The Polyaminoisoprenyl Potentiator NV716 Revives Old Disused Antibiotics against Intracellular Forms of Infection by Pseudomonas aeruginosa.

ABSTRACT: Active efflux confers intrinsic resistance to multiple antibiotics in Pseudomonas aeruginosa, including old disused molecules. Beside resistance, intracellular survival is another reason for failure to eradicate bacteria with antibiotics. We evaluated the capacity of polyaminoisoprenyl potentiators (designed as efflux pump inhibitors [EPIs]) NV716 and NV731 compared to PAβN to restore the activity of disused antibiotics (doxycycline, chloramphenicol [substrates for efflux], and rifampin [nonsubstrate]) in comparison with ciprofloxacin against intracellular P. aeruginosa (strains with variable efflux levels) in THP-1 monocytes exposed over 24 h to antibiotics alone (0.003 to 100× MIC) or combined with EPIs. Pharmacodynamic parameters (apparent static concentrations [Cs] and maximal relative

SUBMITTER: Wang G 

PROVIDER: S-EPMC8092510 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature