HALO384: a halo-based potency prediction algorithm for high-throughput detection of antimicrobial agents.
A high-throughput (HT) agar-based halo assay is described, which allows for rapid screening of chemical libraries for bioactivity in microorganisms such as yeast and bacteria. A pattern recognition algorithm was developed to identify halo-like shapes in plate reader optical density (OD) measurements. The authors find that the total growth inhibition within a detected halo provides an accurate estimate of a compound's potency measured in terms of its EC(50). The new halo recognition method performs significantly better than an earlier method based on single-point OD readings. An assay based on the halo algorithm was used to screen a 21,120-member library of drug-like compounds in Saccharomyces cerevisiae, leading to the identification of novel bioactive scaffolds containing derivatives of varying potencies. The authors also show that the HT halo assay can be performed with the pathogenic bacterium Vibrio cholerae and that liquid culture EC(50) values and halo scores show a good correlation in this organism. These results suggest that the HT halo assay provides a rapid and inexpensive way to screen for bioactivity in multiple microorganisms.
Woehrmann
Marcos H
MH
Department of Biomolecular Engineering, UC Santa Cruz, Santa Cruz, California, USA.
Gassner
Nadine C
NC
Bray
Walter M
WM
Stuart
Joshua M
JM
Lokey
Scott
S
D000465:Algorithms; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D001681:Biological Assay; D003470:Culture Media; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D054852:Small Molecule Libraries; D013997:Time Factors; D014734:Vibrio cholerae / Q000187:drug effects
D000890:Anti-Infective Agents; D000935:Antifungal Agents; D003470:Culture Media; D054852:Small Molecule Libraries