Profiling susceptibility of NIAID Category A and B priority and emerging pathogens to define strain panels for drug discovery and active drug classes

Abstract

Drug susceptibility profiles of NIAID Category A and B priority and emerging pathogens to standard of care drugs were assessed to determine susceptibility against clinical strains in addition to reference laboratory strains to establish a comparison resource for the performance of drug candidates, to define non-redundant minimal strain panels for individual species and the group of species for use in drug screening programs, and provide pharmacophore classification. Profiling of standard of care drugs against strains of each species revealed a broad spectrum of susceptibility among strains in each species with important differences between standard laboratory reference strains and strains sof clinical origin. Unbiased hierarchical clustering analyses of strain susceptibilities within each species group and strains from all the species identified subsets of non-redundant strains that are able to classify the susceptibility range for each species and able to classify all the species. This analysis established a reduced targeted set of Category A and B priority pathogen strains for testing the potency of drug candidates against each species and pan-species. This approach also discriminated pharmacophore classification for each species. This information can be applied to directed screening efforts to guide the selection of drug classes for derivatization and repurposing, and advance drug candidates with the greatest potential for efficacy against NIAID Category A and B priority and emerging pathogens.