Chloe Ghent

UC San Francisco

“Expanding Our Understanding of Bacterial Antibiotic Resistance Mechanisms Through Evaluation of Antibiotic-Induced Resistance Gene Regulation”

Antibiotic resistance among bacterial strains is currently on the rise, which poses a substantial public health threat. This necessitates a better understanding of antibiotic resistance mechanisms to engineer future antibiotic classes that can circumvent these pathways. Many antibiotics operate by binding to the bacterial ribosome and disrupting protein translation; subsequently, many resistance genes modify the bacterial ribosome to occlude antibiotic binding. The expression of antibiotic resistance genes is often induced by the presence of the antibiotic that the gene confers resistance to; this can be achieved through a regulation mechanism that involves an upstream open reading frame (uORF) that precedes the antibiotic gene sequence. I am interested in characterizing the expression of the antibiotic resistance gene cfr, which encodes a protein that methylates the bacterial ribosome and inhibits antibiotic binding. I hypothesize that cfr regulation is facilitated by a conserved uORF that precedes the gene. I am proposing that regulation occurs at both the translational and protein activity level and is sensitized to the presence of antibiotic.


I am proposing to investigate the regulation of the bacterial antibiotic resistance gene, cfr, via an upstream open reading frame. I hypothesize that regulation is occurring at both the translational and protein activity level and plan to test my hypothesized models using biochemistry and microbiology techniques. I aim to further understand how cfr expression is sensitized to the presence of antibiotics to help inform antibiotic engineering that circumvents resistance mechanisms.

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