A low gastric pH mouse model to evaluate live attenuated bacterial vaccines

Karen E. Brenneman, Crystal Willingham, Jacquelyn A. Kilbourne, Roy Curtiss, Kenneth L. Roland

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The low pH of the stomach serves as a barrier to ingested microbes and must be overcome or bypassed when delivering live bacteria for vaccine or probiotic applications. Typically, the impact of stomach acidity on bacterial survival is evaluated in vitro, as there are no small animal models to evaluate these effects in vivo. To better understand the effect of this low pH barrier to live attenuated Salmonella vaccines, which are often very sensitive to low pH, we investigated the value of the histamine mouse model for this application. A low pH gastric compartment was transiently induced in mice by the injection of histamine. This resulted in a gastric compartment of approximately pH 1.5 that was capable of distinguishing between acid-sensitive and acid-resistant microbes. Survival of enteric microbes during gastric transit in this model directly correlated with their in vitro acid resistance. Because many Salmonella enterica serotype Typhi vaccine strains are sensitive to acid, we have been investigating systems to enhance the acid resistance of these bacteria. Using the histamine mouse model, we demonstrate that the in vivo survival of S. Typhi vaccine strains increased approximately 10-fold when they carried a sugar-inducible arginine decarboxylase system. We conclude that this model will be a useful for evaluating live bacterial preparations prior to clinical trials.

Original languageEnglish (US)
Article numbere87411
JournalPLoS One
Volume9
Issue number1
DOIs
StatePublished - Jan 29 2014

Fingerprint

Bacterial Vaccines
Attenuated Vaccines
live vaccines
Stomach
stomach
animal models
histamine
Acids
Acid resistance
Histamine
vaccines
acid tolerance
Vaccines
microorganisms
acids
Bacteria
Salmonella Vaccines
arginine decarboxylase
Salmonella Typhi
Salmonella

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Brenneman, K. E., Willingham, C., Kilbourne, J. A., Curtiss, R., & Roland, K. L. (2014). A low gastric pH mouse model to evaluate live attenuated bacterial vaccines. PLoS One, 9(1), [e87411]. https://doi.org/10.1371/journal.pone.0087411

A low gastric pH mouse model to evaluate live attenuated bacterial vaccines. / Brenneman, Karen E.; Willingham, Crystal; Kilbourne, Jacquelyn A.; Curtiss, Roy; Roland, Kenneth L.

In: PLoS One, Vol. 9, No. 1, e87411, 29.01.2014.

Research output: Contribution to journalArticle

Brenneman, KE, Willingham, C, Kilbourne, JA, Curtiss, R & Roland, KL 2014, 'A low gastric pH mouse model to evaluate live attenuated bacterial vaccines', PLoS One, vol. 9, no. 1, e87411. https://doi.org/10.1371/journal.pone.0087411
Brenneman KE, Willingham C, Kilbourne JA, Curtiss R, Roland KL. A low gastric pH mouse model to evaluate live attenuated bacterial vaccines. PLoS One. 2014 Jan 29;9(1). e87411. https://doi.org/10.1371/journal.pone.0087411
Brenneman, Karen E. ; Willingham, Crystal ; Kilbourne, Jacquelyn A. ; Curtiss, Roy ; Roland, Kenneth L. / A low gastric pH mouse model to evaluate live attenuated bacterial vaccines. In: PLoS One. 2014 ; Vol. 9, No. 1.
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