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Forging New Antibiotic Combinations under Iron-Limiting Conditions
Ist Teil von
Antimicrobial agents and chemotherapy, 2020-02, Vol.64 (3)
Ort / Verlag
United States: American Society for Microbiology
Erscheinungsjahr
2020
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
is a multidrug-resistant nosocomial pathogen. We showed previously that thiostrepton (TS), a Gram-positive thiopeptide antibiotic, is imported via pyoverdine receptors and synergizes with iron chelator deferasirox (DSX) to inhibit the growth of
and
clinical isolates. A small number of
and
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 potentiate TS activity through iron sequestration rather than through their innate antimicrobial activities. A triple combination of TS plus DSX plus DOXY had the most potent activity against
and
isolates. One
clinical isolate was resistant to the triple combination but susceptible to a triple combination containing higher concentrations of CLI, CO, or DOXY. All
isolates were susceptible to the triple combinations. Our data reveal a diverse set of compounds with dual activity as antibacterial agents and TS adjuvants, allowing combinations to be tailored for resistant clinical isolates.