Project description:Antibiotic resistance associated with the expression of the clinically significant carbapenemases, IMP, KPC, and NDM and OXA-48 in Enterobacteriaceae is emerging as a worldwide calamity to health care. In Australia, IMP-producing Enterobacteriaceae is the most prevalent carbapenemase-producing Enterobacteriaceae (CPE). Genomic characteristics of such carbapenemase-producing Enterobacteriaceae (CPE) are well described, but the corresponding proteome is poorly characterised. We have thus developed a method to analyse dynamic changes in the proteome of CPE under antibiotic pressure. Specifically, we have investigated the effect of meropenem at sub-lethal concentrations to develop a better understanding of how antibiotic pressure leads to resistance. Escherichia coli, producing either NDM, IMP or KPC type carbapenemase were included in this study, and their proteomes were analysed in growth conditions with or without meropenem.
Project description:Understand the mechanisms of evolution in large-scale bio-production by tracking population dynamics leading to production decline in mevalonic acid-producing Escherichia coli. Industrial bioproduction entails growth of the production host to large bioreactors (e.g. 1-300 m3). This may put the organism at risk for generating non-producing subpopulations of genetic heterogeneity, which is not phenotypically detected at lab-scale (e.g. 2 L). To study these dynamics, we experimentally simulated these growth durations by passing mevalonic acid-producing E. coli to maintain the populations in exponential growth for 45 generations.
