Systematic Global Analysis of Genes Encoding Protein Phosphatases in Aspergillus fumigatus

نویسندگان

  • Lizziane K. Winkelströter
  • Stephen K. Dolan
  • Thaila Fernanda dos Reis
  • Vinícius Leite Pedro Bom
  • Patrícia Alves de Castro
  • Daisuke Hagiwara
  • Raneem Alowni
  • Gary W. Jones
  • Sean Doyle
  • Neil Andrew Brown
  • Gustavo H. Goldman
چکیده

Aspergillus fumigatus is a fungal pathogen that causes several invasive and noninvasive diseases named aspergillosis. This disease is generally regarded as multifactorial, considering that several pathogenicity determinants are present during the establishment of this illness. It is necessary to obtain an increased knowledge of how, and which, A. fumigatus signal transduction pathways are engaged in the regulation of these processes. Protein phosphatases are essential to several signal transduction pathways. We identified 32 phosphatase catalytic subunit-encoding genes in A. fumigatus, of which we were able to construct 24 viable deletion mutants. The role of nine phosphatase mutants in the HOG (high osmolarity glycerol response) pathway was evaluated by measuring phosphorylation of the p38 MAPK (SakA) and expression of osmo-dependent genes. We were also able to identify 11 phosphatases involved in iron assimilation, six that are related to gliotoxin resistance, and three implicated in gliotoxin production. These results present the creation of a fundamental resource for the study of signaling in A. fumigatus and its implications in the regulation of pathogenicity determinants and virulence in this important pathogen.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Phylogenetic analysis of HSP70 gene of Aspergillus fumigatus reveals conservation intra-species and divergence inter-species

Aspergillus fumigatus is a saprophyte fungus, widely spread in a variety of ecologicalniches and the most prevalent aspergilli responsible for human and animal invasiveaspergillosis. The first step to develop novel and efficient therapies is the identificationand understanding of the key tolerance and virulence factors of pathogens. The mainfocus of the present study is to perform the similarit...

متن کامل

The Fumagillin Gene Cluster, an Example of Hundreds of Genes under veA Control in Aspergillus fumigatus

Aspergillus fumigatus is the causative agent of invasive aspergillosis, leading to infection-related mortality in immunocompromised patients. We previously showed that the conserved and unique-to-fungi veA gene affects different cell processes such as morphological development, gliotoxin biosynthesis and protease activity, suggesting a global regulatory effect on the genome of this medically re...

متن کامل

Characterization of essential genes by parasexual genetics in the human fungal pathogen Aspergillus fumigatus: impact of genomic rearrangements associated with electroporation of DNA.

We have evaluated the usefulness of parasexual genetics in the identification of genes essential for the growth of the human fungal pathogen Aspergillus fumigatus. First, essentiality of the A. fumigatus AfFKS1 gene, encoding the catalytic subunit of the beta-(1,3)-glucan synthase complex, was assessed by inactivating one allele of AfFKS1 in a diploid strain of A. fumigatus obtained using adequ...

متن کامل

The ergosterol biosynthesis pathway, transporter genes, and azole resistance in Aspergillus fumigatus.

The continuous use of triazoles can result in the development of drug resistance. Azole-resistant clinical isolates, spontaneous and induced mutants of Aspergillus fumigatus have been documented. The azoles block the ergosterol biosynthesis pathway by inhibiting the enzyme 14-alpha-demethylase, product of the CYP51. Fungal azole resistance involves both amino acid changes in the target site tha...

متن کامل

Contributions of Aspergillus fumigatus ATP-binding cassette transporter proteins to drug resistance and virulence.

In yeast cells such as those of Saccharomyces cerevisiae, expression of ATP-binding cassette (ABC) transporter proteins has been found to be increased and correlates with a concomitant elevation in azole drug resistance. In this study, we investigated the roles of two Aspergillus fumigatus proteins that share high sequence similarity with S. cerevisiae Pdr5, an ABC transporter protein that is c...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2015