The Metabolism of Uropathogenic Bacteria in in Vitro Human Urine Cultures
Date
2024-10-07
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Abstract
Urinary tract infections (UTIs) are common infections primarily caused by bacterial colonization of the host’s bladder and/or kidney. Research into the molecular underpinnings behind UTIs primarily focused on the various macromolecular virulence factors that enable uropathogens to invade and colonize the host’s urinary tract. As such, there is an extensive body of literature characterizing these UTI-associated virulence factors. However, one important aspect that remains relatively unexplored is pathogen metabolism. Pathogens must be able to metabolize the nutrients available in its microenvironment to survive and grow within their host. Human urine is a chemically complex medium with a diverse range of amino acids and nucleic acids, but generally lacks carbohydrates, the preferred carbon source for most microbes and thus, urine is often considered a nutrient-poor substance. Recent technological advancement in metabolomic tools can allow researchers to discover new insights into uropathogen metabolism and further our understanding of how uropathogens overcome nutritional adversity and survive in human urine. To address this gap, I used liquid chromatography-mass spectrometry (LC-MS) to analyze in vitro human urine cultures of uropathogenic bacteria. My initial metabolomics survey of eight common uropathogenic species found that these species can be divided into four distinct metabolic clades: serine consumers, glutamine consumers, amino acid abstainers, and amino acid minimalists. There were also several other metabolic phenotypes exclusive to a single or a few species. Metabolites found to be secreted by uropathogens could be candidate UTI biomarkers. Previous work discovered that agmatine was a robust UTI biomarker for several bacterial species in the Enterobacterales order including Escherichia coli. Investigation into bacterial agmatine production revealed that E. coli utilizes several different decarboxylase-based acid resistance systems in urine, induced at different pH ranges. Meanwhile, a few non-Enterobacterales species, like Staphylococcus spp., were found to secrete N6-methyladenine, which was also identified as a UTI biomarker. Advances to metabolomics methods can greatly enhance the efficiency of these metabolomics analyses, and so we developed a new LC-MS strategy for monitoring microbial metabolic activity in real-time. By investigating uropathogen metabolism with current metabolomics tools, we can better understand how these pathogens may persist and thrive during UTIs.
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Keywords
urinary tract infections, uropathogens, liquid chromatography-mass spectrometry, bacterial metabolism, metabolomics
Citation
Chan, C. C. Y. (2024). The metabolism of uropathogenic bacteria in in vitro human urine cultures (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.