J Korean Med Sci.  2009 Apr;24(2):289-295. 10.3346/jkms.2009.24.2.289.

Effect of Iron-Chelator Deferiprone on the In Vitro Growth of Staphylococci

• Kim CM
• Shin SH

• KMID: 1779132
• DOI: http://doi.org/10.3346/jkms.2009.24.2.289

Abstract

The standard iron-chelator deferoxamine is known to prevent the growth of coagulase-negative staphylococci (CoNS) which are major pathogens in iron-overloaded patients. However, we found that deferoxamine rather promotes the growth of coagulase-positive Staphylococcus aureus. Accordingly, we tested whether deferiprone, a new clinically-available iron-chelator, can prevent the growth of S. aureus strains as well as CoNS. Deferiprone did not at least promote the growth of all S. aureus strains (n=26) and CoNS (n=27) at relatively low doses; moreover, it could significantly inhibit the growth of all staphylococci on non-transferrin-bound-iron and the growth of all CoNS on transferrin-bound iron at relatively high doses. At the same doses, it did not at least promote the growth of all S. aureus strains on transferrin-bound-iron. These findings indicate that deferiprone can be useful to prevent staphylococcal infections, as well as to improve iron overload, in iron-overloaded patients.

Keyword

Staphylococcus; Iron; Deferoxamine; Deferiprone; Transferrin

MeSH Terms

Deferoxamine/pharmacology
Humans
Iron/metabolism
Iron Chelating Agents/*pharmacology
Iron Overload/metabolism
Microbial Sensitivity Tests
Pyridones/*pharmacology
Staphylococcus/*drug effects/growth & development
Staphylococcus aureus/drug effects/growth & development
Transferrin/metabolism

Figure

• 

  Fig. 1 Examples of responses of staphylococci to deferoxamine. Staphylococcus aureus KCTC1927, Staphylococcus epidermidis KCTC1917, Staphylococcus saprophyticus KCTC3345 and a coagulase-negative staphylococcus (CoNS: S. epidermidis) strain were preconditioned by culturing in BHI broth containing 200 µM of dipyridyl at 37℃ overnight to adapt to iron-restricted conditions and to reduce intracellular iron stores. About 103-4 cfu of these three strains were spread onto the surface of SSD agar containing 1 µM FeCl3, and then discs containing 30 µL of phosphate-buffered saline (PBS) or 100 µM deferoxamine were placed on the agar surface. S. aureus KCTC1927 was incubated at 37℃ for 24 hr, and S. epidermidis KCTC1917, S. saprophyticus KCTC3345 and the CoNS strain for 48 hr.

• 

  Fig. 2 Effect of deferiprone on the growths of staphylococci on non-transferrin-bound iron. The preconditioned s KCTC1927, Staphylococcus epidermidis KCTC1917 and Staphylococcus saprophyticus KCTC3345 strains were inoculated into SSD broth containing 1 µM FC or in SSD broth containing 1 µM FC plus 0.5-1.5 mM deferiprone (DFP) at ca. 1×106 cfu/mL, and then cultured with vigorous shaking (220 rpm) at 37℃ for 24 hr. During culture, aliquots were withdrawn at appropriate times, and bacterial growths were monitored by measuring OD600 values. Results are expressed as means±standard errors.

• 

  Fig. 3 Effect of deferiprone on the growths of staphylococci on transferrin-bound iron. The preconditioned Staphylococcus aureus KCTC1927, Staphylococcus epidermidis KCTC1917 and Staphylococcus saprophyticus KCTC3345 were inoculated into SSD broth containing 0.5 mg/mL HT or in SSD broth containing 0.5 mg/mL HT plus 0.5-1.5 mM deferiprone (DFP) at ca. 1×106 cfu/mL, and then cultured with vigorous shaking (220 rpm) at 37℃ for 24 hr. The other abbreviations and symbols are as in Fig. 2.

• 

  Fig. 4 Utilization of transferrin-bound iron by staphylococci in the absence or presence of deferiprone. During culture in SSD broth containing holotransferrin (HT) or in SSD broth containing HT plus deferiprone (DFP), as shown in Fig. 3, culture supernatants were obtained by centrifuging culture aliquots at 10,000 rpm for 5 min at appropriate times. Equal volumes (20 µL) of culture supernatants were electrophoresed on 6 M urea-polyacrylamide gels, and stained with Coomassie blue. AP, MC, MN, and DF indicate apoferric, C-terminal monoferric, N-terminal monoferric and diferric transferrins, respectively.

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