. 2004, 72 (11): 6373-6381.
  29. Svensson A. et al. Design and evaluation of pilicides: potential novel antibacterial agents directed against uropathogenic Escherichia coli. Chembiochem. 2001, 2: 915-918.
  30. Telford J.L., Barocchi Mle A., Margarit I. et al. Pili in Gram-positive pathogens. Nature Rev. Microbiol. 2006, 4: 509-519.
  31. Veenendaal A.K., Sundin C., Blocker A.J. Smallmolecule type III secretion system inhibitors block assembly of the Shigella type III secretion. J. Bacteriol. 2009, 191 (2): 563-570.
  32. Zarivach R. et al. Structural analysis of a prototypical ATPase from the type III secretion system. Nat. Struct. Mol. Biol. 2007, 14: 131-137.

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