Modeling Bacterial Pathogen Emergence at the Human-Animal Interface: Methicillin-Resistant Staphylococcus aureus ST398 and its Implications for Public Health

Abstract

Over half of all recognized human pathogens are zoonotic in origin––most important human pathogens either continue to spillover from animal reservoirs or “originated as zoonoses before adapting to humans” (Lloyd-Smith et al. 2009). Significantly, antibiotic-resistant bacterial infections currently account for the majority of emerging diseases worldwide with studies over the past decade documenting the key role that nontherapeutic agricultural antibiotic use (AAU) has played in the emergence and spread of resistance (Silbergeld et al. 2008). Methicillin-resistant Staphylococcus aureus (MRSA) ST398, in particular, has evolved extensive multidrug resistance (MDR) as a result of widespread antibiotic use in various livestock (primarily pigs, veal calves and chickens) and was first detected in human populations in the early 2000s. Further empirical studies have confirmed that MRSA ST398 is a highly resistant pathogen currently in the process of a host species jump from livestock to humans. Therefore, as an extension to the stochastic model of pathogen emergence via adaptive evolution developed by Arinaminpathy & McClean (2009), the model created for this study investigates the impact of co-existing pathogen life histories of transient and persistent colonization (based on MRSA ST398) on the pathogen emergence process. The results of this model demonstrate that persistent colonization with particularly long colonization duration facilitates the emergence process and increases the probability of emergence per introduction. Furthermore, the inclusion of a small proportion of persistently colonized hosts increases the size and frequency of large outbreaks before emergence while simultaneously decreasing the frequency of introductions that result in no secondary transmission. With respect to MRSA ST398, the results of the pathogen emergence model demonstrate that MRSA ST398 and pathogens sharing similar co-existing life histories are particularly prone to emergence in novel host populations. The emergence of MRSA ST398, then, could have serious public health implications since its high capacity for horizontal gene transfer (HGT) may lead to the spread of its resistance determinants to various other bacteria populations and species circulating in human populations.