Testing antibacterial drugs against nongrowing bacteria

Abstract

All antibiotics currently in use were discovered due to their ability to stop bacterial growth. However, only a few of them can kill nongrowing bacteria. During chronic and recurrent infections, a large fraction of the pathogenic bacteria is nongrowing or grow very slowly. Drugs are needed that kill nongrowing bacteria and it is therefore reasonable to look for potential candidates in already existing drug libraries. We treated non-growing stationary phase cultures with the drug candidates looking for those that cause post-incubation regrowth delay. A colony counting method optimized for high throughput was used to determine the bactericidal activity of the hit compounds. 38 drugs were previously identified to increase regrowth delay of nongrowing E. coli. They were further tested for their activity against nongrowing Pseudomonas aeruginosa and Staphylococcus aureus. Several drugs of multiple classes – fluoroquinolones, macrolides, and anticancer drugs – were found to heavily increase the regrowth time of P. aeruginosa. Additionally, these drugs exhibited strong bactericidal effect, killing multiple magnitudes of bacteria. Fewer drugs were as effective against S. aureus, but a couple – an antiseptic/disinfectant and an anticancer drug - were found to increase the regrowth delay significantly and showed bactericidal activity.