Deletion of the Aspergillus fumigatus gene encoding the Ras-related protein rhbA reduces virulence in a model of invasive pulmonary aspergillosis

John C. Panepinto, Brian G. Oliver, Jarrod Fortwendel, Darcey L.H. Smith, David S. Askew, Judith C. Rhodes

Research output: Contribution to journalArticle

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Abstract

Aspergillus fumigatus is the predominant mold pathogen in patients who lack functional innate immunity. The A. fumigatus rhbA gene was first identified as a transcript that was upregulated when the organism was grown in the presence of mammalian cells. To gain insight into the function of rhbA in the growth and pathogenesis of A. fumigatus, we constructed a strain that lacks a functional rhbA gene. The ΔrhbA mutant showed a significant reduction in virulence compared to the virulence of the wild type in a mouse model of invasive aspergillosis. Complementation of the deletion with the wild-type gene restored full virulence. Although the ΔrhbA mutant grew as well as the wild type on solid medium containing the rich nitrogen source ammonium, the growth of the mutant was impaired on medium containing poor nitrogen sources. Like the Saccharomyces cerevisiae rhbl mutant, the ΔrhbA mutant exhibited increased uptake of arginine. In addition, the ΔrhbA strain underwent asexual development in submerged cultures, even under ammonium-excess conditions. Growth of the mutant with poor nitrogen sources eliminated both the arginine uptake and submerged asexual development phenotypes. The mutant showed enhanced sensitivity to the TOR kinase inhibitor rapamycin. These findings establish the importance of rhbA for A. fumigatus virulence and suggest a role for rhbA in nutrient sensing.

Original languageEnglish (US)
Pages (from-to)2819-2826
Number of pages8
JournalInfection and Immunity
Volume71
Issue number5
DOIs
StatePublished - May 1 2003

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Invasive Pulmonary Aspergillosis
ras Proteins
Aspergillus fumigatus
Virulence
Nitrogen
Ammonium Compounds
Genes
Arginine
Growth
TOR Serine-Threonine Kinases
Aspergillosis
Sirolimus
Innate Immunity
Saccharomyces cerevisiae
Fungi
Phenotype
Food

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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Deletion of the Aspergillus fumigatus gene encoding the Ras-related protein rhbA reduces virulence in a model of invasive pulmonary aspergillosis. / Panepinto, John C.; Oliver, Brian G.; Fortwendel, Jarrod; Smith, Darcey L.H.; Askew, David S.; Rhodes, Judith C.

In: Infection and Immunity, Vol. 71, No. 5, 01.05.2003, p. 2819-2826.

Research output: Contribution to journalArticle

Panepinto, John C. ; Oliver, Brian G. ; Fortwendel, Jarrod ; Smith, Darcey L.H. ; Askew, David S. ; Rhodes, Judith C. / Deletion of the Aspergillus fumigatus gene encoding the Ras-related protein rhbA reduces virulence in a model of invasive pulmonary aspergillosis. In: Infection and Immunity. 2003 ; Vol. 71, No. 5. pp. 2819-2826.
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