Integrating mathematical models with experimental data to investigate the within-host dynamics of bacterial...

Bacterial infections still constitute a major cause of mortality and morbidity worldwide. The unavailability of therapeutics, antimicrobial resistance and the chronicity of infections due to incomplete clearance contribute to this phenomenon. Despite the progress in antimicrobial and vaccine development, knowledge about the effect that therapeutics have on the host-bacteria interactions remains incomplete. Insights into the characteristics of bacterial colonization and migration between tissues and the relationship between replication and host- or therapeutically induced killing can enable efficient design of treatment approaches. Recently, innovative experimental techniques have generated data enabling the qualitative characterization of aspects of bacterial dynamics. Here, we argue that mathematical modeling as an adjunct to experimental data can enrich the biological insight that these data provide. However, due to limited interdisciplinary training, efforts to combine the two remain limited. To promote this dialogue, we provide a categorization of modeling approaches highlighting their relationship to data generated by a range of experimental techniques in the area of in vivo bacterial dynamics. We outline common biological themes explored using mathematical models with case studies across all pathogen classes. Finally, this review advocates multidisciplinary integration to improve our mechanistic understanding of bacterial infections and guide the use of existing or new therapies.