Rosmarinic Acid and Sodium Citrate Have a Synergistic Bacteriostatic Effect against Species by Inhibiting Iron Uptake.

Background: New strategies are needed to combat multidrug-resistant bacteria. The restriction of iron uptake by bacteria is a promising way to inhibit their growth. We aimed to suppress the growth of bacterial species by inhibiting their ferric ion-binding protein (FbpA) using food components.

Methods: Twenty spices were selected for the screening of FbpA inhibitors. The candidate was applied to antibacterial tests, and the mechanism was further studied.

Results: An active compound, rosmarinic acid (RA), was screened out. RA binds competitively and more tightly than Fe to VmFbpA, the FbpA from , with apparent values of 8 μM vs. 17 μM. Moreover, RA can inhibit the growth of to one-third of the control at 1000 μM. Interestingly, sodium citrate (SC) enhances the growth inhibition effect of RA, although SC only does not inhibit the growth. The combination of RA/SC completely inhibits the growth of not only at 100/100 μM but also the vibriosis-causative pathogens and , at 100/100 and 1000/100 μM, respectively. However, RA/SC does not affect the growth of .

Conclusions: RA/SC is a potential bacteriostatic agent against species while causing little damage to indigenous gastrointestinal bacteria.