title: Multi-level evaluation of Escherichia coli polyphosphate related mutants using global transcriptomic, proteomic and phenomic analyses.
abstract: Polyphosphate (polyP) is a linear biopolymer found in all living cells. In bacteria, mutants lacking polyphosphate kinase 1 (PPK1), the enzyme responsible for synthesis of most polyP, have many structural and functional defects. However, little is known about the causes of these pleiotropic alterations. The link between ppk1 deletion and those numerous phenotypes observed can be the result of complex molecular interactions that can be elucidated via a systems biology approach.
  
  
  
  By integrating different omics levels (transcriptome, proteome and phenome), we described the functioning of various metabolic pathways among Escherichia coli polyphosphate mutant strains (Δppk1, Δppx, and ΔpolyP). Bioinformatic analyses reveal the complex metabolic and regulatory bases of the phenotypes unique to polyP mutants.
  
  
  
  Our results suggest that during polyP deficiency (Δppk1 mutant), metabolic pathways needed for energy supply are up-regulated, including fermentation, aerobic and anaerobic respiration. Transcriptomic and q-proteomic contrasting changes between Δppk1 and Δppx mutant strains were observed in those central metabolic pathways and confirmed by using Phenotypic microarrays. In addition, our results suggest a regulatory connection between polyP, second messenger metabolism, alternative Sigma/Anti-Sigma factors and type-II toxin-antitoxin (TA) systems.
  
  
  
  We suggest a broader role for polyP via regulation of ATP-dependent proteolysis of type II toxin-antitoxin system and alternative Sigma/Anti-Sigma factors, that could explain the multiple structural and functional deficiencies described due to alteration of polyP metabolism.
  
  
  
  Understanding the interplay of polyP in bacterial metabolism using a systems biology approach can help to improve design of novel antimicrobials toward pathogens.
authors.affiliation: Systems Microbiology Laboratory, Department of Biology, Faculty of Science, University of Chile, Chile. Electronic address: mvaras26@gmail.com.
authors.forename: Macarena
authors.initials: M
authors.lastname: Varas
authors.affiliation: Systems Microbiology Laboratory, Department of Biology, Faculty of Science, University of Chile, Chile; Department of Ecology, Faculty of Science, University of Chile, Chile. Electronic address: c.valdivieso.guerrero@gmail.com.
authors.forename: Camilo
authors.initials: C
authors.lastname: Valdivieso
authors.affiliation: Systems Microbiology Laboratory, Department of Biology, Faculty of Science, University of Chile, Chile. Electronic address: cmauriaca@gmail.com.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mauriaca
authors.affiliation: Systems Microbiology Laboratory, Department of Biology, Faculty of Science, University of Chile, Chile. Electronic address: javiera.o.s@gmail.com.
authors.forename: Javiera
authors.initials: J
authors.lastname: Ortíz-Severín
authors.affiliation: Proteomic Service, CNB CSIC, Spain. Electronic address: alberto.paradela@cnb.csic.es.
authors.forename: Alberto
authors.initials: A
authors.lastname: Paradela
authors.affiliation: Facultad de Ciencias Biológicas, Center for Bioinformatics and Integrative Biology, Biosystems Engineering Laboratory, Universidad Andrés Bello, Chile. Electronic address: ignacio.poblete@unab.cl.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Poblete-Castro
authors.affiliation: Department of Biology, Faculty of Sciences, University of Chile, Chile. Electronic address: rcabrer@uchile.cl.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Cabrera
authors.affiliation: Systems Microbiology Laboratory, Department of Biology, Faculty of Science, University of Chile, Chile. Electronic address: fpchavez@uchile.cl.
authors.forename: Francisco P
authors.initials: FP
authors.lastname: Chávez
mesh_terms: D000992:Antitoxins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019069:Cell Respiration / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics; D005285:Fermentation / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011122:Polyphosphates / Q000378:metabolism*; D020543:Proteome / Q000235:genetics*; D040901:Proteomics / Q000379:methods; D012808:Sigma Factor / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000992:Antitoxins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D011122:Polyphosphates; D020543:Proteome; D012808:Sigma Factor; D017853:Phosphotransferases (Alcohol Group Acceptor); C475691:polyphosphate kinase, E coli
keywords: Omics; Phenotypic microarray; PolyP-dependent proteolysis; Polyphosphate; Q-proteomics; Systems Biology