Enhancing Pseudomonas Aeruginosa Susceptibility to Antibiotics by Disrupting the Biofilms with Therapeutic Enzymes
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Abstract
Healthcare-acquired infections are common in medicine because they are often developed during hospitalization and cause rapid increase in mortality and morbidity rates. These infections are difficult to treat because many pathogens that cause them form antibiotic-resistant bacterial communities known as biofilms. Pseudomonas aeruginosa is an opportunistic bacterium that causes ventilator-associated pneumonia by forming biofilms in ventilators. Unfortunately, clinical observations and experimental studies have shown that antibiotics alone are frequently insufficient to eliminate biofilm infections. The goal of this research is to target specific components of the P. aeruginosa biofilm matrix. I plan to degrade these components to disrupt the biofilm structure. With the biofilm structure destroyed, the bacteria then become susceptible to antibiotics. To remove the bacterial biofilms grown in vitro, major biofilm constituents such as alginate and extracellular DNA were targeted with alginate lyase and DNase I. Simultaneously the antibiotics levofloxacin, ciprofloxacin, and tobramycin were added to kill the bacteria. As a result, treating P. aeruginosa biofilms with the enzymes and the antibiotics was effective in reducing biofilm biomass. However, there was no statistically significant difference between the enzymatic treatments. In future studies, the enzymes should be used alone as a control to ensure that they are active against P.aeruginosa biofilms. I conclude that effective treatment of biofilm infections requires a well-established strategy including the disruption of bacterial biofilms with the therapeutic enzyme alginate lyase and the selection of biofilm-active and well-penetrating antibiotics to kill the bacteria. Considering this research, my recommendation for the future is to investigate how to administer these treatments to patients in vivo.