Karan Hooda

Introduction. Cystic Fibrosis (CF) is a genetic disorder in which there is a deletion of F508 in the cystic fibrosis transmembrane conductance regulator gene (CFTR).¹ This leads to mucus buildup and dehydration of respiratory airway surfaces, providing the optimal environment for pathogens to inhabit.² Pseudomonas aeruginosa is a bacterium that thrives in moist environments and is able to colonize medical devices, making it one of the primary causes of nosocomial infections.² Upon infection, P. aeruginosa utilizes the Quorum Sensing (QS) intercellular signaling pathway to upregulate the production of virulence factors, biofilm formation, and antibiotic-resistance.^1,5 Current treatments like broad spectrum antibiotics are ineffective due to multi-drug resistant mechanisms while causing side effects.¹ Therefore, new approaches have focused on disrupting the Las and Rhll components of the QS signaling pathway in order to prevent biofilm formation.¹ These include FABHL and CABHL, two QS signaling molecule mimics, and Psychrobacter spp. TAE2020’s supernatant, which has shown to have anti-virulence factor properties.^3,4 Methods. FABHL and CABHL were tested in biofilm assays against 2 multi-drug resistant strains of P. aeruginosa in addition to human peripheral blood mononuclear cells (PBMCs). Following this, analysis of Las and Rhll gene expression was determined via qRT-PCR.³ Likewise, the cell-free supernatant of TAE2020 was tested in biofilm and virulence factor assays against 5 P. aeruginosa isolates collected from CF patients.⁴ Two experiments were conducted: one at 0 hours and one at 24 hours of mature biofilm development. Results. FABHL and CABHL were able to reduce both las and Rhll gene expression levels by 50%; however, these compounds also yielded a PBMC viability of 49.2% and 57.4%, respectively.³ 50%-90% biofilm reduction was observed in the 0 hour experiment by the supernatant; however, there was minimal reduction in the 24 hour mature biofilm assay. TAE2020 displayed the ability to disrupt virulence factor production as pyocyanin was reduced in 4 of the 5 strains while protease was reduced in 3 of the 5 strains.⁴ Conclusion. Pseudomonas aeruginosa is an opportunistic bacterium that causes nosocomial infections, particularly in immunocompromised individuals. Multi-drug resistant mechanisms of the bacteria has led to the development of new approaches like FABHL/CABHL and TAE2020 supernatant as a means to prevent biofilm formation. While these compounds show promise in reducing biofilm production in vitro, additional modifications and studies need to be conducted to reduce harmful side effects before moving on to animal models and clinical trials.^3,4

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