Mutations in bacterial genes induce unanticipated changes in the relationship between bacterial pathogens in experimental otitis media

Abstract

Otitis media (OM) is a common polymicrobial infection of the middle ear in children under the age of 15 years. A widely used experimental strategy to analyse roles of specific phenotypes of bacterial pathogens of OM is to study changes in co-infection kinetics of bacterial populations in animal models when a wild-type bacterial strain is replaced by a specific isogenic mutant strain in the co-inoculating mixtures. As relationships between the OM bacterial pathogens within the host are regulated by many interlinked processes, connecting the changes in the co-infection kinetics to a bacterial phenotype can be challenging. We investigated middle ear co-infections in adult chinchillas (Chinchilla lanigera) by two major OM pathogens: non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat), as well as isogenic mutant strains in each bacterial species. We analysed the infection kinetic data using Lotka – Volterra population dynamics, maximum entropy inference and Akaike information criteria-(AIC)based model selection. We found that changes in relationships between the bacterial pathogens that were not anticipated in the design of the co-infection experiments involving mutant strains are common and were strong