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Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production.

Publication ,  Journal Article
Cramer, RA; Gamcsik, MP; Brooking, RM; Najvar, LK; Kirkpatrick, WR; Patterson, TF; Balibar, CJ; Graybill, JR; Perfect, JR; Abraham, SN; Steinbach, WJ
Published in: Eukaryot Cell
June 2006

The fungal secondary metabolite gliotoxin produced by Aspergillus fumigatus has been hypothesized to be important in the development of invasive aspergillosis. In this study, we addressed this hypothesis by disrupting a nonribosomal peptide synthetase (NRPS) (encoded by gliP) predicted to be involved in gliotoxin production. Mutants with a disrupted gliP locus failed to produce gliotoxin, which confirmed the role of the NRPS encoded by gliP in gliotoxin biosynthesis. We found no morphological, developmental, or physiological defects in DeltagliP mutant strains. In addition, disruption of gliP resulted in down regulation of gene expression in the gliotoxin biosynthesis gene cluster, which was restored with addition of exogenous gliotoxin. This interesting result suggests a role for gliotoxin in regulating its own production. Culture filtrates from the DeltagliP mutant were unable to inhibit ionomycin-dependent degranulation of mast cells, suggesting a role for gliotoxin in suppressing mast cell degranulation and possibly in disease development. However, the DeltagliP mutant did not have an impact on survival or tissue burden in a murine inhalational model of invasive aspergillosis. This result suggests that gliotoxin is not required for virulence in an immunosuppressed host with an invasive pulmonary infection.

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Published In

Eukaryot Cell

DOI

ISSN

1535-9778

Publication Date

June 2006

Volume

5

Issue

6

Start / End Page

972 / 980

Location

United States

Related Subject Headings

  • Virulence Factors
  • Rats
  • Phenotype
  • Peptide Synthases
  • Neutropenia
  • Mutation
  • Multigene Family
  • Microbiology
  • Mice
  • Mast Cells
 

Citation

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Cramer, R. A., Gamcsik, M. P., Brooking, R. M., Najvar, L. K., Kirkpatrick, W. R., Patterson, T. F., … Steinbach, W. J. (2006). Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production. Eukaryot Cell, 5(6), 972–980. https://doi.org/10.1128/EC.00049-06
Cramer, Robert A., Michael P. Gamcsik, Rhea M. Brooking, Laura K. Najvar, William R. Kirkpatrick, Thomas F. Patterson, Carl J. Balibar, et al. “Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production.Eukaryot Cell 5, no. 6 (June 2006): 972–80. https://doi.org/10.1128/EC.00049-06.
Cramer RA, Gamcsik MP, Brooking RM, Najvar LK, Kirkpatrick WR, Patterson TF, et al. Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production. Eukaryot Cell. 2006 Jun;5(6):972–80.
Cramer, Robert A., et al. “Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production.Eukaryot Cell, vol. 5, no. 6, June 2006, pp. 972–80. Pubmed, doi:10.1128/EC.00049-06.
Cramer RA, Gamcsik MP, Brooking RM, Najvar LK, Kirkpatrick WR, Patterson TF, Balibar CJ, Graybill JR, Perfect JR, Abraham SN, Steinbach WJ. Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production. Eukaryot Cell. 2006 Jun;5(6):972–980.

Published In

Eukaryot Cell

DOI

ISSN

1535-9778

Publication Date

June 2006

Volume

5

Issue

6

Start / End Page

972 / 980

Location

United States

Related Subject Headings

  • Virulence Factors
  • Rats
  • Phenotype
  • Peptide Synthases
  • Neutropenia
  • Mutation
  • Multigene Family
  • Microbiology
  • Mice
  • Mast Cells