Polyphosphate binds to the principal sigma factor of RNA polymerase during starvation response in Helicobacter pylori

Mol Microbiol. 2010 Aug;77(3):618-27. doi: 10.1111/j.1365-2958.2010.07233.x. Epub 2010 Jun 11.


Helicobacter pylori persists deep in the human gastric mucus layer in a harsh, nutrient-poor environment. Survival under these conditions depends on the ability of this human pathogen to invoke starvation/stress responses when needed. Unlike many bacteria, H. pylori lacks starvation/stress-responding alternative sigma factors, suggesting an additional mechanism might have evolved in this bacterium. Helicobacter pylori produces polyphosphate; however, the role and target of polyphosphate during starvation/stress have not been identified. Here we show that polyphosphate accumulated during nutrient starvation directly targets transcriptional machinery by binding to the principal sigma factor in H. pylori, uncovering a novel mechanism in microbial stress response. A positively charged Lys-rich region at the N-terminal domain of the major sigma factor is identified as the binding region for polyphosphate (region P) in vivo and in vitro, revealing a new element in sigma 70 family proteins. This interaction is biologically significant because mutant strains defective in the interaction undergo premature cell death during starvation. We suggested that polyphosphate is a second messenger employed by H. pylori to mediate gene expression during starvation/stress. The putative 'region P' is present in sigma factors of other human pathogens, suggesting that the uncovered interaction might be a general strategy employed by other pathogens.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • DNA-Directed RNA Polymerases / chemistry
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism*
  • Gene Expression Regulation, Bacterial
  • Helicobacter pylori / chemistry
  • Helicobacter pylori / genetics
  • Helicobacter pylori / metabolism*
  • Molecular Sequence Data
  • Polyphosphates / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Sigma Factor / chemistry
  • Sigma Factor / genetics
  • Sigma Factor / metabolism*


  • Bacterial Proteins
  • Polyphosphates
  • Sigma Factor
  • RNA polymerase sigma 70
  • DNA-Directed RNA Polymerases