Tahsin Bari

Introduction: Cystic fibrosis (CF) is a disorder that affects the balance of ion transport and hydration inside the body causing viscous mucous secretions that accumulate in the body.¹ The disease is caused by inheritance of two mutant copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and has an incidence rate of 1/3400 live births in the caucasian population.² Infants are routinely screened at birth for CF with family history of CF and a positive sweat chloride test (sweat chloride > 60 mmol/L) sufficient for diagnosis.³ Patients typically present with chronic respiratory infections and symptoms of malabsorption.² Mainstays of treatment include antibiotics and airway clearance therapies, yet the primary cause of mortality in CF patient is still lung disease with a median age of survival ranging from 40-50 years. As the disease progresses, patients are more likely to have chronic lung infections caused by Psuedomonas aeruginosa which suppresses the host immune response and forms antibiotic resistant biofilms that are difficult for medications to penetrate through.⁴ Multidrug resistant pseudomonas infections is a significant issue for CF patients and recently there has been significant research towards novel treatments. To categorize the different novel treatments, a literature review was performed and targeted to find treatments that take advantage of the existing methods of immune defense in the body.  Methods: A literature search through Pubmed was performed. Search parameters included only articles published from 2018-2022 and keywords used for the search were “pseudomonas aeruginosa biofilm treatment”. Findings are described below.  Results: The in vitro study of let-7b-5p miRNA demonstrated how targeting essential biofilm proteins decreased formation of new biofilm, but was not effective in reducing existing biofilm.⁵ The peptide conjugated phosphorodiamidate oligomers (PPMOs) effectively traveled through existing biofilm to target mRNAs for essential biofilm proteins.⁶ The antimicrobial peptide Pseudin-2 and its analogs were found to significantly decrease wound size in mice with P. aeru infected wounds.⁷ The synthetic peptide SET-M33 was developed to resist degradation in biofilm fluids and was shown to effectively localize to the lungs to decrease the amount of biofilm formation.⁸  Conclusions: Biofilm targeting is likely to provide a new method to treat drug resistant P. aeru infections that current drugs are not able to treat. Future clinical studies regarding peptide based methods could be beneficial as these peptides have already demonstrated in vivo efficacy.

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