Continuous antimicrobial susceptibility testing in drug discovery

Abstract

High throughput screening of potential antimicrobial compounds generally involves an optically-based measurement, at regular time intervals, of a parameter such as absorbance that is proportional to bacterial growth. In practice such an approach requires repeated removal of microplates from the incubator. The reliability of results in such a system can however be seriously compromised by factors such as temperature fluctuations and evaporation from microplate wells. This article describes a system that incorporates in a single instrument a spectrometer, spectrofluorometer, incubator, shaker and microplate lid heater, thus overcoming the technical shortcomings of the standard approach, and enabling problem-free evaluation of antimicrobial compounds.

Antimicrobial susceptibility testing (AST) is an essential technique in many different disciplines, from pathology through to drug development. In the pathology setting, AST is used to determine the resistance of a bacterial strain to a host of antimicrobials, and is therefore a frontline tool in the control of nosocomial infections such as methicillin resistant Staphylococcus aureus (MRSA). In the research setting the test is used slightly differently to determine the efficacy of novel antimicrobials against a number of different bacterial species. At the University of Helsinki's Viikki Drug Discovery Technology Centre, an advanced approach to AST is being used to examine the efficacy of potential antimicrobials from biological extracts.