BioCentury
ARTICLE | Distillery Therapeutics

Infectious disease

April 17, 2018 9:10 PM UTC

Cell culture and mouse studies identified an odilorhabdin-based bacterial ribosomal 30S subunit inhibitor that could help treat bacterial sepsis and other bacterial infections. Screening of small molecules derived from 80 strains of the nematode symbiont Xenorhabdus, testing in bacterial growth assays and optimization of the top hit yielded an odilorhabdin-based compound that inhibited the growth of Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Enterobacter aerogenes, Proteus mirabilis, Staphylococcus aureus and Enterococcus faecalis, with minimum inhibitory concentration (MIC) values of 4-16 µg/mL, and crystallographic analysis showed the compound bound the decoding center of the bacterial ribosomal 30S subunit. In a mouse model of K. pneumoniae-induced sepsis, the compound decreased bacterial colony forming units (CFUs) in the blood compared with no treatment. In a mouse model of K. pneumoniae lung infection, the compound decreased bacterial CFUs in the lung. Next steps by Nosopharm S.A.S. include IND-enabling studies of NOSO-502, an optimized version of the compound. ...