Genetic Interactions Between Aspergillus fumigatus Basic Leucine Zipper (bZIP) Transcription Factors AtfA, AtfB,

Lilian Pereira Silva1, Maria Augusta Crivelente Horta1, Gustavo Henrique Goldman1

  • 1Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.

Frontiers in Fungal Biology
|September 25, 2023
PubMed

Insights

Investigating Aspergillus fumigatus transcription factors AtfA-D reveals complex genetic and physical interactions. These interactions influence fungal virulence and stress responses, impacting trehalose and glycogen accumulation.

Area of Science:

  • Mycology
  • Molecular Biology
  • Fungal Pathogenesis

Background:

  • Aspergillus fumigatus is an opportunistic fungal pathogen causing invasive aspergillosis in immunocompromised individuals.
  • Transcription factors (TFs) play crucial roles in fungal adaptation and virulence.
  • Previous studies have initiated the characterization of AtfA-D TFs in A. fumigatus.

Purpose of the Study:

  • To investigate the genetic and physical interactions among Aspergillus fumigatus transcription factors AtfA-D.
  • To determine the role of AtfA-D interactions in fungal response to stress conditions.
  • To assess the impact of AtfA-D interactions on A. fumigatus virulence and TF localization.

Main Methods:

  • Construction and analysis of double null mutants for all combinations of ΔatfA, ΔatfB, ΔatfC, and ΔatfD.
  • Assessment of fungal susceptibility to various stressing conditions (e.g., sorbitol, H2O2).
  • Subcellular localization studies using fluorescently tagged TFs (AtfA:GFP, AtfB:GFP, etc.) under normal and stress conditions.
  • Co-immunoprecipitation assays to identify physical interactions between AtfA-D TFs and the MAPK SakA.

Main Results:

  • Complex genetic interactions among AtfA-D TFs were identified, affecting stress response.
  • AtfA-D TF interactions were shown to influence A. fumigatus virulence in Galleria mellonella.
  • AtfA:GFP predominantly localized to the nucleus, while AtfB, -C, and -D:GFP showed dynamic nuclear translocation (20-80%) under stress.
  • All possible heterodimers of AtfA-D were found to interact physically.
  • AtfA-D TFs physically interact with MAPK SakA under normal and stress conditions.
  • These TFs are involved in trehalose and glycogen accumulation and carbon source metabolism.

Conclusions:

  • The AtfA-D transcription factors exhibit intricate genetic and physical interactions crucial for Aspergillus fumigatus stress adaptation and virulence.
  • Nuclear localization of AtfB, -C, and -D is regulated by stress, highlighting their dynamic roles.
  • Interactions with MAPK SakA suggest a role in stress signaling pathways.
  • These TFs collectively regulate key metabolic processes, including carbohydrate storage and utilization.

Related Concept Videos

General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.3K
Combinatorial Gene Control02:33

Combinatorial Gene Control

Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.4K
Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
76.0K
Prokaryotic Transcriptional Activators and Repressors01:58

Prokaryotic Transcriptional Activators and Repressors

The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
21.1K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
11.1K