Quantifying bacterial fitness in intracellular dynamics

Abstract

Understanding bacterial infection is challenging because it involves a complex interplay of host, pathogen, and intervention factors. To design successful control measures, mathematical models that quantify such interplay at the level of populations and phenotypes are needed. Here, we study a key aspect of intracellular infection: the interaction dynamics between bacteria and target cells, applicable to pathogens such as Salmonella, E. coli or Listeria monocytogenes. Our mathematical model focuses on the macrophage-bacteria system, implicitly accounting for host immunity, and illustrates three infection scenarios driven by the balance between bacterial growth and death processes. Our analysis reveals critical parameter combinations for the intracellular vs. extracellular fitness advantage of persistent bacteria, and the drivers of overall infection success across acute and persistent regimes. Our results provide quantitative insights on transitions from persistent, to acute, to containment of infection, and suggest biological parameters, such as infected macrophage apoptosis rate and burst size, as suitable intervention targets.