E.coli Nissle increases transcription of flagella assembly and formate hydrogenlyase genes in response to colitis

Gut Microbes. 2021 Jan-Dec;13(1):1994832. doi: 10.1080/19490976.2021.1994832.

Abstract

Escherichia coli Nissle (EcN), a probiotic bacterium, has been employed in treating inflammatory bowel disease, but the nature of its therapeutic effect is not fully understood. Intestinal inflammation alters the environment, exposing the microbial population to new stresses and eliciting transcriptional responses. We administered EcN to germ-free mice and then compared its transcriptional response between DSS-treated and untreated conditions using RNA-seq analysis to identify 187 differentially expressed genes (119 upregulated, 68 downregulated) and verifying a subset with qRT-PCR. The upregulated genes included many involved in flagella biosynthesis and motility, as well as several members of the formate hydrogenlyase complex. Despite prior evidence that these pathways are both transcriptionally regulated by nitric oxide, in vitro tests did not establish that nitric oxide exposure alone elicited the transcriptional response. The results provide new information on the transcriptional response of EcN to inflammation and establish a basis for further investigation of its anti-inflammatory activity.

Keywords: Escherichia coli Nissle; RNA-seq; differential transcription; inflammatory bowel disease; intestinal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / microbiology
  • Dextran Sulfate / adverse effects
  • Escherichia coli / enzymology
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Female
  • Flagella / genetics*
  • Flagella / metabolism
  • Formate Dehydrogenases / genetics*
  • Formate Dehydrogenases / metabolism
  • Humans
  • Hydrogenase / genetics*
  • Hydrogenase / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Multienzyme Complexes / genetics*
  • Multienzyme Complexes / metabolism
  • Probiotics / administration & dosage*

Substances

  • Escherichia coli Proteins
  • Multienzyme Complexes
  • Dextran Sulfate
  • Hydrogenase
  • Formate Dehydrogenases
  • formate hydrogenlyase

Grants and funding

This work was supported by the New Frontiers in Research Fund (Canada) [RGPIN-2017-06795, NFRFE-2019-00742], the Canada First Research Excellence Fund [Medicine by Design grant C1TPA-2016-10], and the Natural Sciences and Engineering Research Council (NSERC) (Canada) [NSERC Postgraduate Scholarship].