The effect of antibiotic resistance on bacterial cell maintenance In gram-negative bacteria

Antibiotic resistance has become a global concern, yet many of the mechanisms involved in antibiotic resistance remain poorly understood. Methods of antibiotic resistance are as diverse as antibiotics themselves, ranging from pump-driven mechanisms to eliminate a drug to host repair strategies to mitigate drug-induced damage. The research included in this thesis investigates the characteristics of two forms of antibiotic resistance found in bacteria: response to DNA-intercalators and efflux pumps. We demonstrate in vivo and in vitro that Ecm16 can render resistance against the DNA-intercalator echinomycin. Ecm16 belongs to a sub-class of UvrA-like proteins that are still poorly characterized. This work shows that, like UvrA, Ecm16 functionality requires two ATP-binding sites. Our collaborators have solved its crystal structure allowing a more in-depth assessment of its variation from other UvrA proteins. The second project focuses on physiological changes associated with the antibiotic efflux pump AcrAB-TolC. Although multi-drug efflux has been fairly well characterized, its consequences on cell fitness and development are still largely a mystery. My preliminary data revealed morphological changes in acrAB-tolC overexpression mutants in the presence of lignin-derived vanillate. Although recent research has hinted towards a connection between overexpression of AcrAB-TolC with changes in cell shape, this connection is still undefined. Collectively, the work presented in this thesis provide new insights to the various strategies that bacteria use to become antibiotic resistant.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Erlandson, Amanda Lee

Contributors dc:contributor

• Mera, Paola E
• Blanke, Steven
• Vanderpool, Carin
• Slauch, James

• Antibiotic Resistance
• Cellular Maintenance
• Cell Shape

Statement dc:rights

• Copyright 2023, Amanda Erlandson

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/120568

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F120568