FhuD1, a Ferric Hydroxamate-binding Lipoprotein in Staphylococcus aureus

Staphylococcus aureus can utilize ferric hydroxamates as a source of iron under iron-restricted growth conditions. Proteins involved in this transport process are: FhuCBG, which encodes a traffic ATPase; FhuD2, a post-translationally modified lipoprotein that acts as a high affinity receptor at the cytoplasmic membrane for the efficient capture of ferric hydroxamates; and FhuD1, a protein with similarity to FhuD2. Gene duplication likely gave rise to fhuD1 and fhuD2. While the genomic locations of fhuCBG and fhuD2 in S. aureus strains are conserved, both the presence and the location of fhuD1 are variable. The apparent redundancy of FhuD1 led us to examine the role of this protein. We demonstrate that FhuD1 is expressed only under conditions of iron limitation through the regulatory activity of Fur. FhuD1 fractions with the cell membrane and binds hydroxamate siderophores but with lower affinity than FhuD2. Using small angle x-ray scattering, the solution structure of FhuD1 resembles that of FhuD2, and only a small conformational change is associated with ferrichrome binding. FhuD1, therefore, appears to be a receptor for ferric hydroxamates, like FhuD2. Our data to date suggest, however, that FhuD1 is redundant to FhuD2 and plays a minor role in hydroxamate transport. However, given the very real possibility that we have not yet identified the proper conditions where FhuD1 does provide an advantage over FhuD2, we anticipate that FhuD1 serves an enhanced role in the transport of untested hydroxamate siderophores and that it may play a prominent role during the growth of S. aureus in its natural environments. Staphylococcus aureus can utilize ferric hydroxamates as a source of iron under iron-restricted growth conditions. Proteins involved in this transport process are: FhuCBG, which encodes a traffic ATPase; FhuD2, a post-translationally modified lipoprotein that acts as a high affinity receptor at the cytoplasmic membrane for the efficient capture of ferric hydroxamates; and FhuD1, a protein with similarity to FhuD2. Gene duplication likely gave rise to fhuD1 and fhuD2. While the genomic locations of fhuCBG and fhuD2 in S. aureus strains are conserved, both the presence and the location of fhuD1 are variable. The apparent redundancy of FhuD1 led us to examine the role of this protein. We demonstrate that FhuD1 is expressed only under conditions of iron limitation through the regulatory activity of Fur. FhuD1 fractions with the cell membrane and binds hydroxamate siderophores but with lower affinity than FhuD2. Using small angle x-ray scattering, the solution structure of FhuD1 resembles that of FhuD2, and only a small conformational change is associated with ferrichrome binding. FhuD1, therefore, appears to be a receptor for ferric hydroxamates, like FhuD2. Our data to date suggest, however, that FhuD1 is redundant to FhuD2 and plays a minor role in hydroxamate transport. However, given the very real possibility that we have not yet identified the proper conditions where FhuD1 does provide an advantage over FhuD2, we anticipate that FhuD1 serves an enhanced role in the transport of untested hydroxamate siderophores and that it may play a prominent role during the growth of S. aureus in its natural environments. With few exceptions, all bacteria have an absolute requirement for iron (1Posey J.E. Gherardini F.C. Science. 2000; 288: 1651-1653Crossref PubMed Scopus (401) Google Scholar, 2Weinberg E.D. Perspect. Biol. Med. 1997; 40: 578-583Crossref PubMed Scopus (126) Google Scholar). The amount of free, biologically relevant iron, however, is negligible at physiological pH (10-18m) (3Braun V. Hantke K. Köster W. Met. Ions Biol. Syst. 1998; 35: 67-145PubMed Google Scholar). This is primarily caused by the rapid formation of iron(III)-hydroxy precipitates that are highly insoluble. In response to the stress generated from a low iron environment, many microorganisms secrete low molecular weight iron chelating compounds termed siderophores. Siderophores commonly bind ferric iron with extremely high affinities (4Byers B.R. Arceneaux E.L. Sigel A. Sigel H. Iron Transport and Storage in Microorganisms, Plants, and Animals. 35. Marcel Dekker, Inc., New York1998: 37-66Google Scholar) and serve to solubilize iron from the biologically inert iron(III)-hydroxy precipitates. Typically, ferric-siderophores are mobilized across the cell envelope of Gram-negative bacteria expressing cognate outer membrane receptors, periplasmic-binding proteins, and associated ABC 1The abbreviations used are: ABC, ATP-binding cassette; SAXS, small angle x-ray scattering; MBP, maltose-binding protein.-type transporters (5Köster W. Res. Microbiol. 2001; 152: 291-301Crossref PubMed Scopus (213) Google Scholar, 6Ratledge C. Dover L.G. Annu. Rev. Microbiol. 2000; 54: 881-941Crossref PubMed Scopus (1176) Google Scholar). In Gram-positive bacteria, ferric siderophores are captured by lipoproteins that function as high affinity receptors and subsequently feed ligand to the ABC transporter in the cytoplasmic membrane. The lipid group on these receptors acts as a tether to anchor the receptor protein to the external face of the cell membrane (7Sutcliffe I.C. Russell R.R.B. J. Bacteriol. 1995; 177: 1123-1128Crossref PubMed Scopus (332) Google Scholar). Whereas Staphylococcus aureus isolates produce endogenous siderophores (8Courcol R.J. Trivier D. Bissinger M-C. Martin G.R. Brown M. R. W Infect. Immun. 1997; 65: 1944-1948Crossref PubMed Google Scholar, 9Dale S.E. Doherty-Kirby A. Lajoie G. Heinrichs D.E. Infect Immun. 2004; 72: 29-37Crossref PubMed Scopus (167) Google Scholar, 10Drechsel H. Freund S. Nicholson G. Haag H. Jung O. Zähner H. Jung G. BioMetals. 1993; 6: 185-192Crossref PubMed Scopus (95) Google Scholar, 11Konetschny-Rapp S. Jung G. Meiwes J. Zähner H. Eur. J. Biochem. 1990; 191: 65-74Crossref PubMed Scopus (134) Google Scholar), S. aureus utilizes others that are produced by other microorganisms (so-called xenosiderophores) for growth under conditions of iron deprivation. One group of xenosiderophores that S. aureus can utilize is the hydroxamate-class of siderophore, including aerobactin, coprogen, ferrioxamine B (Desferal™), ferrichrome, and rhodotorulic acid (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar). In our previous studies, we showed that S. aureus strain RN6390 possessed at least five different iron-regulated genes whose products were involved in the ferric hydroxamate uptake process (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar, 13Sebulsky M.T. Hohnstein D. Hunter M.D. Heinrichs D.E. J. Bacteriol. 2000; 182: 4394-4400Crossref PubMed Scopus (110) Google Scholar, 14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). A three gene operon, fhuCBG, encodes a classical traffic ATPase (for a review of traffic ATPases, see Ref. 15Ames G.F. Mimura C.S. Holbrook S.R. Shyamala V. Adv. Enzymol. Relat. Areas Mol. Biol. 1992; 65: 1-47PubMed Google Scholar) while a fourth gene, fhuD2, codes for a lipoprotein (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar) that functions as a high affinity receptor for aerobactin, coprogen, Desferal™, ferrichrome, and rhodotorulic acid (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). The fifth gene involved in this transport system, fhuD1, is predicted to encode a protein with 50% total similarity to FhuD2. We showed that the fhuD1 gene product could partially compensate for the loss of the fhuD2 gene product (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar). In this communication, we show that the presence and location of fhuCBG and fhuD2 are strictly conserved in several S. aureus genomes. In contrast, the fhuD1 gene is mobile: it is in strains and appears on a genomic in The of the fhuD1 gene a of the function of the FhuD1 protein. and aureus RN6390 J. J. Bacteriol. PubMed Scopus Google Scholar) as the strain in this and and have (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar, 13Sebulsky M.T. Hohnstein D. Hunter M.D. Heinrichs D.E. J. Bacteriol. 2000; 182: 4394-4400Crossref PubMed Scopus (110) Google Scholar). used for and protein the of S. the growth and the for were by the of S. aureus in with to and iron-restricted growth as of a of of of to of of and in of and the pH to to of and of acid acid and were and the to with and were in S. aureus growth for the growth of and fhuD1 gene, the predicted as a with and were the and and (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). The from which a and FhuD1 is strain to strain to an of the of growth to for the were The at to and across a for the protein by the at in pH it to an and a of to FhuD1 used to in New of protein in The were with of protein at and at the were and were were three over cell to and aureus in were three with and to an of The cell by to as (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). on the were with by the of were to and were the as the In all the FhuD1 and the used at a FhuD1 were a FhuD1 protein used at a of the of pH and the at The and were at and with and at and were as (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). FhuD1 protein with and at for in the presence of The pH were to in for and by as J. A Scholar). from B as from the and and were from by A. D. R. K. H. 1997; PubMed Scopus (213) Google Scholar). were as M.T. Hohnstein D. Hunter M.D. Heinrichs D.E. J. Bacteriol. 2000; 182: 4394-4400Crossref PubMed Scopus (110) Google Scholar). of ferric at as in were on were the at a of were at for by at of hydroxamate siderophores on S. in of of growth are in a a in of of growth are for FhuD2 were as (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). for FhuD1 were at the as the and the protein solution through a during the of the to the of were at a with at a of to the where is as is the while is the of the that used in the is as were that of from the protein solution by of the were A. Scholar, A. Scholar), and a The three protein solution and were and and the with from the protein solution to from the protein. In our previous that the of the FhuD2 protein in (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar), we showed that of FhuD2 that FhuD2 and in the cell and that FhuD2 ferric hydroxamates with in the to The data that the protein acts as a high affinity receptor for hydroxamate siderophores at the external face of the cytoplasmic membrane in S. aureus (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar, 14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). In our studies, however, we identified a gene, fhuD1, that predicted to encode a protein with similarity to FhuD2 (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar). of the of fhuD1 and fhuD2 strains that the fhuD1 gene product could partially compensate for the loss of fhuD2 in of the transport of hydroxamate siderophores. The were to the function of of fhuD1 in S. that FhuD1 is in to FhuD2 than to other from the of other Gram-positive bacteria that from a gene duplication at in the of S. S. aureus in the process of were for the presence of S. aureus M.T. R. A. C. C. C. A. J. H. S. K. A. R. S. K. D. K. M. S. M. K. S. J. S. A. 2004; PubMed Scopus Google Scholar), M.T. R. A. C. C. C. A. J. H. S. K. A. R. S. K. D. K. M. S. M. K. S. J. S. A. 2004; PubMed Scopus Google Scholar), M. H. A. K. J. M. H. A. H. A. R. C. K. H. S. S. J. M. A. K. K. C. M. H. K. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar), M. H. A. K. J. M. H. A. H. A. R. C. K. H. S. S. J. M. A. K. K. C. M. H. K. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar), and M. H. K. A. K. H. K. K. Full Text Full Text PDF PubMed Scopus Google Scholar). in A and fhuCBG and fhuD2 are in the genomic locations in all genomes. In contrast, fhuD1 is only in five and In of these and the fhuD1 gene is in a genomic while in the the fhuD1 on a genomic to as M. H. A. K. J. M. H. A. H. A. R. C. K. H. S. S. J. M. A. K. K. C. M. H. K. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). The identified by M. H. A. K. J. M. H. A. H. A. R. C. K. H. S. S. J. M. A. K. K. C. M. H. K. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar) as However, our showed that encodes a protein. The fhuD1 is the is to that the presence of fhuD1 is with the presence of the a predicted acid protein with similarity to a involved in The genes are and in and and are both from the genomic location in and and is a and a in the of and M. H. A. K. J. M. H. A. H. A. R. C. K. H. S. S. J. M. A. K. K. C. M. H. K. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). The of the fhuD1 gene the of S. aureus a of the fhuD1 gene S. aureus fhuD1 an of S. aureus RN6390 and were by in iron-restricted were to a that cell three and are the In we show that FhuD1 with the that the protein is and associated with the membrane. have for several other lipoproteins (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar, A. K. C. Infect. Immun. 1998; PubMed Google Scholar, C. Microbiol. 2003; PubMed Scopus Google Scholar). This is with the presence of a in FhuD1 I.C. PubMed Scopus Google Scholar). Our that FhuD1, primarily the membrane of the of FhuD1 in the cell membrane by iron FhuD1 is only in in and this is by the activity of the a FhuD1 in the membrane of under conditions is in the with protein from that the is for FhuD1 and does not with FhuD2. FhuD1 Siderophores but with previous identified a role for fhuD1 in ferric hydroxamate uptake a fhuD2 strain that expressed fhuD1 could utilize ferric hydroxamates, to a than RN6390 (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar). FhuD1 50% total similarity with FhuD2 (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar, 14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar), a protein that our group as a high affinity receptor for ferric hydroxamates (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar), we that FhuD1 is a receptor for ferric this and as an to demonstrate that ferric hydroxamates with FhuD1, we in the products of FhuD1 with with ferric siderophores We showed that the of FhuD1 from with coprogen, ferrichrome but not with the the does not the growth of S. aureus in The of the in these not but is likely partially FhuD1 as a of in the presence of siderophores. In the presence of an it is that FhuD1 a that is to a of ligand we used to the affinity of FhuD1 for ferric hydroxamates, and the are in with FhuD2, FhuD1 a lower affinity for ferrichrome, and and a lower affinity for The low affinity of FhuD1 for is with our that does not FhuD1 from of FhuD1 for ferric hydroxamate aureus have S. aureus have (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, V. Köster W. J. Bacteriol. 1995; 177: PubMed Google Scholar). in a of on the of a change with cognate in contrast, FhuD2 only a very small conformational change (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). the of ligand on the of FhuD1, we used to the change in of FhuD1 it binds ferrichrome, the for which FhuD1 the data can be used to the of which is as the of all from of as the a of the of the and in the in The is a A. G. of Inc., New Scholar), and for FhuD1 in the presence of as for FhuD1, that the protein is in these we an of for the of the and for the This in of is a minor and is only of the very high of the it that the protein a maltose-binding protein a conformational change that by x-ray 1992; PubMed Scopus Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar), and the of a of it binds in solution B.H. M. J. Mol. Biol. PubMed Scopus Google Scholar). the change in FhuD1, in we have the for the and of In a is that the the protein and the as a of the from the protein. are the in the angle however, of the very from the protein at these this of the is not as can be from the in the the other is a in the in the with the this of the a from a to a This change is but to is with We have FhuD2 (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). A of the data from both FhuD2 and FhuD1 is in The solution x-ray from the proteins, in both the and is in the only at high these may be to minor the high of the in the that the and of the be a of only FhuD1 to S. aureus with Siderophores as of that FhuD1, like FhuD2, is a receptor for ferric hydroxamate siderophores and is to transport of siderophores the This led us to the of the presence of FhuD1 is biologically to S. this we used the with of and the of growth for RN6390 strain and its and the of these are in of FhuD1 on the of the to of the that it advantage to are expressing FhuD2. In contrast, of FhuD2 in that not on coprogen, and high of ferrichrome and for The of coprogen, at high to the growth of a strain not expressing FhuD2 given it to FhuD1 with affinity however, were the for ferrichrome, given the high affinity of FhuD1 and FhuD2 for this in growth are not caused by in protein by we of FhuD1 and FhuD2 in RN6390 not that not only is affinity for the a role in the growth but that FhuD1 and the are likely than of FhuD2 with the membrane transport these the that FhuD2 is the receptor for ferric hydroxamate transport in S. aureus and demonstrate that the presence of a high protein does not in efficient transport. The to iron from the is to the growth of all S. aureus ferric iron associated with siderophores through the hydroxamate The in many S. aureus strains is of five FhuD1, FhuD2, and The of a traffic ATPase and are membrane and of an that is for the of siderophores in S. aureus M.T. Hohnstein D. Hunter M.D. Heinrichs D.E. J. Bacteriol. 2000; 182: 4394-4400Crossref PubMed Scopus (110) Google Scholar). The fhuD2 gene encodes an iron-regulated lipoprotein that high affinity for siderophores and the affinity of FhuD2 for siderophores is than that of (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, V. Köster W. J. Bacteriol. 1995; 177: PubMed Google Scholar). In this communication, we have our of the in S. aureus by the FhuD1 protein and its role in the transport We have that FhuD1 a lipoprotein in S. aureus that acts as a receptor for ferric hydroxamate but that it functions to a than FhuD2 in this we not have we that both FhuD1 and FhuD2 with the with in the membrane of and a S. aureus RN6390 a in is of ferric hydroxamates M.T. Hohnstein D. Hunter M.D. Heinrichs D.E. J. Bacteriol. 2000; 182: 4394-4400Crossref PubMed Scopus (110) Google Scholar), the possibility of transporters that with the FhuD1 and FhuD2 the similarity FhuD1 and FhuD2 is to the of FhuD1 and FhuD2 are extremely which be given all that were in FhuD2 in an (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar), that gave rise to that a ferric hydroxamate transport are conserved in FhuD1 binds with lower affinity than FhuD2 an for the in in for strains expressing only of FhuD1 FhuD2, and the of in that to FhuD2 but not FhuD1 from by K. that the affinities of FhuD1 and FhuD2 for ferrichrome are the of ferrichrome on a strain expressing FhuD2 is than on an strain expressing only to the that FhuD2 with the transport than does However, an that FhuD2 binds ligand in a different that for the transport We that the of the that is by the membrane transporter (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar). ABC transporters involved in the transport of and a and only a few of this transporter (5Köster W. Res. Microbiol. 2001; 152: 291-301Crossref PubMed Scopus (213) Google Scholar). This of from the of the structure of this the where the of the structure are by a that is of at the of the the of the of are by a that an the of the protein. This structure is to in an of these to conformational ligand binding. high of and in both the and this is to be the J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus Google Scholar, Biol. 6: PubMed Scopus Google Scholar, J. Bacteriol. PubMed Scopus Google Scholar). Our in both FhuD1 and FhuD2 from S. aureus not demonstrate a conformational in with high of other of this protein The conformational change associated with ferrichrome by FhuD1 resembles that associated with the of by by x-ray J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus Google Scholar). In contrast, we that the of by FhuD2 by an extremely small conformational change (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar), and our from this show a conformational change in FhuD1 it binds are that these The is that the siderophores produce different in protein in other the conformational change in both FhuD1 and FhuD2 may be the bind ferrichrome with In of this of FhuD2 that the protein an of while and FhuD2 have of and A possibility is that the conformational change in FhuD2 it binds the data for the were several different and were data and to produce the In contrast, the data for the were at a a and In these could be by in the conformational are very only high provide a to this that a conformational change can in a protein that is to is and that the ligand may a structure the This for three S. Köster W. Mol. 1995; PubMed Scopus Google Scholar) and S. aureus FhuD2 (14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar) and FhuD1 Whereas fhuD2 and fhuCBG genes are in all S. aureus strains whose have the fhuD1 gene is not In an to provide an for this we have the of S. aureus The by the of and the other by the of and M.T. Microbiol. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). This is with of data that is from other S. aureus The of fhuD1 and fhuD2 genes in that these genes by a gene duplication but that the of the is in the of the of fhuD1 genes in S. aureus One the gene duplication the of the on the to the group the gene duplication may have the of S. aureus This however, that the fhuD1 gene subsequently in the to genomic and data that the fhuD1 gene from the to This loss may have the of a by fhuD1 is in to as a and a genomic of data that the fhuD1 gene to the S. aureus the gene duplication This is from the of the as an gene the fhuD1 gene, and both genes are on a genomic in all where fhuD1 is it to the which is from the of strains that the fhuD1 This of fhuD1 and and with that genes are as a to the that of the S. aureus is of that are associated with functions M.T. Microbiol. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). The of the is of which are to by these genes provide a advantage to S. aureus in environments. is to that fhuD1 is gene, as it is on a genomic (12Sebulsky M.T. Heinrichs D.E. J. Bacteriol. 2001; 183: 4994-5000Crossref PubMed Scopus (87) Google Scholar, 14Sebulsky M.T. Shilton B.H. Speziali C.D. Heinrichs D.E. J. Biol. Chem. 2003; 278: 49890-49900Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar), in to the data in this communication, demonstrate the FhuD1 and FhuD2 A in the of siderophores by R. Hantke K. Mol. Microbiol. 1993; PubMed Scopus Google Scholar) and transport in and D. C. V. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, G. J. Mol. Biol. PubMed Scopus Google Scholar). The apparent redundancy these may a advantage in our data that FhuD2 is the relevant our is on data from in the with a small of hydroxamate siderophores. However, the of FhuD1 in S. aureus that it likely serves an enhanced role in the transport of untested hydroxamate siderophores and to the of S. aureus in its natural environments. We J. K. for on the We are to the Staphylococcus aureus with from the of and the and to The for and the for

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