Forging new antibiotic combinations under iron-limiting conditions.

Forging new antibiotic combinations under iron-limiting conditions.
Antimicrob Agents Chemother. 2020 Jan 06;:
Authors: Chan DCK, Guo I, Burrows LL
Abstract
Pseudomonas aeruginosa is a multidrug-resistant nosocomial pathogen. We showed previously that thiostrepton (TS), a gram-positive thiopeptide antibiotic, was imported via pyoverdine receptors and synergized with iron chelator deferasirox (DSX) to inhibit the growth of P. aeruginosa and Acinetobacter baumannii clinical isolates. A small number of P. aeruginosa and A. baumannii isolates were resistant to the combination, prompting us to search for other compounds that could synergize with TS against those strains. From literature surveys we selected 14 compounds reported to have iron-chelating activity, plus one iron analogue, and tested them for synergy with TS. Doxycycline (DOXY), ciclopirox olamine (CO), tropolone (TRO), clioquinol (CLI), and gallium nitrate (GN) synergized with TS. Individual compounds were bacteriostatic but the combinations were bactericidal. Our spectrophotometric data and chrome azurol S agar assay confirmed that the chelators potentate TS activity through iron sequestration rather than through their innate antimicrobial activities. A triple combination of TS + DSX + DOXY had the most potent activity against P. aeruginosa and A. baumannii isolates. One P. aeruginosa clinical isolate was resistant to the triple combination, but susceptible to a triple combin...

Source: Antimicrobial Agents and Chemotherapy - January 5, 2020 Category: Microbiology Authors: Chan DCK, Guo I, Burrows LL Tags: Antimicrob Agents Chemother Source Type: research