Abstract
Due to the global threat of rising antimicrobial resistance, novel antibiotics are urgently needed. We investigate natural products from Myxobacteria as aninnovative source of such new compounds. One bottleneck in the process is typically the elucidation of their mode-of-action. We recently established isothermal microcalorimetry as part of a routine profiling pipeline. This technology allows for investigating the effect of antibiotic exposure on the total bacterial metabolic response, including processes that are decoupled from biomass formation. Importantly, bacteriostatic and bactericidal effects are easily distinguishable without any user intervention during the measurements. However, isothermal microcalorimetry is a rather new approach and applying this method to different bacterial species usually requires pre-evaluation of suitable measurement conditions. There are some reference thermograms available of certain bacteria, greatly facilitating interpretation of results. As the pool of reference data is steadily growing, we expect the methodology to have increasing impact in the future and expect it to allow for in-depth fingerprint analyses enabling the differentiation of antibiotic classes.
Highlights
The aim of this method is to apply isothermal microcalorimetry species and provides information on the bactericidal or (IMC) as a medium throughput assay in mode-of-action bacteriostatic nature of the compound itself.(MoA) profiling of new antibacterial compounds
If there is a delay in time until a heat flow is detectable it means that the bacteria do not yet produce a heat signal above the detection limit
Isothermal microcalorimetry measures energy emitted from a specimen over time and this energy release is a result of all biological, physical andchemical processes
Summary
The aim of this method is to apply isothermal microcalorimetry species and provides information on the bactericidal or (IMC) as a medium throughput assay in mode-of-action bacteriostatic nature of the compound itself. The instrument provides further advantages over alternative methods for measuring bacterial growth kinetics, such as the standard turbidity method, which is based on the measurement of optical density at 600 nm (OD
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