Combating bacterial biofilms: Functional characterization of the Vibrio fischeri biofilm regulatory protein SypE
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Date
2023-12-15
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Authors
Abhulimen, Ehime Noah
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East Carolina University
Abstract
Antibiotic resistance represents a notable and increasing threat to healthcare and its economics. Biofilms are directly associated with bacterial tolerance to antibiotics. These biofilms are tightly regulated communities of matrix-associated bacteria and are a major component of bacterial pathogenesis including drug tolerance. Approximately 80% of chronic and recurrent microbial infections within the human body are due to bacterial biofilms (Sharma et al., 2019). This makes it imperative to understand how biofilms are made. In this proposal, I begin to reveal the molecular mechanism of an unusual regulatory protein essential for controlling biofilm formation, SypE, from the model organism Vibrio fischeri. SypE regulates the synthesis of a component of the biofilm matrix necessary for host infection. Based on previous findings, SypE has atypical functions compared to well characterized homologs. My fundamental hypothesis is that understanding the function and mechanism of SypE can be used to control the production of the biofilm matrix. My hypothesis will be addressed through two specific aims: 1) probing the SypE’s function using biochemical and structural characterization studies, and 2) modeling the structure of SypE through artificial intelligence methodologies. The performed research is innovative because it focuses on a system that is crucial for biofilm formation and serves as a pioneer for an investigation that has only been previously explored using cellular and genetic approaches. SypE also resides in a critical and conserved signaling pathway that regulates host-relevant biofilms. Ultimately, the structure-function approach presented here will provide information to fill our knowledge gaps and answer key questions related to the molecular mechanisms of SypE. Learning how proteins like SypE function will ultimately allow us to develop ways to combat biofilm induced antimicrobial tolerance and reduce bacterial infections in hospital patients, medical devices, and healthcare workers.