Siderophore-based Iron Acquisition and Pathogen Control

Overview

Journal Microbiol Mol Biol Rev

Publisher American Society for Microbiology

Specialty Microbiology

Date 2007 Sep 7

PMID 17804665

Citations 609

Authors

Marcus Miethke

Mohamed A Marahiel

Affiliations

Soon will be listed here.

Abstract

High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as "Trojan horse" toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.

Citing Articles

Flavin-containing siderophore-interacting protein of Shewanella putrefaciens DSM 9451 reveals common structural and functional aspects of ferric-siderophore reduction.

Trindade I, Fonseca B, Catarino T, Matias P, Moe E, Louro R J Biol Inorg Chem. 2025; .

PMID: 40080164 DOI: 10.1007/s00775-025-02106-z.

Self-growth suppression in is caused by a diffusible antagonist.

Sandhu A, Fischer B, Subramanian S, Hoppe A, Brozel V ISME Commun. 2025; 5(1):ycaf032.

PMID: 40071143 PMC: 11896636. DOI: 10.1093/ismeco/ycaf032.

Exploring the plant growth promoting attributes of pteridophyte-associated microbiome for agricultural sustainability.

Swain S, Nayak S, Mishra S, Ghana M, Dash D Physiol Mol Biol Plants. 2025; 31(2):211-232.

PMID: 40066462 PMC: 11890681. DOI: 10.1007/s12298-025-01553-x.

Antibiotic resistance and virulence profile of isolated from wild Sumatran Orangutans ().

Afiff U, Hidayat R, Indrawati A, Sunartatie T, Hardiati A, Rotinsulu D J Adv Vet Anim Res. 2025; 11(4):1066-1075.

PMID: 40013287 PMC: 11855422. DOI: 10.5455/javar.2024.k858.

Contribution of fepA, fciABC, sbaA, sbaBCDEF, and feoB to ferri-stenobactin acquisition in Stenotrophomonas maltophilia KJ.

Yeh T, Lu H, Li L, Lin Y, Yang T BMC Microbiol. 2025; 25(1):91.

PMID: 40000954 PMC: 11852561. DOI: 10.1186/s12866-025-03792-0.

References

Stefanska A, Fulston M, Jones J, Warr S . A potent seryl tRNA synthetase inhibitor SB-217452 isolated from a Streptomyces species. J Antibiot (Tokyo). 2001; 53(12):1346-53. DOI: 10.7164/antibiotics.53.1346. View

Luo M, Fadeev E, Groves J . Mycobactin-mediated iron acquisition within macrophages. Nat Chem Biol. 2006; 1(3):149-53. DOI: 10.1038/nchembio717. View

Adjimani J, Emery T . Iron uptake in Mycelia sterilia EP-76. J Bacteriol. 1987; 169(8):3664-8. PMC: 212448. DOI: 10.1128/jb.169.8.3664-3668.1987. View

Georgatsou E, Alexandraki D . Regulated expression of the Saccharomyces cerevisiae Fre1p/Fre2p Fe/Cu reductase related genes. Yeast. 1999; 15(7):573-84. DOI: 10.1002/(SICI)1097-0061(199905)15:7<573::AID-YEA404>3.0.CO;2-7. View

Quiocho F, Ledvina P . Atomic structure and specificity of bacterial periplasmic receptors for active transport and chemotaxis: variation of common themes. Mol Microbiol. 1996; 20(1):17-25. DOI: 10.1111/j.1365-2958.1996.tb02484.x. View

Munkelt D, Grass G, Nies D . The chromosomally encoded cation diffusion facilitator proteins DmeF and FieF from Wautersia metallidurans CH34 are transporters of broad metal specificity. J Bacteriol. 2004; 186(23):8036-43. PMC: 529076. DOI: 10.1128/JB.186.23.8036-8043.2004. View

Poey M, Azpiroz M, Lavina M . Comparative analysis of chromosome-encoded microcins. Antimicrob Agents Chemother. 2006; 50(4):1411-8. PMC: 1426990. DOI: 10.1128/AAC.50.4.1411-1418.2006. View

Sprencel C, Cao Z, Qi Z, Scott D, Montague M, Ivanoff N . Binding of ferric enterobactin by the Escherichia coli periplasmic protein FepB. J Bacteriol. 2000; 182(19):5359-64. PMC: 110977. DOI: 10.1128/JB.182.19.5359-5364.2000. View

Hantke K . Iron and metal regulation in bacteria. Curr Opin Microbiol. 2001; 4(2):172-7. DOI: 10.1016/s1369-5274(00)00184-3. View

10.

Saier Jr M, Beatty J, Goffeau A, Harley K, Heijne W, Huang S . The major facilitator superfamily. J Mol Microbiol Biotechnol. 2000; 1(2):257-79. View

11.

Stoj C, Augustine A, Zeigler L, Solomon E, Kosman D . Structural basis of the ferrous iron specificity of the yeast ferroxidase, Fet3p. Biochemistry. 2006; 45(42):12741-9. DOI: 10.1021/bi061543+. View

12.

Bernier G, Girijavallabhan V, Murray A, Niyaz N, Ding P, Miller M . Desketoneoenactin-siderophore conjugates for Candida: evidence of iron transport-dependent species selectivity. Antimicrob Agents Chemother. 2004; 49(1):241-8. PMC: 538862. DOI: 10.1128/AAC.49.1.241-248.2005. View

13.

OBrien I, Cox G, Gibson F . Enterochelin hydrolysis and iron metabolism in Escherichia coli. Biochim Biophys Acta. 1971; 237(3):537-49. DOI: 10.1016/0304-4165(71)90274-1. View

14.

Puig S, Askeland E, Thiele D . Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation. Cell. 2005; 120(1):99-110. DOI: 10.1016/j.cell.2004.11.032. View

15.

Moore D, Earhart C . Specific inhibition of Escherichia coli ferrienterochelin uptake by a normal human serum immunoglobulin. Infect Immun. 1981; 31(2):631-5. PMC: 351355. DOI: 10.1128/iai.31.2.631-635.1981. View

16.

Bouige P, Laurent D, Piloyan L, Dassa E . Phylogenetic and functional classification of ATP-binding cassette (ABC) systems. Curr Protein Pept Sci. 2002; 3(5):541-59. DOI: 10.2174/1389203023380486. View

17.

Tsafack A, Loyevsky M, Ponka P, Cabantchik Z . Mode of action of iron (III) chelators as antimalarials. IV. Potentiation of desferal action by benzoyl and isonicotinoyl hydrazone derivatives. J Lab Clin Med. 1996; 127(6):574-82. DOI: 10.1016/s0022-2143(96)90148-1. View

18.

Haas H, Zadra I, Stoffler G, Angermayr K . The Aspergillus nidulans GATA factor SREA is involved in regulation of siderophore biosynthesis and control of iron uptake. J Biol Chem. 1999; 274(8):4613-9. DOI: 10.1074/jbc.274.8.4613. View

19.

Raymond K, Dertz E, Kim S . Enterobactin: an archetype for microbial iron transport. Proc Natl Acad Sci U S A. 2003; 100(7):3584-8. PMC: 152965. DOI: 10.1073/pnas.0630018100. View

20.

Grewal K, Warner P, Williams P . An inducible outer membrane protein involved in aerobactin-mediated iron transport by co1V strains of Escherichia coli. FEBS Lett. 1982; 140(1):27-30. DOI: 10.1016/0014-5793(82)80513-9. View