Staphylococcus lugdunensis IsdG Liberates Iron from Host Heme

Haley, Kathryn P.; Janson, Eric M.; Heilbronner, Simon; Foster, Timothy J.; Skaar, Eric P.

doi:10.1128/jb.00436-11

Cited by 44 publications

(40 citation statements)

References 41 publications

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“…The S. lugdunensis proteins IsdB, IsdC, IsdJ, and IsdK were induced in cultures grown in iron-deficient medium. This is consistent with a report by Haley et al that studied the role of S. lugdunensis heme monooxygenase (IsdG) (28). These findings suggest that transcription of the isd locus in S. lugdunensis, like S. aureus, is regulated by the irondependent repressor Fur.…”

Section: Discussionsupporting

confidence: 82%

Iron-Regulated Surface Determinant (Isd) Proteins of Staphylococcus lugdunensis

et al. 2012

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bStaphylococcus lugdunensis is the only coagulase-negative Staphylococcus species with a locus encoding iron-regulated surface determinant (Isd) proteins. In Staphylococcus aureus, the Isd proteins capture heme from hemoglobin and transfer it across the wall to a membrane-bound transporter, which delivers it into the cytoplasm, where heme oxygenases release iron. The Isd proteins of S. lugdunensis are expressed under iron-restricted conditions. We propose that S. lugdunensis IsdB and IsdC proteins perform the same functions as those of S. aureus. S. lugdunensis IsdB is the only hemoglobin receptor within the isd locus. It specifically binds human hemoglobin with a dissociation constant (K d ) of 23 nM and transfers heme on IsdC. IsdB expression promotes bacterial growth in an iron-limited medium containing human hemoglobin but not mouse hemoglobin. This correlates with weak binding of IsdB to mouse hemoglobin in vitro. Unlike IsdB and IsdC, the proteins IsdJ and IsdK are not sorted to the cell wall in S. lugdunensis. In contrast, IsdJ expressed in S. aureus and Lactococcus lactis is anchored to peptidoglycan, suggesting that S. lugdunensis sortases may differ in signal recognition or could be defective. IsdJ and IsdK are present in the culture supernatant, suggesting that they could acquire heme from the external milieu. The IsdA protein of S. aureus protects bacteria from bactericidal lipids due to its hydrophilic C-terminal domain. IsdJ has a similar region and protected S. aureus and L. lactis as efficiently as IsdA but, possibly due to its location, was less effective in its natural host.

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Section: Discussionsupporting

confidence: 82%

Iron-Regulated Surface Determinant (Isd) Proteins of Staphylococcus lugdunensis

et al. 2012

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“…The pathogenic potential of S. lugdunensis, which is thus closer to that of S. aureus than those of other coagulase-negative staphylococci, may be related to virulence factors such as a fibrinogenbinding protein (25), a von Willebrand factor-binding protein (26), or synergistic hemolysins (7). In addition, the genome of S. lugdunensis N920143 contains an isd locus (19), which encodes proteins involved in iron acquisition in S. lugdunensis (18) or in cutaneous colonization in S. aureus (6).…”

Section: S Ince Its First Description In 1988 Staphylococcus Lugdunementioning

confidence: 99%

Multilocus Sequence Typing Analysis of Staphylococcus lugdunensis Implies a Clonal Population Structure

et al. 2012

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Staphylococcus lugdunensis is recognized as one of the major pathogenic species within the genus Staphylococcus , even though it belongs to the coagulase-negative group. A multilocus sequence typing (MLST) scheme was developed to study the genetic relationships and population structure of 87 S. lugdunensis isolates from various clinical and geographic sources by DNA sequence analysis of seven housekeeping genes ( aroE , dat , ddl , gmk , ldh , recA , and yqiL ). The number of alleles ranged from four ( gmk and ldh ) to nine ( yqiL ). Allelic profiles allowed the definition of 20 different sequence types (STs) and five clonal complexes. The 20 STs lacked correlation with geographic source. Isolates recovered from hematogenic infections (blood or osteoarticular isolates) or from skin and soft tissue infections did not cluster in separate lineages. Penicillin-resistant isolates clustered mainly in one clonal complex, unlike glycopeptide-tolerant isolates, which did not constitute a distinct subpopulation within S. lugdunensis . Phylogenies from the sequences of the seven individual housekeeping genes were congruent, indicating a predominantly mutational evolution of these genes. Quantitative analysis of the linkages between alleles from the seven loci revealed a significant linkage disequilibrium, thus confirming a clonal population structure for S. lugdunensis . This first MLST scheme for S. lugdunensis provides a new tool for investigating the macroepidemiology and phylogeny of this unusually virulent coagulase-negative Staphylococcus .

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“…Besides, S. lugdunensis is unique among the CoNS in that it contains a gene encoding an ironregulated surface determinant (Isd) system (30), which shares significant structural and functional homology with the Isd receptors of S. aureus. Under iron-restricted conditions, the Isd proteins cooperate to capture heme and transfer it across the wall into the cytoplasm, where it is degraded to iron for use in cellular processes (31,32). Interestingly, the genome sequencing of two strains of S. lugdunensis, N920143 (30) and HKU09-01 (33), revealed genes encoding putative virulence factors, such as adhesins, toxins, and hemolysins.…”

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Multi-Virulence-Locus Sequence Typing of Staphylococcus lugdunensis Generates Results Consistent with a Clonal Population Structure and Is Reliable for Epidemiological Typing

et al. 2014

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cStaphylococcus lugdunensis is an emergent virulent coagulase-negative staphylococcus responsible for severe infections similar to those caused by Staphylococcus aureus. To understand its potentially pathogenic capacity and have further detailed knowledge of the molecular traits of this organism, 93 isolates from various geographic origins were analyzed by multi-virulence-locus sequence typing (MVLST), targeting seven known or putative virulence-associated loci (atlL R2 , atlL R3 , hlb, isdJ, SLUG_09050, SLUG_16930, and vwbl). The polymorphisms of the putative virulence-associated loci were moderate and comparable to those of the housekeeping genes analyzed by multilocus sequence typing (MLST). However, the MVLST scheme generated 43 virulence types (VTs) compared to 20 sequence types (STs) based on MLST, indicating that MVLST was significantly more discriminating (Simpson's index [D], 0.943). No hypervirulent lineage or cluster specific to carriage strains was defined. The results of multilocus sequence analysis of known and putative virulence-associated loci are consistent with a clonal population structure for S. lugdunensis, suggesting a coevolution of these genes with housekeeping genes. Indeed, the nonsynonymous to synonymous evolutionary substitutions (d N /d S ) ratio, the Tajima's D test, and Single-likelihood ancestor counting (SLAC) analysis suggest that all virulence-associated loci were under negative selection, even atlL R2 (AtlL protein) and SLUG_16930 (FbpA homologue), for which the d N /d S ratios were higher. In addition, this analysis of virulence-associated loci allowed us to propose a trilocus sequence typing scheme based on the intragenic regions of atlL R3 , isdJ, and SLUG_16930, which is more discriminant than MLST for studying short-term epidemiology and further characterizing the lineages of the rare but highly pathogenic S. lugdunensis.

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Staphylococcus lugdunensis IsdG Liberates Iron from Host Heme

Cited by 44 publications

References 41 publications

Iron-Regulated Surface Determinant (Isd) Proteins of Staphylococcus lugdunensis

Iron-Regulated Surface Determinant (Isd) Proteins of Staphylococcus lugdunensis

Multilocus Sequence Typing Analysis of Staphylococcus lugdunensis Implies a Clonal Population Structure

Multi-Virulence-Locus Sequence Typing of Staphylococcus lugdunensis Generates Results Consistent with a Clonal Population Structure and Is Reliable for Epidemiological Typing

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