BioCentury
ARTICLE | Distillery Therapeutics

Infectious disease

July 18, 2017 8:58 PM UTC

In vitro, moth, sheep blood sample and mouse studies identified inhibitors of Staphylococcus aureus flotillin that could help treat S. aureus infections. In a wax moth larva model of S. aureus infection, knockout of bacterial flotillin increased survival compared with normal expression. Screening of small molecules known to interact with cell membranes in bacterial cell-based oligomerization assays identified three compounds -- Impavido miltefosine, 5-doxyl-stearic acid and zaragozic acid -- as inhibitors of flotillin oligomerization, which is essential to the protein's activity. In sheep blood, supernatant from S. aureus cultures treated with any of the three compounds decreased blood cell lysis compared with supernatant from untreated S. aureus cultures. In a mouse model of S. aureus infection, flotillin knockout in bacteria or the three flotillin inhibitors increased survival compared with normal flotillin expression or no treatment. Next steps could including testing the flotillin inhibitors in additional models of S. aureus infections...