High-resolution mapping reveals that microniches in the gastric glands control Helicobacter pylori colonization of the stomach

Connie Fung, Shumin Tan, Mifuyu Nakajima, Emma C. Skoog, Luis Fernando Camarillo-Guerrero, Jessica A. Klein, Trevor D. Lawley, Jay V Solnick, Tadashi Fukami, Manuel R. Amieva

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Lifelong infection of the gastric mucosa by Helicobacter pylori can lead to peptic ulcers and gastric cancer. However, how the bacteria maintain chronic colonization in the face of constant mucus and epithelial cell turnover in the stomach is unclear. Here, we present a new model of how H. pylori establish and persist in stomach, which involves the colonization of a specialized microenvironment, or microniche, deep in the gastric glands. Using quantitative three-dimensional (3D) confocal microscopy and passive CLARITY technique (PACT), which renders tissues optically transparent, we analyzed intact stomachs from mice infected with a mixture of isogenic, fluorescent H. pylori strains with unprecedented spatial resolution. We discovered that a small number of bacterial founders initially establish colonies deep in the gastric glands and then expand to colonize adjacent glands, forming clonal population islands that persist over time. Gland-associated populations do not intermix with free-swimming bacteria in the surface mucus, and they compete for space and prevent newcomers from establishing in the stomach. Furthermore, bacterial mutants deficient in gland colonization are outcompeted by wild-type (WT) bacteria. Finally, we found that host factors such as the age at infection and T-cell responses control bacterial density within the glands. Collectively, our results demonstrate that microniches in the gastric glands house a persistent H. pylori reservoir, which we propose replenishes the more transient bacterial populations in the superficial mucosa.

Original languageEnglish (US)
Pages (from-to)e3000231
JournalPLoS biology
Volume17
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Helicobacter pylori
gastric mucosa
Gastric Mucosa
Stomach
Bacteria
stomach
Mucus
mucus
bacteria
T-cells
Confocal microscopy
Population
peptic ulcers
stomach neoplasms
Infection
Peptic Ulcer
Islands
Confocal Microscopy
infection
Tissue

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Fung, C., Tan, S., Nakajima, M., Skoog, E. C., Camarillo-Guerrero, L. F., Klein, J. A., ... Amieva, M. R. (2019). High-resolution mapping reveals that microniches in the gastric glands control Helicobacter pylori colonization of the stomach. PLoS biology, 17(5), e3000231. https://doi.org/10.1371/journal.pbio.3000231

High-resolution mapping reveals that microniches in the gastric glands control Helicobacter pylori colonization of the stomach. / Fung, Connie; Tan, Shumin; Nakajima, Mifuyu; Skoog, Emma C.; Camarillo-Guerrero, Luis Fernando; Klein, Jessica A.; Lawley, Trevor D.; Solnick, Jay V; Fukami, Tadashi; Amieva, Manuel R.

In: PLoS biology, Vol. 17, No. 5, 01.05.2019, p. e3000231.

Research output: Contribution to journalArticle

Fung, C, Tan, S, Nakajima, M, Skoog, EC, Camarillo-Guerrero, LF, Klein, JA, Lawley, TD, Solnick, JV, Fukami, T & Amieva, MR 2019, 'High-resolution mapping reveals that microniches in the gastric glands control Helicobacter pylori colonization of the stomach', PLoS biology, vol. 17, no. 5, pp. e3000231. https://doi.org/10.1371/journal.pbio.3000231
Fung, Connie ; Tan, Shumin ; Nakajima, Mifuyu ; Skoog, Emma C. ; Camarillo-Guerrero, Luis Fernando ; Klein, Jessica A. ; Lawley, Trevor D. ; Solnick, Jay V ; Fukami, Tadashi ; Amieva, Manuel R. / High-resolution mapping reveals that microniches in the gastric glands control Helicobacter pylori colonization of the stomach. In: PLoS biology. 2019 ; Vol. 17, No. 5. pp. e3000231.
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