Siderophore Production and its Role as Therapeutic Agent

Siderophores are iron chelators, which are produced by bacteria under iron-deficient conditions required for their growth. Therefore, siderophores can be used as a carrier to direct drugs into the bacteria and kill them. The present study was designed to screen siderophore production using different bacteria using an iron-deficient medium and its synergistic capability to kill drug-resistant bacteria. Siderophore under iron-deprived condition was evaluated by chrome azurol S (CAS) assay. Whereas, broth micro-dilution method and checkerboard assay were used to determine the antimicrobial properties of selected drugs or epigallocatechin gallate (EGCG) individually or in combination with synthetic siderophore. Results demonstrated that the entire tested microorganisms produced siderophore under the iron-deprived condition as evidenced by orange halo zones in CAS agar plates.  Gram-negative bacteria produced more siderophores as reflected by orange color with bacterial zone inhibition of 17-22mm as compared to Gram-positive bacteria (13-15mm). As compared to antibiotics and EGCG, acetohydroxamic acid (aHa; synthetic siderophore) showed no antibacterial properties (1500 - 6500 µg/ml). The synergism of aHa with tetracycline, ceftriaxone, and EGCG (FIC index <0.5) against S. typhi, methicillin-resistant and sensitive Staphylococcus aureus, and E. coli were evident. In conclusion, siderophore may be considered a potential candidate to design different combination therapy against emerging antimicrobial-resistant pathogens.