Display options
Cite
Holden DW, Tang CM, Smith JM. Molecular genetics of Aspergillus pathogenicity. Antonie Van Leeuwenhoek. 1994;65(3):251-5doi: 10.1007/BF00871953.
Holden, D. W., Tang, C. M., & Smith, J. M. (1994). Molecular genetics of Aspergillus pathogenicity. Antonie van Leeuwenhoek, 65(3), 251-5. https://doi.org/10.1007/BF00871953
Holden, D W, et al. "Molecular genetics of Aspergillus pathogenicity." Antonie van Leeuwenhoek vol. 65,3 (1994): 251-5. doi: https://doi.org/10.1007/BF00871953
Holden DW, Tang CM, Smith JM. Molecular genetics of Aspergillus pathogenicity. Antonie Van Leeuwenhoek. 1994;65(3):251-5. doi: 10.1007/BF00871953. PMID: 7847892.
Copy Download .nbib Format: NLM
Share it on

Antonie Van Leeuwenhoek. 1994;65(3):251-5. doi: 10.1007/BF00871953.

Molecular genetics of Aspergillus pathogenicity.

Antonie van Leeuwenhoek

D W Holden, C M Tang, J M Smith

Affiliations

  1. Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.

PMID: 7847892 DOI: 10.1007/BF00871953

Abstract

Aspergillus fumigatus is the most frequent cause of Invasive Pulmonary Aspergillosis (IPA), a life-threatening disease of immunosuppressed patients. In addition to a number of general physiological attributes of this fungus, it has been suggested that extracellular elastase and toxins might facilitate its growth in lung tissue. We have investigated the roles of two extracellular proteins, an alkaline protease with elastase activity (AFAlp), and the ribotoxin restrictocin in murine models of IPA. Gene disruption was used to create stable null mutant strains of the fungus lacking one or other protein, and their virulence and histopathological features were compared with an isogenic parental strain in steroid-treated and neutropenic mice. We have been unable to demonstrate any significant differences between the three strains, which shows that, considered independently, these proteins are not important virulence determinants. We are also interested in identifying fungal-specific gene products involved in general metabolism and which are required for growth in the lung, because these could represent new targets for antifungal drugs. For this work a model of murine IPA involving Aspergillus nidulans was established, to take advantage of the many well characterised mutations affecting metabolic pathways. Pathogenicity tests with strains carrying one of two auxotrophic mutations, lysA2 and pabaA1, have shown while lysine biosynthesis is not essential for the fungus to cause pulmonary disease, biosynthesis of p-aminobenzoic acid is essential. We are now in the process of cloning the A. fumigatus pabaA homologue to determine its function and whether this gene is required for growth of the clinically important species in the lung.

References

  1. Antibiot Chemother (1971). 1987;39:136-48 - PubMed
  2. J Med Microbiol. 1991 Jul;35(1):23-8 - PubMed
  3. Infect Immun. 1976 Feb;13(2):527-32 - PubMed
  4. Diagn Microbiol Infect Dis. 1988 Jul;10(3):165-70 - PubMed
  5. Infect Immun. 1993 Jun;61(6):2357-68 - PubMed
  6. Mol Microbiol. 1993 Sep;9(5):1071-7 - PubMed
  7. Infect Immun. 1993 Oct;61(10):4099-104 - PubMed
  8. FEMS Microbiol Lett. 1992 Apr 15;71(2):163-8 - PubMed
  9. FEMS Immunol Med Microbiol. 1993 Jun;7(1):81-91 - PubMed
  10. Clin Allergy. 1976 May;6(3):209-17 - PubMed
  11. Mol Microbiol. 1991 Jul;5(7):1811-5 - PubMed
  12. J Biol Chem. 1991 Jul 15;266(20):12971-5 - PubMed
  13. J Med Microbiol. 1990 Dec;33(4):243-51 - PubMed
  14. FEMS Microbiol Lett. 1993 Jul 15;111(1):31-6 - PubMed
  15. FEMS Microbiol Lett. 1993 Jan 1;106(1):39-46 - PubMed
  16. Infect Immun. 1993 May;61(5):1650-6 - PubMed
  17. Mol Microbiol. 1992 Jun;6(12):1663-71 - PubMed
  18. Endeavour. 1992;16(1):14-6 - PubMed
  19. Nucleic Acids Res. 1991 Mar 11;19(5):1001-6 - PubMed
  20. Infect Immun. 1992 Mar;60(3):728-34 - PubMed
  21. J Bacteriol. 1992 Nov;174(22):7379-84 - PubMed
  22. Infect Immun. 1984 Jan;43(1):320-5 - PubMed

Substances

MeSH terms

Publication Types