Amonabactins
are a group of four related catecholate siderophores
produced by several species of the genus Aeromonas, including A. hydrophila and the fish pathogen A. salmonicida subsp. salmonicida. Although
the gene cluster encoding amonabactin biosynthesis also contains a
gene that could encode the ferri-siderophore receptor (fstC), to date there is no experimental evidence to explain its role.
In this work, we report the identification of the amonabactins’
outer membrane receptor and the determination of the minimal structural
parts of these siderophores involved in the molecular recognition
by their cognate receptor. The four natural amonabactin forms (P750,
T789, P693, and T732) and some mono and biscatecholate amonabactin
analogues were chemically synthesized, and their siderophore activity
on A. salmonicida FstC(+) and FstC(−) strains
was evaluated. The results showed that each amonabactin form has quite
different growth promotion activity, with P750 and T789 the most active.
The outer membrane receptor FstC recognizes more efficiently biscatecholate
siderophores in which the length of the linker between the two iron-binding
catecholamide units is 15 atoms (P750 and T789) instead of 12 atoms
(P693 and T732). Analysis of the siderophore activity of synthetic
analogues indicated that the presence of Phe or Trp residues is not
required for siderophore recognition. The results together point toward
evidence that the amonabactin receptor FstC admits a high degree of
ligand plasticity. We also showed that FstC is present in most Aeromonas species, including relevant human and animal pathogens
as A. hydrophila. From the results obtained, we concluded
that the ferri-amonabactin uptake pathway involving the outer membrane
transporter FstC possesses a considerable functional plasticity that
could be exploited for delivery of antimicrobial compounds into the
cell. This would allow the use of the siderophore-based iron uptake
mechanisms to combat infections caused by species of the genus Aeromonas.
Aeromonas salmonicida subsp. salmonicida (A. salmonicida), a Gram-negative bacterium causing furunculosis in fish, produces the siderophores acinetobactin and amonabactins in order to extract iron from its hosts. While the synthesis and transport of both systems is well understood, the regulation pathways and conditions necessary for the production of each one of these siderophores are not clear. The acinetobactin gene cluster carries a gene (asbI) encoding a putative sigma factor belonging to group 4 σ factors, or, the ExtraCytoplasmic Function (ECF) group. By generating a null asbI mutant, we demonstrate that AsbI is a key regulator that controls acinetobactin acquisition in A. salmonicida, since it directly regulates the expression of the outer membrane transporter gene and other genes necessary for Fe-acinetobactin transport. Furthermore, AsbI regulatory functions are interconnected with other iron-dependent regulators, such as the Fur protein, as well as with other sigma factors in a complex regulatory network.
Bismuth is a heavy metal with antibacterial properties that has a long history of medicinal use. The results reported here suggest that bismuth(III) (chelated with deferiprone) could be used in aquaculture systems to treat bacterial disease outbreaks, greatly reducing antibiotic use. We tested bismuth susceptibility in a collection of aquaculture bacterial pathogens. In the presence of bismuth concentrations ranging from 1.3 to 13 µM, most bacteria started showing a drastic decrease in their growth ability, although with high inter- and intraspecific variability. The minimal inhibitory concentrations of bismuth ranged from 13 to more than 780 µM, depending on bacterial species and strain. The results of in vivo assays suggest that low concentrations of bismuth could be especially effective to treat vibriosis caused by Vibrio anguillarum, since bismuth greatly reduced mortality in experimentally infected fish without any observable side effects. A bismuth therapy, alone or combined with other antimicrobials, could contribute to reduce the use of antibiotics in aquaculture.
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