Evaluating LC–MS/MS To Measure Accumulation of Compounds within Bacteria

• DOI: 10.1021/acsinfecdis.8b00083
• Publication Date: 2018-06-30T16:28:28Z
• Authors: Ramkumar Iyer; Zhengqi Ye; Annette Ferrari; Leonard Duncan; M. Angela Tanudra; Hong Tsao; Tiansheng Wang; Hong Gao; Christopher L. Br...; Alice L. Erwin
• Keywords: Efflux

A general method for determining bacterial uptake of compounds independent antibacterial activity would be a valuable tool in drug discovery. LC-MS/MS assays have been described, but it has not shown whether the data can used directly to inform medicinal chemistry. We describe evaluation an assay measuring association with bacteria, using set over hundred (inhibitors NAD-dependent DNA ligase, LigA) which vitro potency and had determined. All were active against efflux-deficient strain Escherichia coli reduced LigA (E. ligA251 ΔtolC). Testing single compound concentration incubation time, we found that, equipotent compounds, values predictive activity. This indicates that measured bacteria-associated was necessarily exposed target enzyme. Our suggest while exclusion from bacteria is major reason poor potent distribution within cell may also problem. The relative importance these factors likely vary one chemical series another. observations provide directions further study this difficult issue.