The objective of the present study was to develop a mathematical model of pathogenic bacterial inactivation kinetics in a gastric environment in order to further understand a part of the infectious dose-response mechanism. The major bacterial pathogens Listeria monocytogenes, Escherichia coli O157: H7, and Salmonella spp. were examined by using simulated gastric fluid adjusted to various pH values. To correspond to the various pHs in a stomach during digestion, a modified logistic differential equation model and the Weibull differential equation model were examined. The specific inactivation rate for each pathogen was successfully described by a square-root model as a function of pH. The square-root models were combined with the modified logistic differential equation to obtain a complete inactivation curve. Both the modified logistic and Weibull models provided a highly accurate fitting of the static pH conditions for every pathogen. However, while the residuals plots of the modified logistic model indicated no systematic bias and/or regional prediction problems, the residuals plots of the Weibull model showed a systematic bias. The modified logistic model appropriately predicted the pathogen behavior in the simulated gastric digestion process with actual food, including cut lettuce, minced tuna, hamburger, and scrambled egg. Although the developed model enabled us to predict pathogen inactivation during gastric digestion, its results also suggested that the ingested bacteria in the stomach would barely be inactivated in the real digestion process. The results of this study will provide important information on a part of the dose-response mechanism of bacterial pathogens.Dose-response models play an important role in characterizing the risk in quantitative microbial risk assessments (15). The currently available dose-response models of microbial risk assessment are derived from the following different source data: human-feeding volunteer tests (14), extrapolation of the results of animal experiments to humans (44, 51), and estimations from epidemiological studies of outbreaks of food-borne illness (8). However, these approaches to dose-response modeling of low-dose exposures to pathogens rely on multiple assumptions and extrapolations, which reflect the current lack of knowledge regarding the fundamental mechanisms underlying the responses to a dose (10).Recently, a new concept, called the key-events dose-response framework (KEDRF), has been introduced as an alternative approach for the development of dose-response models (10). In the KEDRF approach, the following five major and necessary steps, termed key events, are proposed: (i) survival of pathogens in the upper gastrointestinal tract, (ii) establishment in the intestine and attachment to and uptake into epithelial cells, (iii) survival and escape from phagosomes in enterocytes and transfer of pathogen to phagocytes, (iv) transfer of pathogens across placenta, and (v) pathogen growth leading to fetal morbidity and mortality.At each step, the ranges of facto...