Skip to main content

Advertisement

Log in

Chymostatin as a therapeutic agent of aspergillosis in murine model

  • Original Article
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

The purpose of this study was to evaluate the therapeutic effect of chymostatin, as an elastase inhibitor, in mice with invasive aspergillosis. Two Aspergillus fumigatus (A. fumigatus) isolates obtained from animals (bovine mastitis and avian endophthalmitis) along with elastase-producing A. fumigatus ATCC 26933 were inoculated to seven mice groups according to the protocol. The induction of aspergillosis was confirmed by tissue cultures as well as histopathological examination. Chymostatin, as an elastase inhibitor, was used in treating the infected animals at doses of 50, 100, and 200 μM in four different times. There was no mortality in mice group 6 (mice treated with elastase-producing A. fumigatus ATCC 26933 + 200 μM chymostatin). The mortality rate was calculated approximately 50 % in mice infected with elastase-producing A. fumigatus (group 2). The highest colony forming units was observed in the kidney (35.3 %) and the lowest in the liver (5.9 %). Moreover, Aspergillus hyphae were observed in different tissues obtained from died mice in all groups except group 6. The results showed that chymostatin at a dose of 200 μM could be useful as a feasible replacement agent for the treatment of invasive aspergillosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ahamed A, Singh A, Ward OP (2007) Chymostatin can combine with pepstatin to eliminate extracellular protease activity in cultures of Aspergillus niger NRRL-3. J Ind Microbiol Biotechnol 34:165–169

    Article  CAS  PubMed  Google Scholar 

  • Balloy V, Chignard M (2009) The innate immune response to Aspergillus fumigatus. Microb Infect 11:919–927

    Article  CAS  Google Scholar 

  • Blackman MJ (2000) Proteases involved in erythrocyte invasion by the malaria parasite: function and potential as chemotherapeutic target. Curr Drug Targets 1:59–83

    Article  CAS  PubMed  Google Scholar 

  • Blanco JL, Hontecillas R, Bouza E, Blanco I, Pelaez I, Munoz P (2002) Correlation between the elastase activity index and invasiveness of clinical isolates of Aspergillus fumigatus. J Clin Microbiol 40:1811–1813

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Elter T, Sieniawski M, Gossmannb A, Wickenhauser C, Schröder U, Seifert H, Kuchta J, Burhenne J, Riedel K, Fatkenheuer G, Cornely OA (2006) Voriconazole brain tissue levels in rhinocerebral aspergillosis in a successfully treated young woman. Int J Antimicrob Agents 28:262–265

    Article  CAS  PubMed  Google Scholar 

  • Espinel-Ingroff A (2001) In vitro fungicidal activities of voriconazole, itraconazole and amphotericin B against opportunistic moniliaceous and dematiaceous fungi. J Clin Microbiol 39:954–958

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ghannoum MA (2000) Potential role of phospholipases in virulence and fungal pathogenesis. Clin Microbiol Rev 13:122–143

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hasegawa Y, Nikai T, Shibata Y, Komori Y, Homma M, Ogawa K, Sugihara H (1999) The role of virulence factor of elastolytic proteinase from Aspergillus fumigatus. Jpn J Med Mycol 40:85–91

    Article  CAS  Google Scholar 

  • Kothary MH, Chase T, Macmillan JD (1984) Correlation of elastase production by some strains of Aspergillus fumigatus with ability to cause pulmonary invasive aspergillosis in mice. Infect Immun 4:320–325

    Google Scholar 

  • Latge JP (1999) Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 12:310–350

    CAS  PubMed Central  PubMed  Google Scholar 

  • Low CY, Rotstein C (2011) Emerging fungal infections in immunocompromised patients. F1000 Med Rep 3:1–8

    Article  Google Scholar 

  • Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554

    Article  PubMed  Google Scholar 

  • McNeil MM, Nash SL, Hajjeh RA, Phelan MA, Conn LA, Plikaytis BD, Warnock DW (2001) Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 33:641–647

    Article  CAS  PubMed  Google Scholar 

  • Ogawa K, Okumura Y, Nikai T, Tarumi O, Nakagawa T, Saitou Y (2006) Clinical analysis of chronic pulmonary aspergillosis and discovery of an elastase inhibitor. Jpn J Med Mycol 47:171–178

    Article  Google Scholar 

  • Okumura Y, Ogawa K, Nikai T (2004) Elastase and elastase inhibitor from Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. J Med Microbiol 53:351–354

    Article  CAS  PubMed  Google Scholar 

  • Okumura Y, Ogawa K, Uchiya K, Nikai T (2006) Isolation and characterization of a novel elastase inhibitor, AFLEI from Aspergillus flavus. Jpn J Med Mycol 47:219–224

    Article  CAS  Google Scholar 

  • Okumura Y, Ogawa K, Uchiya K, Nikai T (2007) Characterization and primary structure of elastase inhibitor, AFLEI from Aspergillus flavus. Jpn J Med Mycol 48:13–18

    Article  CAS  Google Scholar 

  • Okumura Y, Ogawa K, Uchida K, Komori Y, Nonogaki T, Nikai T (2008) Biological properties of elastase inhibitor, AFLEI from Aspergillus flavus. Jpn J Med Mycol 49:87–93

    Article  CAS  Google Scholar 

  • Polak A (1998) Experimental models in antifungal chemotherapy. Mycoses 4:1–30

    Article  Google Scholar 

  • Reeves EP, Messina CGM, Doyle S, Kavanagh K (2004) Correlation between gliotoxin production and virulence of Aspergillus fumigatus in Galleria mellonella. Mycopathologia 158:73–79

    Article  CAS  PubMed  Google Scholar 

  • Rementeria A, López-Molina N, Ludwig A, Belén Vivanco A, Bikandi J, Pontón J, Garaizar J (2005) Genus and molecules involved in Aspergillus fumigatus virulence. Rev Iberoam Micol 22:1–23

    Article  PubMed  Google Scholar 

  • Rhodes JC, Bode RB, McCuan-Kirsch CM (1988) Elastase production in clinical isolates of Aspergillus. Diagn Microbiol Infect Dis 10:165–170

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues E, Boudard F, Malic M, Bastid JM, Bastide M (1997) Murine macrophage elastionolytic activity induced by Aspergillus fumigatus strains in vitro: evidence at the expression of two macrophage-induced protease genes. Can J Microbiol 43:649–657

    Article  Google Scholar 

  • Schaal R, Kupfahl C, Buchheidt D, Neomaier M, Findeisen P (2007) Systematic identification of substrates for profiling of secreted proteases from Aspergillus fumigatus. J Microbiol Methods 71:93–100

    Article  CAS  PubMed  Google Scholar 

  • Tarrand JJ, Lichterfeld M, Warraich I, Luna M, Han XY, May GS, Kontoyiannis DP (2003) Diagnosis of invasive septate mold infections. A correlation of microbiological culture and histologic or cytologic examination. Am J Clin Pathol 119:854–858

    Article  PubMed  Google Scholar 

  • Tomee JF, Kauffman HF (2000) Putative virulence factors of Aspergillus fumigatus. Clin Exp Allergy 30:476–484

    Article  CAS  PubMed  Google Scholar 

  • Tronchin G, Bouchara JP, Larcher G, Lissitzky J, Chabasse D (1993) Interaction between Aspergillus fumigatus and basement membrane laminin: binding and substrate degradation. Biol Cell 77:201–208

    Article  CAS  PubMed  Google Scholar 

  • Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF (2008) Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 46:327–360

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work was funded by the Vice-Chancellor in research affairs of Tarbiat Modares University and Babol University of Medical Sciences. We thank Dr. SH Mirhendi for his helping to authors (Department of Medical Parasitology and Mycology, Institute of Health research, Tehran University of Medical Sciences).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ali Reza Khosravi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Omran, S.M., Khosravi, A.R., Shokri, H. et al. Chymostatin as a therapeutic agent of aspergillosis in murine model. Comp Clin Pathol 23, 1–5 (2014). https://doi.org/10.1007/s00580-012-1559-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-012-1559-6

Keywords

Navigation