Presentation Title: MYCOBACTERIUM AVIUM INFECTION IN THE LUNGS: An Agent-based model showing the Effects of Bacterial Phenotypes and Biofilm
Author Name(s): 1Catherine Weathered*, 2Patricio Escalante, 2Kelly Pennington, 1Elsje Pienaar
Author Department and School Affiliation: 1Purdue University, West Lafayette, IN, USA; 2Mayo Clinic, Rochester, MN, USA
Abstract: Mycobacterium avium complex (MAC), a type of nontuberculous mycobacteria, are environmental microbes, capable of colonizing and infecting humans following inhalation of the bacteria. We hypothesize a balance of bacterial factors (phenotypic diversity and biofilm formation) and host
immune factors (speed and magnitude of response) is key to establishing and prolonging these notoriously difficult to treat infections in the lung. To test these hypotheses, we developed a 3D agentbased model (ABM) that incorporates known interactions between bacteria, biofilm and immune cells in virtual lung tissue.
Model results show an early relationship between the initial number of macrophages or distance that chemoattractants diffuse, and the ratio of planktonic to sessile bacteria. Though larger initial macrophage numbers result in a stronger reduction in planktonic bacteria early after infection, sessile bacteria within biofilms and infected macrophages can sustain the bacterial population, allowing the planktonic population to recover. This effect is offset with further chemoattract diffusion, as the macrophages can clear the infection early or recruit more macrophages. Thus, the model predicts that both bacterial phenotypes and a suppressed immune response affect the bacterial ability to survive, propagate, and establish infections. Future directions include adding drug pharmacodynamics and the role of phenotypes in cell-level pharmacodynamics