Limits...
Transcription Factor SomA Is Required for Adhesion, Development and Virulence of the Human Pathogen Aspergillus fumigatus.

Lin CJ, Sasse C, Gerke J, Valerius O, Irmer H, Frauendorf H, Heinekamp T, Straßburger M, Tran VT, Herzog B, Braus-Stromeyer SA, Braus GH - PLoS Pathog. (2015)

Bottom Line: Loss of the somA gene in A. fumigatus resulted in a slow growth phenotype and a block in asexual development.A adherence assay with the conditional somA expression strain indicated that SomA is required for biofilm formation.Infection assays with fertilized chicken eggs as well as with mice revealed that SomA is required for pathogenicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Microbiology and Genetics, Institute of Microbiology & Genetics, Georg-August-University Göttingen, Göttingen, Germany.

ABSTRACT
The transcription factor Flo8/Som1 controls filamentous growth in Saccharomyces cerevisiae and virulence in the plant pathogen Magnaporthe oryzae. Flo8/Som1 includes a characteristic N-terminal LUG/LUH-Flo8-single-stranded DNA binding (LUFS) domain and is activated by the cAMP dependent protein kinase A signaling pathway. Heterologous SomA from Aspergillus fumigatus rescued in yeast flo8 mutant strains several phenotypes including adhesion or flocculation in haploids and pseudohyphal growth in diploids, respectively. A. fumigatus SomA acts similarly to yeast Flo8 on the promoter of FLO11 fused with reporter gene (LacZ) in S. cerevisiae. FLO11 expression in yeast requires an activator complex including Flo8 and Mfg1. Furthermore, SomA physically interacts with PtaB, which is related to yeast Mfg1. Loss of the somA gene in A. fumigatus resulted in a slow growth phenotype and a block in asexual development. Only aerial hyphae without further differentiation could be formed. The deletion phenotype was verified by a conditional expression of somA using the inducible Tet-on system. A adherence assay with the conditional somA expression strain indicated that SomA is required for biofilm formation. A ptaB deletion strain showed a similar phenotype supporting that the SomA/PtaB complex controls A. fumigatus biofilm formation. Transcriptional analysis showed that SomA regulates expression of genes for several transcription factors which control conidiation or adhesion of A. fumigatus. Infection assays with fertilized chicken eggs as well as with mice revealed that SomA is required for pathogenicity. These data corroborate a complex control function of SomA acting as a central factor of the transcriptional network, which connects adhesion, spore formation and virulence in the opportunistic human pathogen A. fumigatus.

No MeSH data available.


Related in: MedlinePlus

SomA is required for virulence in an egg and a mouse model of invasive aspergillosis.(A) Survival rate of eggs inoculated with the indicated strains. Addition of doxycycline was not performed in the somA complemented mutant and Tet-somA Off state. (B) Survival rate of mice infected with the indicated strains. (C) Histological pictures of mouse lungs obtained from indicated dates after infection with the corresponding strains or PBS.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4631450&req=5

ppat.1005205.g008: SomA is required for virulence in an egg and a mouse model of invasive aspergillosis.(A) Survival rate of eggs inoculated with the indicated strains. Addition of doxycycline was not performed in the somA complemented mutant and Tet-somA Off state. (B) Survival rate of mice infected with the indicated strains. (C) Histological pictures of mouse lungs obtained from indicated dates after infection with the corresponding strains or PBS.

Mentions: In an egg infection model, the ΔsomA mutant was not included due to the severely impaired conidiation. The eggs infected with the inactive Tet-somA strain without doxycycline (Off) had no significant difference in mortality of infected eggs compared to the PBS control (p = 0.58; log-rank test). The Tet-somA (Off) showed attenuated virulence compared to the ΔakuA strain, the somA complemented and the Tet-somA (On) (p<0.05). In contrast, the On state of the Tet-somA strain which was induced by doxycycline showed similar virulence to the ΔakuA strain or the somA complemented strain (Fig 8A).


Transcription Factor SomA Is Required for Adhesion, Development and Virulence of the Human Pathogen Aspergillus fumigatus.

Lin CJ, Sasse C, Gerke J, Valerius O, Irmer H, Frauendorf H, Heinekamp T, Straßburger M, Tran VT, Herzog B, Braus-Stromeyer SA, Braus GH - PLoS Pathog. (2015)

SomA is required for virulence in an egg and a mouse model of invasive aspergillosis.(A) Survival rate of eggs inoculated with the indicated strains. Addition of doxycycline was not performed in the somA complemented mutant and Tet-somA Off state. (B) Survival rate of mice infected with the indicated strains. (C) Histological pictures of mouse lungs obtained from indicated dates after infection with the corresponding strains or PBS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631450&req=5

ppat.1005205.g008: SomA is required for virulence in an egg and a mouse model of invasive aspergillosis.(A) Survival rate of eggs inoculated with the indicated strains. Addition of doxycycline was not performed in the somA complemented mutant and Tet-somA Off state. (B) Survival rate of mice infected with the indicated strains. (C) Histological pictures of mouse lungs obtained from indicated dates after infection with the corresponding strains or PBS.
Mentions: In an egg infection model, the ΔsomA mutant was not included due to the severely impaired conidiation. The eggs infected with the inactive Tet-somA strain without doxycycline (Off) had no significant difference in mortality of infected eggs compared to the PBS control (p = 0.58; log-rank test). The Tet-somA (Off) showed attenuated virulence compared to the ΔakuA strain, the somA complemented and the Tet-somA (On) (p<0.05). In contrast, the On state of the Tet-somA strain which was induced by doxycycline showed similar virulence to the ΔakuA strain or the somA complemented strain (Fig 8A).

Bottom Line: Loss of the somA gene in A. fumigatus resulted in a slow growth phenotype and a block in asexual development.A adherence assay with the conditional somA expression strain indicated that SomA is required for biofilm formation.Infection assays with fertilized chicken eggs as well as with mice revealed that SomA is required for pathogenicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Microbiology and Genetics, Institute of Microbiology & Genetics, Georg-August-University Göttingen, Göttingen, Germany.

ABSTRACT
The transcription factor Flo8/Som1 controls filamentous growth in Saccharomyces cerevisiae and virulence in the plant pathogen Magnaporthe oryzae. Flo8/Som1 includes a characteristic N-terminal LUG/LUH-Flo8-single-stranded DNA binding (LUFS) domain and is activated by the cAMP dependent protein kinase A signaling pathway. Heterologous SomA from Aspergillus fumigatus rescued in yeast flo8 mutant strains several phenotypes including adhesion or flocculation in haploids and pseudohyphal growth in diploids, respectively. A. fumigatus SomA acts similarly to yeast Flo8 on the promoter of FLO11 fused with reporter gene (LacZ) in S. cerevisiae. FLO11 expression in yeast requires an activator complex including Flo8 and Mfg1. Furthermore, SomA physically interacts with PtaB, which is related to yeast Mfg1. Loss of the somA gene in A. fumigatus resulted in a slow growth phenotype and a block in asexual development. Only aerial hyphae without further differentiation could be formed. The deletion phenotype was verified by a conditional expression of somA using the inducible Tet-on system. A adherence assay with the conditional somA expression strain indicated that SomA is required for biofilm formation. A ptaB deletion strain showed a similar phenotype supporting that the SomA/PtaB complex controls A. fumigatus biofilm formation. Transcriptional analysis showed that SomA regulates expression of genes for several transcription factors which control conidiation or adhesion of A. fumigatus. Infection assays with fertilized chicken eggs as well as with mice revealed that SomA is required for pathogenicity. These data corroborate a complex control function of SomA acting as a central factor of the transcriptional network, which connects adhesion, spore formation and virulence in the opportunistic human pathogen A. fumigatus.

No MeSH data available.


Related in: MedlinePlus