Modeling of Biofilm Formation by Nontypeable Haemophilus influenzae .

Biofilms formed by nontypeable (NTHI) bacteria play an important role in multiple respiratory tract diseases. Visual inspection of the morphology of biofilms formed during chronic infections shows distinct differences from biofilms formed To better understand these differences, we analyzed images of NTHI biofilms formed in the middle ears of and developed an agent-based model of the formation of NTHI biofilms We found that, as , NTHI bacteria are organized in self-similar patterns; however, the sizes of NTHI clusters are more than 10-fold smaller than their counterparts. The agent-based model reproduced these patterns and suggested that smaller clusters occur due to elimination of planktonic NTHI cells by the host responses. Estimation of model parameters by fitting simulation results to imaging data showed that the effects of several processes in the model change during the course of the infection. Multiple respiratory illnesses are associated with formation of biofilms within the human airway by NTHI. However, a substantial amount of our understanding of the mechanisms that underlie NTHI biofilm formation is obtained from studies. Our model that describes biofilm formation by NTHI within the middle ears of will help isolate processes potentially responsible for the differences between the morphologies of biofilms formed versus those formed Thus, the model can be used to glean mechanisms that underlie biofilm formation and connect those mechanisms to those obtained from experiments. The model developed here can be extended to investigate potential roles of specific host responses (e.g., mucociliary clearance) on NTHI biofilm formation The developed computational tools can also be used to analyze and describe biofilm formation by other bacterial species .