UC Irvine

Dose-response models (DRMs) are used to predict the probability of microbial infection when a person is exposed to a given number of pathogens. In this study, we propose a new DRM for Staphylococcus aureus (SA), which causes skin and soft-tissue infections. The current approach to SA dose-response is only partially mechanistic and assumes that individual bacteria do not interact with each other. Our proposed two-compartment (2C) model assumes that bacteria that have not adjusted to the host environment decay. After adjusting to the host, they exhibit logistic/cooperative growth, eventually causing disease. The transition between the adjusted and un-adjusted states is a stochastic process, which the 2C DRM explicitly models to predict response probabilities. By fitting the 2C model to SA pathogenesis data, we show that cooperation between individual SA bacteria is sufficient (and, within the scope of the 2C model, necessary) to characterize the dose-response. This is a departure from the classical single-hit theory of dose-response, where complete independence is assumed between individual pathogens. From a quantitative microbial risk assessment standpoint, the mechanistic basis of the 2C DRM enables transparent modeling of dose-response of antibiotic-resistant SA that has not been possible before. It also enables the modeling of scenarios having multiple/non-instantaneous exposures, with minimal assumptions.