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Infection and Immunity, February 2008, p. 639-645, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01138-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Influence of Gastric Acid on Susceptibility to Infection with Ingested Bacterial Pathogens{triangledown}

Sharon M. Tennant,1 Elizabeth L. Hartland,1,2 Tongted Phumoonna,2 Dena Lyras,2 Julian I. Rood,2 Roy M. Robins-Browne,1* and Ian R. van Driel3

Department of Microbiology and Immunology, The University of Melbourne, and Murdoch Children's Research Institute, Royal Children's Hospital, Victoria 3010, Australia,1 Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia,2 Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia3

Received 17 August 2007/ Returned for modification 20 September 2007/ Accepted 6 November 2007

Despite the widely held belief that gastric acid serves as a barrier to bacterial pathogens, there are almost no experimental data to support this hypothesis. We have developed a mouse model to quantify the effectiveness of gastric acid in mediating resistance to infection with ingested bacteria. Mice that were constitutively hypochlorhydric due to a mutation in a gastric H+/K+-ATPase (proton pump) gene were infected with Yersinia enterocolitica, Salmonella enterica serovar Typhimurium, Citrobacter rodentium, or Clostridium perfringens cells or spores. Significantly greater numbers of Yersinia, Salmonella, and Citrobacter cells (P ≤ 0.006) and Clostridium spores (P = 0.02) survived in hypochlorhydric mice, resulting in reduced median infectious doses. Experiments involving intraperitoneal infection or infection of mice treated with antacids indicated that the increased sensitivity of hypochlorhydric mice to infection was entirely due to the absence of stomach acid. Apart from establishing the role of gastric acid in nonspecific immunity to ingested bacterial pathogens, our model provides an excellent system with which to investigate the effects of hypochlorhydria on susceptibility to infection and to evaluate the in vivo susceptibility to gastric acid of orally administered therapies, such as vaccines and probiotics.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia. Phone: 61-3 8344 8275. Fax: 61-3 8344 8276. E-mail: r.browne{at}unimelb.edu.au

{triangledown} Published ahead of print on 19 November 2007.

Editor: R. P. Morrison

Infection and Immunity, February 2008, p. 639-645, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01138-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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