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The Effect of Novel Biofilm Inhibitors on Antibiotic Resistance in E. coli

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[Technical Report, Annual Report]

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E. coli is a prevalent multi-drug resistant MDR pathogen associated with trauma-related injuries of military personnel. Biofilm formation is associated with many of these MDR strains of E. coli. Curli, the first identified functional amyloid, are the major proteinaceous component of E.coli biofilms and they are implicated in cell attachment, virulence, and providing structural stability to biofilms. The amyloid biogenesis system in E. coli is remarkably adept in its ability to restrict amyloid formation to the cell surface. Through rapid polymerization and dedicated secretion machinery, these bacteria have evolved to generate large quantities of biofilm amyloid fibril scaffolding while minimizing the risks of self-toxicity through accumulation of intracellular aggregates. The protein CsgA is the dominant protein in these amyloid fibrils. We hypothesize that populations of transient -sheet oligomers, composed of CsgA, exist within Gram negative biofilms, and that these structures can serve as targets for designed -sheet peptides to suppress fibril formation in the EM. In turn, suppression of biofilm formation should improve antibiotic penetrance and reduce resistance.

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  • Medicine and Medical Research
  • Microbiology

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[A, Approved For Public Release]