Intracellular penetration of novel antimicrobials in human THP-1 Macrophages infected with Listeria Monocytogenes

Abstract

Antimicrobial resistance is increasing world-wide and there is a need for new, more effective drug treatments. Intracellular bacterial infections are among the most deadly and difficult to treat. Members of the Mycobacterium tuberculosis complex infect intracellularly and are one of the top ten causes of death worldwide. Novel stilbenoid compounds have been identified that kill M tuberculosis in vitro. Human macrophage cells were infected with Listeria monocytogenes, a safer intracellular pathogen to work with, and treated for five hours with selected compounds at various concentrations. Three L. mo.nocytogenes strains were used in order to determine if the location of the bacteria within the cell had an impact on drug activity or not. Tue wild-type and ActA-negative strains, which escape the initial phagosome and reside in the cytosol of the macrophage, were killed within the five holll'. window; however, the strain that could not escape the phagosome, DP-L2319, was not significantly reduced. While investigating the intracellular efficacy of the selected compounds, it was observed that compound SK-03- 92 caused morphological changes and detachment of the macrophage cells from the � tissue culture plate. It appears t~e drug caused some form of programmed cell death, although which pathway remains to be further clarified.