Competitive growth kinetics of Campylobacter jejuni, Escherichia coli O157:H7 and Listeria monocytogenes with enteric microflora in a small-intestine model.

AIMS: The biological events occurring during human digestion help to understand the mechanisms underlying the dose-response relationships of enteric bacterial pathogens. To better understand these events, we investigated the growth and reduction behaviour of bacterial pathogens in an in vitro model simulating the environment of the small intestine. METHODS AND RESULTS: The foodborne pathogens Campylobacter jejuni, Listeria monocytogenes and Escherichia coli O157:H7 were cultured with multiple competing enteric bacteria. Differences in the pathogen's growth kinetics due to the relative amount of competing enteric bacteria were investigated. These growth differences were described using a mathematical model based on Bayesian inference. When pathogenic and enteric bacteria were inoculated at 1 log CFU per ml and 9 log CFU per ml, respectively, L. monocytogenes was inactivated over time, while C. jejuni and E. coli O157:H7 survived without multiplying. However, as pathogen inocula were increased, its inhibition by enteric bacteria also decreased. CONCLUSIONS: Although the growth of pathogenic species was inhibited by enteric bacteria, the pathogens still survived. SIGNIFICANCE AND IMPACT OF THE STUDY: Competition experiments in a small-intestine model have enhanced understanding of the infection risk in the intestine and provide insights for evaluating dose-response relationships.

A New Dose-Response Model for Estimating the Infection Probability of Campylobacter jejuni Based on the Key Events Dose-Response Framework.

Understanding the dose-response relationship between ingested pathogenic bacteria and infection probability is a key factor for appropriate risk assessment of foodborne pathogens. The objectives of this study were to develop and validate a novel mechanistic dose-response model for Campylobacter jejuni and simulate the underlying mechanism of foodborne illness during digestion. Bacterial behavior in the human gastrointestinal environment, including survival at low pH in the gastric environment after meals, transition to intestines, and invasion to intestinal tissues, was described using a Bayesian statistical model based on the reported experimental results of each process while considering physical food types (liquid versus solid) and host age (young adult versus elderly). Combining the models in each process, the relationship between pathogen intake and the infection probability of C. jejuni was estimated and compared with reported epidemiological dose-response relationships. Taking food types and host age into account, the prediction range of the infection probability of C. jejuni successfully covered the reported dose-response relationships from actual C. jejuni outbreaks. According to sensitivity analysis of predicted infection probabilities, the host age factor and the food type factor have relatively higher relevance than other factors. Thus, the developed "key events dose-response framework" can derive novel information for quantitative microbiological risk assessment in addition to dose-response relationship. The framework is potentially applicable to other pathogens to quantify the dose-response relationship from experimental data obtained from digestion. IMPORTANCE Based on the mechanistic approach called the key events dose-response framework (KEDRF), an alternative to previous nonmechanistic approaches, the dose-response models for infection probability of C. jejuni were developed considering with age of people who ingest pathogen and food type. The developed predictive framework illustrates highly accurate prediction of dose (minimum difference 0.21 log CFU) for a certain infection probability compared with the previously reported dose-response relationship. In addition, the developed prediction procedure revealed that the dose-response relationship strongly depends on food type as well as host age. The implementation of the key events dose-response framework will mechanistically and logically reveal the dose-response relationship and provide useful information with quantitative microbiological risk assessment of C. jejuni on foods.