Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration

Alanna M. Spees, Tamding Wangdi, Christopher A. Lopez, Dawn D. Kingsbury, Mariana N. Xavier, Sebastian E. Winter, Renée M. Tsolis, Andreas J. Bäumler

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Treatment with streptomycin enhances the growth of human commensal Escherichia coli isolates in the mouse intestine, suggesting that the resident microbial community (microbiota) can inhibit the growth of invading microbes, a phenomenon known as "colonization resistance." However, the precise mechanisms by which streptomycin treatment lowers colonization resistance remain obscure. Here we show that streptomycin treatment rendered mice more susceptible to the development of chemically induced colitis, raising the possibility that the antibiotic might lower colonization resistance by changing mucosal immune responses rather than by preventing microbe-microbe interactions. Investigation of the underlying mechanism revealed a mild inflammatory infiltrate in the cecal mucosa of streptomycin-treated mice, which was accompanied by elevated expression of Nos2, the gene that encodes inducible nitric oxide synthase. In turn, this inflammatory response enhanced the luminal growth of E. coli by nitrate respiration in a Nos2-dependent fashion. These data identify low-level intestinal inflammation as one of the factors responsible for the loss of resistance to E. coli colonization after streptomycin treatment. IMPORTANCE Our intestine is host to a complex microbial community that confers benefits by educating the immune system and providing niche protection. Perturbation of intestinal communities by streptomycin treatment lowers "colonization resistance" through unknown mechanisms. Here we show that streptomycin increases the inflammatory tone of the intestinal mucosa, thereby making the bowel more susceptible to dextran sulfate sodium treatment and boosting the Nos2-dependent growth of commensal Escherichia coli by nitrate respiration. These data point to the generation of alternative electron acceptors as a byproduct of the inflammatory host response as an important factor responsible for lowering resistance to colonization by facultative anaerobic bacteria such as E. coli.

Original languageEnglish (US)
JournalmBio
Volume4
Issue number4
DOIs
StatePublished - Jul 2 2013

Fingerprint

Streptomycin
Nitrates
Respiration
Escherichia coli
Inflammation
Growth
Intestines
Mucosal Immunity
Dextran Sulfate
Anaerobic Bacteria
Microbiota
Nitric Oxide Synthase Type II
Colitis
Intestinal Mucosa
Immune System
Mucous Membrane
Electrons
Anti-Bacterial Agents
Gene Expression

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Spees, A. M., Wangdi, T., Lopez, C. A., Kingsbury, D. D., Xavier, M. N., Winter, S. E., ... Bäumler, A. J. (2013). Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration. mBio, 4(4). https://doi.org/10.1128/mBio.00430-13

Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration. / Spees, Alanna M.; Wangdi, Tamding; Lopez, Christopher A.; Kingsbury, Dawn D.; Xavier, Mariana N.; Winter, Sebastian E.; Tsolis, Renée M.; Bäumler, Andreas J.

In: mBio, Vol. 4, No. 4, 02.07.2013.

Research output: Contribution to journalArticle

Spees, AM, Wangdi, T, Lopez, CA, Kingsbury, DD, Xavier, MN, Winter, SE, Tsolis, RM & Bäumler, AJ 2013, 'Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration', mBio, vol. 4, no. 4. https://doi.org/10.1128/mBio.00430-13
Spees, Alanna M. ; Wangdi, Tamding ; Lopez, Christopher A. ; Kingsbury, Dawn D. ; Xavier, Mariana N. ; Winter, Sebastian E. ; Tsolis, Renée M. ; Bäumler, Andreas J. / Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration. In: mBio. 2013 ; Vol. 4, No. 4.
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