Transferrin and Lactoferrin – Human Iron Sources for Enterococci


Share / Export Citation / Email / Print / Text size:

Polish Journal of Microbiology

Polish Society of Microbiologists

Subject: Microbiology


ISSN: 1733-1331
eISSN: 2544-4646





Volume / Issue / page

Related articles

VOLUME 66 , ISSUE 4 (December 2017) > List of articles

Transferrin and Lactoferrin – Human Iron Sources for Enterococci

Paweł Lisiecki *

Keywords : Enterococcus spp., iron acquisition, lactoferrin, siderophores, transferrin

Citation Information : Polish Journal of Microbiology. Volume 66, Issue 4, Pages 419-425, DOI:

License : (CC BY-NC-ND 4.0)

Received Date : 09-February-2017 / Accepted: 17-May-2017 / Published Online: 04-December-2017



To overcome limitations in iron acquisition, enterococci have evolved a number of mechanisms to scavenge iron from the host iron-binding proteins – transferrin (TR) and lactoferrin (LF). The aim of this study was to demonstrate the mechanisms by which enterococci utilize human TR and LF bound iron. The study included two strains of Enterococcus faecalis grown in iron-deficient and iron-excess media respectively. The binding activity of both proteins was monitored using proteins labelled with 125I. The uptake of iron by enterococciwas determined using 59Fe labelled proteins. Reduction of iron bound to TR and LF was assayed with ferrozine. The proteolytic cleavage of TR and LF was visualized by SDS-polyacrylamide gel electrophoresis. The siderophore activity was measured with chrome azurol S. The study revealed that enterococci use several ways to acquire iron from TR and LF, such as iron chelating siderophores, iron reduction – facilitated iron release, protein degradation – promoted iron release, and receptor mediated capture of the iron-host protein complexes. The broad spectrum of iron acquisition mechanisms used by enterococci may play a significant role in the colonization of the human body and the resulting pathogenicity

Content not available PDF Share



Brock J.H. and J. Ng. 1983. The effect of desferrixamine on growth of Staphylococcus aureus, Yersinia enterocolitica and Streptococcus faecalis in human serum: uptake of desferrioxamine-bound iron. FEMS Microbiol. Lett. 20: 439–442.


Clarke T.E., L.W. Tari and H.J. Vogel. 2001. Structural biology of bacterial iron uptake systems. Curr. Top Med. Chem. 1: 7–30.


Csaky T.Z. 1948. On the estimation of bound hydroxylamine in biological materials. Acta Chem. Scand. 2: 450–454.


Deneer H.G., V. Healey and I. Boychuk 1995. Reduction of exogenous ferric iron by a surface-associated ferric reductase of Listeria spp. Microbiol. 141: 1985–1992.


Drechsel H. and G. Winkelman. 1997. Iron chelation and siderophores, pp. 1–49. In: Winkelman G. and C.J. Carrano (eds). Transition metals in microbial metabolism. Harwood Academic, Amsterdam.


European Committee on Antimicrobial Susceptibility Testing (EUCAST). 2017. MIC determination of non-fastidious and fastidious organisms. EUCAST Version 7.


Fisher K. and C. Phillips. 2009. The ecology, epidemiology and virulence of Enterococcus. Microbiol. 155: 1749–1757.


Fontecave M., J. Covès and J.L. Pierre. 1994. Ferric reductases or flavin reductases? Biometals 7: 3–8.


García-Montoya I.A., T.S. Cendón, S. Arévalo-Gallegos andQ. Rascón-Cruz. 2012. Lactoferrin a multiple bioactive protein: an overview. Biochim. Biophys. Acta. 1820: 226–236.


Gilmore M.S., F. Lebreton and W. van Schaik. 2013. Genomic transition of enterococci from gut commensals to leading causes of multidrug-resistant hospital infection in the antibiotic era. Curr. Opin. Microbiol. 16:10–16.


Harris W.R., C.J. Carrano, S.R. Cooper, S.R. Sofen, A.E Avdeef, J.V. McArdle and K.N. Raymond. 1979. Coordination chemistry of microbial iron transport compounds. 19. Stability constants and electrochemical behavior of ferric enterobactin and model complexes. J. Am. Chem. Soc.101: 6097–6104.


Kanemitsu K., T. Nishino, H. Kunishima, N. Okamura, H. Takemura, H. Yamamoto and M. Kaku. 2001. Quantitative determination of gelatinase activity among enterococci. J. Microbiol. Methods 47: 11–16.


Krewulak K.D. and H.J. Vogel. 2008. Structural biology of bacterial iron uptake. Biochim. Biophys. Acta 1778: 1781–1804.


Kurth C., H. Kageb and M. Nett. 2016. Siderophores as molecular tools in medical and environmental applications. Org. Biomol. Chem. 14: 8212–8227.


Lindsay J.A., T.V. Riley and B.J. Mee. 1995. Staphylococcus aureus but not Staphylococcus epidermidis can acquire iron from transferrin. Microbiol. 141: 197–203.


Lisiecki P., P. Wysocki and J. Mikucki. 1999. Occurrence of siderophores in enterococci. Zentralbl. Bakteriol. 289: 807–815.


Marcelis J.H., H.J. den Daas-Slagt and J.A. Hoogkamp-Korstanje. 1978. Iron requirement and chelator production of staphylococci, Streptococcus faecalis and Enterobacteriaceae. Antonie Van Leeuwenhoek 44: 257–267.


Markwell M.A. 1982. A new solid-state reagent to iodinate proteins. I. Conditions for the efficient labeling of antiserum. Anal. Biochem. 125: 427–432.


Mietzner T.A. and S.A. Morse.1994. The role of iron-binding proteins in the survival of pathogenic bacteria. Annu. Rev. Nutr. 14: 471–493.


Parker Siburt C.J., T.A. Mietzner and A.L. Crumbliss. 2012. FbpA-a bacterial transferrin with more to offer. Biochim. Biophys. Acta 1820: 379–392.


Ratledge C. and L.G. Dover. 2000. Iron metabolism in pathogenic bacteria. Annu. Rev. Microbiol. 54: 881–941.


Schröder I., E. Johnson and S. de Vries. 2003. Microbial ferric iron reductases. FEMS Microbiol. Rev. 27: 427–447.


Schwyn B. and J.B. Neilands. 1987. Universal chemical assay for detection and determination of siderophores. Anal. Biochem. 160: 47–56.


Sheldon J.R., Laakso H.A. and Heinrichs D.E. 2016. Iron Acquisition Strategies of Bacterial Pathogens. Microbiol. Spectr. 4(2): 1–32.


Sobiś-Glinkowska M., J. Mikucki and P. Lisiecki. 2001a. Animal body iron sources utilized in vitro by enterococci (in Polish). Med. Dosw. Mikrobiol. 53: 9–15.


Sobiś-Glinkowska M., J. Mikucki and P. Lisiecki. 2001b. Influence of iron-restricted conditions on growth and hydroxamate siderophore release in enterococci. Acta Microbiol. Pol. 50:179–182.


Strzelecki J., W. Hryniewicz and E. Sadowy. 2011.Gelatinase-associated phenotypes and genotypes among clinical isolates of Enterococcus faecalis in Poland. Pol. J. Microbiol. 60: 287–292.


Styriak I., A. Lauková, V. Strompfová and A. Ljungh. 2004. Mode of binding of fibrinogen, fibronectin and iron-binding proteins by animal enterococci. Vet. Res. Commun. 28: 587–598.


van Tyne D., M.J. Martin and M.S. Gilmore. 2013. Structure, function, and biology of the Enterococcus faecalis cytolysin. Toxins 5: 895–911.


Vartivarian S.E., and R.E. Cowart. 1999. Extracellular iron reductases: identification of a new class of enzymes by siderophore-producing microorganisms. Arch. Biochem. Biophys. 364: 75–82.


Weinberg E.D. 2009. Iron availability and infection. Biochim. Biophys. Acta 1790: 600–605.


Williams P. and E. Griffiths. 1992. Bacterial transferrin receptors-structure, function and contribution to virulence. Med. Microbiol. Immunol. 181: 301–322.


Yuen G.J. and F.M Ausubel. 2014. Enterococcus infection biology: lessons from invertebrate host models. J. Microbiol. 52: 200–210.


Zareba T.W., C. Pascu, W. Hryniewicz and T. Wadström. 1997. Binding of extracellular matrix proteins by enterococci. Curr. Microbiol. 34: 6–11.