title: Stress response regulators identified through genome-wide transcriptome analysis of the (p)ppGpp-dependent response in Rhizobium etli.
abstract: BACKGROUND
  The alarmone (p)ppGpp mediates a global reprogramming of gene expression upon nutrient limitation and other stresses to cope with these unfavorable conditions. Synthesis of (p)ppGpp is, in most bacteria, controlled by RelA/SpoT (Rsh) proteins. The role of (p)ppGpp has been characterized primarily in Escherichia coli and several Gram-positive bacteria. Here, we report the first in-depth analysis of the (p)ppGpp-regulon in an α-proteobacterium using a high-resolution tiling array to better understand the pleiotropic stress phenotype of a relA/rsh mutant.
  
  
  RESULTS
  We compared gene expression of the Rhizobium etli wild type and rsh (previously rel) mutant during exponential and stationary phase, identifying numerous (p)ppGpp targets, including small non-coding RNAs. The majority of the 834 (p)ppGpp-dependent genes were detected during stationary phase. Unexpectedly, 223 genes were expressed (p)ppGpp-dependently during early exponential phase, indicating the hitherto unrecognized importance of (p)ppGpp during active growth. Furthermore, we identified two (p)ppGpp-dependent key regulators for survival during heat and oxidative stress and one regulator putatively involved in metabolic adaptation, namely extracytoplasmic function sigma factor EcfG2/PF00052, transcription factor CH00371, and serine protein kinase PrkA.
  
  
  CONCLUSIONS
  The regulatory role of (p)ppGpp in R. etli stress adaptation is far-reaching in redirecting gene expression during all growth phases. Genome-wide transcriptome analysis of a strain deficient in a global regulator, and exhibiting a pleiotropic phenotype, enables the identification of more specific regulators that control genes associated with a subset of stress phenotypes. This work is an important step toward a full understanding of the regulatory network underlying stress responses in α-proteobacteria.
authors.affiliation: Centre of Microbial and Plant Genetics, Katholiek Universiteit Leuven, Kasteelpark Arenberg 20, 3001 Heverlee, Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Vercruysse
authors.forename: Maarten
authors.initials: M
authors.lastname: Fauvart
authors.forename: Ann
authors.initials: A
authors.lastname: Jans
authors.forename: Serge
authors.initials: S
authors.lastname: Beullens
authors.forename: Kristien
authors.initials: K
authors.lastname: Braeken
authors.forename: Lore
authors.initials: L
authors.lastname: Cloots
authors.forename: Kristof
authors.initials: K
authors.lastname: Engelen
authors.forename: Kathleen
authors.initials: K
authors.lastname: Marchal
authors.forename: Jan
authors.initials: J
authors.lastname: Michiels
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D006158:Guanosine Pentaphosphate / Q000235:genetics / Q000378:metabolism*; D006159:Guanosine Tetraphosphate / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D058727:RNA, Small Untranslated; D042163:Rhizobium etli / Q000235:genetics* / Q000254:growth & development; D013312:Stress, Physiological / Q000235:genetics*; D059467:Transcriptome
chemical_list: D001426:Bacterial Proteins; D058727:RNA, Small Untranslated; D006159:Guanosine Tetraphosphate; D006158:Guanosine Pentaphosphate