Survival Mechanisms Triggered in Escherichia coli by HVAC-Aerosolization Induced Stress- A Molecular Dynamics Study

LEILY KHALEGHI, Texas A&M University

     Abstract Number: 419
     Working Group: Bioaerosols

Abstract
Indoor airborne pathogens increasingly display antimicrobial resistance (AMR) genes, with the most diverse and equitable antimicrobial-resistant populations found in hospitals. According to recent studies, indoor environmental factors, particularly airflow pressure, trigger stress response genes that incidentally support AMR behavior. Membrane-bound proteins are believed to activate as a survival mechanism to pressure caused by aerosolization, particularly the efflux pump and mechanosensitive channel proteins. The goal of this study was to visualize the specific molecular mechanisms employed by the small mechanosensitive channel to guard the cell against aerosolization stress and investigate how these mechanisms interact with common antibiotics to induce antibiotic resistance or susceptibility. This was done using the Schrodinger platforms Wizard, Glide, SiteMap, and Desmond. Molecular docking of the antibiotics Ampicillin, Gentamycin, Kanamycin, Sulfamethoxazole-Trimethoprim, and Chloramphenicol to the protein structure yielded Glide Docking Scores, measuring the strength of the binding event. Molecular dynamics simulations were conducted for the protein, protein-antibiotic complex, and protein-antibiotic (unbounded) environment. For each of the three scenarios, two molecular dynamics simulations were performed: one at 300 K and 1.01325 bar pressure and one at 300 K and 1.150112 bar pressure. From these simulations, Simulation Interactions Diagrams were produced to determine the simulation’s stability, as well as the protein’s flexibility. Additionally, plots of the channel’s opening width vs. time were collected from the simulation data. For both the bound and unbound environments, the channel’s openings widen at high pressure, and the overall width of the Carboxy-Terminal Domains increases. The data indicates that it is the pressure change that primarily affects channel activity, with the simulations visualizing the opening mechanism of the protein.