TheAspergillus fumigatusStuA Protein Governs the Up-Regulation of a Discrete Transcriptional Program during the Acquisition of Developmental Competence

Abstract

Members of the Asm1p, Phd1p, Sok2p, Efg1p, and StuAp (APSES) family of fungal proteins regulate morphogenesis and virulence in ascomycetes. We cloned the Aspergillus fumigatus APSES gene encoding StuAp and demonstrated that stuA transcription is markedly up-regulated after the acquisition of developmental competence. A. fumigatus ⌬stuA mutants were impaired in their ability to undergo asexual reproduction. Conidiophore morphology was markedly abnormal, and only small numbers of dysmorphic conidia were produced, which exhibited precocious germination. Whole genome transcriptional analysis during the onset of developmental competence was performed and identified a subset of developmentally regulated genes that were stuA dependent, including a cluster of putative secondary metabolite biosynthesis genes, genes encoding proteins implicated in the regulation of morphogenesis, and genes encoding allergens and other antigenic proteins. Additionally, hyphae of the ⌬stuA mutant displayed reduced expression of the catalase gene CAT1 and were hypersusceptible to hydrogen peroxide.

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

“…This mutant also displays abnormal conidiophore morphology as well as precocious conidial germination (532). Transcriptional analyses revealed a number of StuAdependent transcripts, including secondary metabolite biosynthesis genes, and genes encoding proteins involved in morphogenesis (532). The transcription factor BrlA was also suggested to function downstream of PKA signaling in A. fumigatus (589).…”

“…StuA was identified in A. fumigatus, based on homology to the well-characterized C. albicans PKA downstream effector protein Efg1. ⌬stuA mutant strains are impaired in their ability to undergo asexual reproduction and conidiation (532). This mutant also displays abnormal conidiophore morphology as well as precocious conidial germination (532).…”

“…⌬stuA mutant strains are impaired in their ability to undergo asexual reproduction and conidiation (532). This mutant also displays abnormal conidiophore morphology as well as precocious conidial germination (532). Transcriptional analyses revealed a number of StuAdependent transcripts, including secondary metabolite biosynthesis genes, and genes encoding proteins involved in morphogenesis (532).…”

Caracterização funcional do gene codificador de uma proteína com peptídeo sinal, masA, de Aspergillus fumigatus

“…Diversas oportunidades de investigação de vias metabólicas e classes de genes, e de elucidação dos seus principais mecanismos biológicos foram abertas com a disponibilização do genoma de A. fumigatus (Nierman et al, 2005). O conhecimento da composição, da arquitetura e do mecanismo biossintético bem como o perfil da expressão gênica do A. fumigatus são importantes informações para entender a API e assim levar à determinação de novos alvos terapêuticos  Caracterização do gene masA na formação de biofilme na presença de farnesol;…”

“…Todos os resultados da expressão genica relatica apresentaram significância estatística (p<0,05). (Aguirre et al, 1993;Busby et al, 1996;Miller et al,1991;Sheppard et al, 2005 . O apressório é uma estrutura de função adesiva que auxilia o conídio do fungo fito patogênico a se fixar na superfície da planta.…”