Functional Proteomics Analysis of Norfloxacin-Resistant Edwardsiella tarda

Multidrug-resistant Edwardsiella tarda threatens both sustainable aquaculture and human health, but the
control measure is still lacking. In this study, we adopted functional
proteomics to investigate the molecular mechanism underlying norfloxacin
(NOR) resistance in E. tarda. We found
that E. tarda had a global proteomic
shift upon acquisition of NOR resistance, featured with increased
expression of siderophore biosynthesis and Fe3+-hydroxamate
transport. Thus, either inhibition of siderophore biosynthesis with
salicyl-AMS or treatment with another antibiotic, kitasamycin (Kit),
which was uptake through Fe3+-hydroxamate transport, enhanced
NOR killing of NOR-resistant E. tarda both in vivo and in vitro. Moreover,
the combination of NOR, salicyl-AMS, and Kit had the highest efficacy
in promoting the killing effects of NOR than any drug alone. Such
synergistic effect not only confirmed in vitro and in vivo bacterial killing assays but also applicable to
other clinic E. tarda isolates. Thus,
our data suggest a proteomic-based approach to identify potential
targets to enhance antibiotic killing and propose an alternative way
to control infection of multidrug-resistant E. tarda.