Concurrent Modeling of Bacteria-DNase-Antimicrobial Interactions In Solution
Faculty: Adriana Compagnoni (Stevens), Matthew Libera (Stevens), Karin Sauer (Binghamton University), Svetlana Sukhishvili (Stevens), Philippe Bidinger (Verimag), Eduardo Bonelli (UNQ)
Students: Yifei Bao (Stevens), Vishakha Sharma (Stevens)
Research Overview
Infections are now recognized as a leading cause of failure in implanted biomedical devices. They occur when bacteria colonize a device's biomaterial surface, develop into biofilms (Fig. 1), and infect the surrounding tissue. Bacteria in the biofilm state are orders of magnitude more resistant to antibiotics than bacteria in the planktonic state. Thus, the current practice of systemic delivery of broad spectrum antibiotics ultimately exacerbate the problem by selecting for drug-resistant strains rather than curing the infection. One current clinical practice includes localized rather than systemic delivery of antibacterial agents (AmAs) from inserted delivery reservoirs in the implant area. Yet such treatment is not particularly efficient in preventing post-surgery implant infection, because of the high doses required, the toxicity issues, and the eventual depletion of the drug from the reservoir. Therefore standard clinical practice to deal with infected implanted medical devices is to remove the implant altogether and, when possible, perform a revision surgery with a second implant when the infection has cleared. This, however, has tremendous impact on patient well-being and increases the total cost by an order of magnitude or more. The infection-related failure rate ranges from 0.5% to 4% for hip and knee implants , and it can be as high as 40% for fixation devices used in the treatment of traumatic orthopedic injury. The total cost of this problem to the American health-care system is over $6 billion annually. Therefore, engineering biomaterials whose surfaces prevent bacterial attachment or deliver antibacterial agents in targeted and efficient ways is an important yet unsolved problem, from both the fundamental and the clinical perspectives.
Fig. 1: Biofilm Developmental stages
Biofilms are complex communities of microorganisms attached to surfaces and embedded in a self-produced extracellular matrix. The extracellular matrix (ECM) can constitute up to 90% of the biofilm biomass and provides a hydrated scaffolding to stabilize and reinforce the biofilm structure. The importance of extracellular genomic DNA (eDNA) as a structural component of biofilms was first demonstrated in P. aeruginosa. Whitchurch et al. demonstrated that P. aeruginosa PAO1 biofilm formation was attenuated under static growth conditions and significantly reduced under flowing growth conditions by the presence of DNase in the growth medium.
Modeling
We built a prototype model of bacteria-DNase-antimicrobial interactions in solution. Initial state of simulation starting with twenty irreversibly attached bacteria (green) on surface, sixty drug molecules (blue), and sixty DNAse particles in solution (purple). After a few seconds of computing time, we observe clusters containing external DNA (eDNA) (turquoise), biomass (black), and bacteria (green) representing biofims. DNAse (purple) breaks down eDNA dispersing bacteria (yellow). Dispersed bacteria can multiply, generate eDNA and other biomass, and be killed (red) by drug molecules (blue).
The following is a fragment of BioScape code. DNase breaks eDNA through channel break; eDNA then disperse bound bacteria (bacB) through channel free, generating free bacteria (bacF), while bound bacteria can also multiply, and generate eDNA and other biomass.
