High-throughput screening of a diversity collection using biodefense category A and B priority pathogens.
One of the objectives of the National Institutes of Allergy and Infectious Diseases (NIAID) Biodefense Program is to identify or develop broad-spectrum antimicrobials for use against bioterrorism pathogens and emerging infectious agents. As a part of that program, our institution has screened the 10 000-compound MyriaScreen Diversity Collection of high-purity druglike compounds against three NIAID category A and one category B priority pathogens in an effort to identify potential compound classes for further drug development. The effective use of a Clinical and Laboratory Standards Institute-based high-throughput screening (HTS) 96-well-based format allowed for the identification of 49 compounds that had in vitro activity against all four pathogens with minimum inhibitory concentration values of ≤16 µg/mL. Adaptation of the HTS process was necessary to conduct the work in higher-level containment, in this case, biosafety level 3. Examination of chemical scaffolds shared by some of the 49 compounds and assessment of available chemical databases indicates that several may represent broad-spectrum antimicrobials whose activity is based on novel mechanisms of action.
Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA. bill.barrow@okstate.edu
Esther W
EW
Barrow
Patricia A
PA
Clinkenbeard
Rebecca A
RA
Duncan-Decocq
Rachel F
RF
Perteet
Kimberly D
KD
Hill
Philip C
PC
Bourne
Michelle W
MW
Valderas
Christina R
CR
Bourne
Nicole L
NL
Clarkson
Kenneth D
KD
Clinkenbeard
William W
WW
Barrow
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects*; D023482:Bioterrorism; D002003:Brucella abortus / Q000187:drug effects; D055808:Drug Discovery; D004926:Escherichia coli / Q000187:drug effects; D005604:Francisella tularensis / Q000187:drug effects; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008826:Microbial Sensitivity Tests; D054579:National Institute of Allergy and Infectious Diseases (U.S.); D013211:Staphylococcus aureus / Q000187:drug effects; D014481:United States; D015010:Yersinia pestis / Q000187:drug effects
D000900:Anti-Bacterial Agents