Influence of gastric acid on susceptibility to infection with ingested bacterial pathogens.
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 < OR = 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.
Tennant
Sharon M
SM
Department of Microbiology and Immunology, The University of Melbourne, and Murdoch Children's Research Institute, Royal Children's Hospital, Victoria 3010, Australia.
Hartland
Elizabeth L
EL
Phumoonna
Tongted
T
Lyras
Dena
D
Rood
Julian I
JI
Robins-Browne
Roy M
RM
van Driel
Ian R
IR
D000143:Acids / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D044082:Citrobacter rodentium / Q000187:drug effects; D003015:Clostridium Infections / Q000517:prevention & control*; D003016:Clostridium perfringens / Q000187:drug effects; D015169:Colony Count, Microbial; D004756:Enterobacteriaceae Infections / Q000517:prevention & control*; D005260:Female; D005744:Gastric Acid / Q000502:physiology*; D008099:Liver / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050296:Microbial Viability; D006180:Proton-Translocating ATPases / Q000172:deficiency; D012481:Salmonella Infections, Animal / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000187:drug effects; D013154:Spleen / Q000382:microbiology; D015009:Yersinia Infections / Q000517:prevention & control*; D015008:Yersinia enterocolitica / Q000187:drug effects
D000143:Acids; D000900:Anti-Bacterial Agents; D006180:Proton-Translocating ATPases