Open AccessSpiropiperidyl rifabutins: expanded in vitro testing against ESKAPE pathogens and select bacterial biofilms
Author(s) -
MaríaPaz Cabal,
Timothy E. Long,
Edward Turos,
Ana-Belén Garcı́a,
Jessie L Allen,
Bridget G. Budny,
Lindsey N. Shaw
Publication year - 2020
Publication title -
journal of antibiotics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.56
H-Index - 80
eISSN - 1881-1469
pISSN - 0021-8820
DOI - 10.1038/s41429-020-0346-x
Subject(s) - enterococcus faecium , microbiology and biotechnology , staphylococcus aureus , in vitro , rifabutin , antimicrobial , chemistry , antibiotics , bacteria , vancomycin , rifamycin , enterococcus , biology , biochemistry , genetics , clarithromycin
The expanded microbiological evaluation of a series of rifastures, novel spiropiperidyl rifamycin derivatives, against clinically relevant ESKAPE bacteria has identified several analogs with promising in vitro bioactivities against antibiotic-resistant strains of Enterococcus faecium and Staphylococcus aureus. Thirteen of the rifastures displayed minimum inhibitory concentrations (MICs) below 1 µg/ml against the methicillin- and vancomycin-resistant forms of S. aureus and E. faecium (MRSA, VRSA, VRE). Aryl-substituted rifastures 1, 11, and 12 offered the greatest bioactivity, with MICs reaching ≤0.063 µg ml -1 for these human pathogens. Further analysis indicates that diphenyl rifasture 1 had greater antibiofilm activity against S. aureus and lower cytotoxicity in mammalian HEK cells than rifabutin.