EPM35 (Efflux pump modulator 35) is a small molecule that bind AcrB (KD=0.29 uM), inhibit AcrAB-TolC and modulates bacterial efflux pump activity, reduces bacterial intracellular load.
EPM35 disrupts the growth of a Gram-negative human pathogen, Salmonella enterica serotype Typhimurium (S. Typhimurium), in macrophages.
EPM35 shows little effect on bacterial growth in standard microbiological media.
EPM35 prevents energy-dependent efflux pump activity in Salmonella and bound the AcrB subunit of the AcrAB-TolC efflux system with KDs in the micromolar range.
EPM35 could disrupt infection by specifically interfering with the export of bacterial toxic metabolites, host defense factors, and/or antibiotics.
EPM35 display antibacterial synergy with antimicrobial peptides, a class of host innate immune defense molecules present in body fluids and cells.
EPM35 also has synergistic activity with antibiotics exported by AcrAB-TolC in broth and in macrophages and inhibits efflux pump activity in MDR Gram-negative ESKAPE clinical isolates.