Helicobacter pylori Biofilm Involves a Multigene Stress-Biased Response, Including a Structural Role for Flagella

mBio. 2018 Oct 30;9(5):e01973-18. doi: 10.1128/mBio.01973-18.

Abstract

Helicobacter pylori has an impressive ability to persist chronically in the human stomach. Similar characteristics are associated with biofilm formation in other bacteria. The H. pylori biofilm process, however, is poorly understood. To gain insight into this mode of growth, we carried out comparative transcriptomic analysis between H. pylori biofilm and planktonic cells, using the mouse-colonizing strain SS1. Optimal biofilm formation was obtained with a low concentration of serum and 3 days of growth, conditions that caused both biofilm and planktonic cells to be ∼80% coccoid. Transcriptome sequencing (RNA-seq) analysis found that 8.18% of genes were differentially expressed between biofilm and planktonic cell transcriptomes. Biofilm-downregulated genes included those involved in metabolism and translation, suggesting these cells have low metabolic activity. Biofilm-upregulated genes included those whose products were predicted to be at the cell envelope, involved in regulating a stress response, and surprisingly, genes related to formation of the flagellar apparatus. Scanning electron microscopy visualized flagella that appeared to be a component of the biofilm matrix, supported by the observation that an aflagellated mutant displayed a less robust biofilm with no apparent filaments. We observed flagella in the biofilm matrix of additional H. pylori strains, supporting that flagellar use is widespread. Our data thus support a model in which H. pylori biofilm involves a multigene stress-biased response and that flagella play an important role in H. pylori biofilm formation.IMPORTANCE Biofilms, communities of bacteria that are embedded in a hydrated matrix of extracellular polymeric substances, pose a substantial health risk and are key contributors to many chronic and recurrent infections. Chronicity and recalcitrant infections are also common features associated with the ulcer-causing human pathogen H. pylori However, relatively little is known about the role of biofilms in H. pylori pathogenesis, as well as the biofilm structure itself and the genes associated with this mode of growth. In the present study, we found that H. pylori biofilm cells highly expressed genes related to cell envelope and stress response, as well as those encoding the flagellar apparatus. Flagellar filaments were seen in high abundance in the biofilm. Flagella are known to play a role in initial biofilm formation, but typically are downregulated after that state. H. pylori instead appears to have coopted these structures for nonmotility roles, including a role building a robust biofilm.

Keywords: Helicobacter pylori; RNA-seq; biofilm; flagella; metabolism; stress; stress response; transcriptome; transcriptomics.

Publication types

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

MeSH terms

  • Biofilms / growth & development*
  • Flagella / metabolism*
  • Flagella / ultrastructure
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial*
  • Helicobacter pylori / growth & development
  • Helicobacter pylori / physiology*
  • Helicobacter pylori / ultrastructure
  • Metabolic Networks and Pathways / genetics
  • Microscopy, Electron, Scanning
  • Sequence Analysis, RNA
  • Stress, Physiological*