Regulatory networks controlling nitrogen sensing and uptake in Candida albicans

PLoS One. 2014 Mar 20;9(3):e92734. doi: 10.1371/journal.pone.0092734. eCollection 2014.

Abstract

Nitrogen is one of the key nutrients for microbial growth. During infection, pathogenic fungi like C. albicans need to acquire nitrogen from a broad range of different and changing sources inside the host. Detecting the available nitrogen sources and adjusting the expression of genes for their uptake and degradation is therefore crucial for survival and growth as well as for establishing an infection. Here, we analyzed the transcriptional response of C. albicans to nitrogen starvation and feeding with the infection-relevant nitrogen sources arginine and bovine serum albumin (BSA), representing amino acids and proteins, respectively. The response to nitrogen starvation was marked by an immediate repression of protein synthesis and an up-regulation of general amino acid permeases, as well as an up-regulation of autophagal processes in its later stages. Feeding with arginine led to a fast reduction in expression of general permeases for amino acids and to resumption of protein synthesis. The response to BSA feeding was generally slower, and was additionally characterized by an up-regulation of oligopeptide transporter genes. From time-series data, we inferred network interaction models for genes relevant in nitrogen detection and uptake. Each individual network was found to be largely specific for the experimental condition (starvation or feeding with arginine or BSA). In addition, we detected several novel connections between regulator and effector genes, with putative roles in nitrogen uptake. We conclude that C. albicans adopts a particular nitrogen response network, defined by sets of specific gene-gene connections for each environmental condition. All together, they form a grid of possible gene regulatory networks, increasing the transcriptional flexibility of C. albicans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological
  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism
  • Amino Acids / metabolism
  • Biological Transport
  • Candida albicans / genetics*
  • Candida albicans / metabolism*
  • Cluster Analysis
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal*
  • Gene Regulatory Networks*
  • Nitrogen / metabolism*
  • Protein Biosynthesis
  • Transcription, Genetic

Substances

  • Amino Acid Transport Systems
  • Amino Acids
  • Nitrogen

Grants and funding

This work was supported by the German Federal Ministry of Education and Health (BMBF) Germany, FKZ: 01EO1002 - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC, www.cscc.uniklinikum-jena.de). SR was supported by the excellent graduate school Jena School for Microbial Communication (JSMC; www.jsmc.uni-jena.de). JL was supported by the Deutsche Forschungsgemeinschaft (DFG, www.dfg.de) CRC/Transregio 124 ‘Pathogenic fungi and their human host: Networks of interaction’, subproject INF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.