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Leveraging the ΦX174 Protein Antibiotic to Study MraY Structure, Function, and Regulation


Orta, Anna Karen (2024) Leveraging the ΦX174 Protein Antibiotic to Study MraY Structure, Function, and Regulation. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/ggr0-0n72.


The overuse of antibiotics has escalated the prevalence of bacterial resistance to existing treatments, posing a significant threat to global health. This rise in antimicrobial resistance (AMR) has spurred research into innovative therapeutic approaches. Among the most promising strategies is the use of viruses of bacteria for 'phage therapy'. This thesis delves into the interplay between antibacterial resistance and peptidoglycan biosynthesis, highlighting the pivotal role of the membrane protein MraY. We present the first structure of MraY from a pathogenic species, revealing its inhibition by the lysis protein from the bacteriophage ΦX174, protein E. Additionally, we analyze lipidic interactions with MraY, proposing a previously unexplored allosteric feedback mechanism for regulating its enzymatic activity. Building on these insights, we expand the application of protein E to non-native hosts, offering new avenues for the development of targeted antibiotic interventions. This work not only advances our understanding of the structural and functional dynamics of MraY but also paves the way for novel antibacterial strategies.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Phage therapy, antimicrobial proteins, cell lysis, protein E, MraY, SlyD, YES complex, peptidoglycan biosynthesis, bacterial cell wall inhibition, cryo-electron microscopy, bacteriophage, single-gene lysis
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Biochemistry and Molecular Biophysics
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Clemons, William M.
Thesis Committee:
  • Voorhees, Rebecca M. (chair)
  • Newman, Dianne K.
  • Bjorkman, Pamela J.
  • Clemons, William M.
Defense Date:20 May 2024
Funding AgencyGrant Number
NIHR01 GM114611
G. Harold and Leila Y. Mathers Foundationto Bil Clemons
Record Number:CaltechTHESIS:06042024-022255958
Persistent URL:
Related URLs:
URLURL TypeDescription for Ch. 3 for Ch. 2 and Ch. 3
Orta, Anna Karen0000-0002-8526-0383
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:16499
Deposited By: Anna Orta
Deposited On:06 Jun 2024 22:11
Last Modified:14 Jun 2024 21:21

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