Authors

Hana Ali

Document Type

Honors Thesis

Abstract

Antimicrobial resistance is a rapidly increasing threat to public health, where pathogens are no longer susceptible to antimicrobials prescribed to fight infections. Carbapenems are last-resort antimicrobials that bind penicillin-binding proteins (PBPs) and inhibit cell wall biogenesis, leading to death. Specifically, the pathogen Acinetobacter baumannii (Ab) demonstrated carbapenem tolerance, or the ability of bacteria to survive in the toxic concentrations without changing the minimal inhibitory concentration. These data represent the first study to understand carbapenem tolerance in Ab. Here, we investigated the physiological significance of low molecular weight (LMW) PBPs, which have not been extensively studied in bacteria and could represent a promising target for antimicrobial therapy. To understand factors that mediate carbapenem tolerant Ab, we engineered LMW PBP genetic mutations, imaged the cellular morphologies and tested meropenem susceptibility in the mutant strains. Our data suggest that molecular mechanisms regulate LMW PBP activity in response to cell wall damage.

Publication Date

12-1-2020

Language

English

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