(387m) Metabolic Insights into Aminoglycoside Tolerance in Escherichia coli: Implications for Process Development and Pharmaceutical Innovation

Persistent bacterial contamination and infections pose significant challenges to pharmaceutical manufacturing and healthcare, contributing to treatment failures, increased production costs, and operational risks - even in the absence of genetic antibiotic resistance. My research investigates the metabolic basis of antibiotic tolerance in both laboratory and uropathogenic Escherichia coli (UPEC) strains, with potential implications for improving process robustness and developing new therapeutic strategies.

We explored the role of aspartase (AspA), an enzyme central to aspartic acid metabolism, in bacterial persistence against aminoglycoside antibiotics. Genome-wide screening using a GFP-based promoter library revealed that exposure to gentamicin resulted in reduced expression of aspA. Deletion of aspA significantly increased tolerance to multiple aminoglycosides, suggesting a link between aspartate metabolism and bacterial survival under drug stress.

Proteomic analyses showed upregulation of pathways linked to ribosomal processes, and reporter assays confirmed increased activity of the rrnC operon, encoding ribosomal RNA components essential for protein synthesis. This indicates that metabolic disruptions from aspA loss may enhance ribosomal biogenesis, contributing to persistence phenotypes.

These insights could inform process development and manufacturing strategies by identifying metabolic vulnerabilities that might be exploited to reduce microbial persistence, improve bioprocess yields, and enhance product quality in pharmaceutical and biotechnological applications.

Research Interests:
I am broadly interested in molecular microbiology, microbial physiology, metabolic engineering, and the application of omics technologies to improve bioprocess development, product quality, and manufacturing efficiency in chemicals and pharmaceuticals. My technical skills include molecular biology techniques, bacterial genetics, fluorescence-based assays, proteomics, and data analysis. I am eager to contribute to innovative projects in process and product development across diverse sectors within the life sciences and chemical industries.