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 fifteen years. A widely used experimental strategy to analyze 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. Since 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: nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat), as well as isogenic mutant strains in each bacterial species. We analyzed 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 regulators of the co-infecting bacterial populations. The framework developed here allows for a systematic analysis of host-host variations of bacterial populations and small sizes of animal cohorts in coinfection experiments to quantify the role of specific mutant strains in changing the infection kinetics. Our combined approach can be used to analyze the functional footprint of mutant strains in regulating co-infection kinetics in models of experimental OM and other polymicrobial diseases.

Panel 4: Recent advances in understanding the natural history of the otitis media microbiome and its response to environmental pressures

“…Additionally, it is important to note that new research continues to characterize the effects of microbial interactions on the multispecies bacterial biofilms implicated in middle ear infections, e.g. S. pneumoniae and nontypeable H. influenzae (NTHi) [101,102]; NTHi and M. catarrhalis [103,104]; and NTHi and Alloiococcus otitidis [105], although a role for the latter in OM is unclear.…”

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

“…The in vivo datasets and the Matlab code used to analyse the data are available at Dryad Digital Repository: [35].…”