Existence of a Colonizing Staphylococcus aureus Strain Isolated in Diabetic Foot Ulcers

Staphylococcus aureus is an opportunistic bacterium capable of causing a wide range of severe diseases when it gains access to underlying tissues. Paradoxically, S. aureus is a common inhabitant of the skin microflora and colonizes the nares and other human mucosa. The purpose of this study was to determine the genetic basis for the differences in the pathogenic versus colonizing potential of S. aureus isolated from diabetic foot ulcers (DFUs). By performing optical map comparisons of a collection of S. aureus strains isolated from DFUs, we brought to light a prophage present in noninfecting bacteria. The phage, namely ROSA-like, was localized in a hotspot region ΦNM2 near the locus isd, the iron surface determinant system. The integrated phage significantly reduces the virulence of the strain and increases the biofilm formation. DFUs seem to be a specific niche of this colonizing strain. The ROSA-like phage represents the first description of a mobile element present mainly in S. aureus isolated from DFUs, which modulates the relationship of the bacteria with its human host. This phage appears to attenuate bacterial virulence and promote colonization

Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host-Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection

10.1371/journal.ppat.1005341PLoS Pathogens1112e100534

Specificity of Staphyloferrin B Recognition by the SirA Receptor from Staphylococcus aureus*

Many organisms use sophisticated systems to acquire growth-limiting iron. Iron limitation is especially apparent in bacterial pathogens of mammalian hosts where free iron concentrations are physiologically negligible. A common strategy is to secrete low molecular weight iron chelators, termed siderophores, and express high affinity receptors for the siderophore-iron complex. Staphylococcus aureus, a widespread pathogen, produces two siderophores, staphyloferrin A (SA) and staphyloferrin B (SB). We have determined the crystal structure of the staphyloferrin B receptor, SirA, at high resolution in both the apo and Fe(III)-SB (FeSB)-bound forms. SirA, a member of the class III binding protein family of metal receptors, has N- and C-terminal domains, each composed of mainly a β-stranded core and α-helical periphery. The domains are bridged by a single α-helix and together form the FeSB binding site. SB coordinates Fe(III) through five oxygen atoms and one nitrogen atom in distorted octahedral geometry. SirA undergoes conformational change upon siderophore binding, largely securing two loops from the C-terminal domain to enclose FeSB with a low nanomolar dissociation constant. The staphyloferrin A receptor, HtsA, homologous to SirA, also encloses its cognate siderophore (FeSA); however, the largest conformational rearrangements involve a different region of the C-terminal domain. FeSB is uniquely situated in the binding pocket of SirA with few of the contacting residues being conserved with those of HtsA interacting with FeSA. Although both SirA and HtsA bind siderophores from the same α-hydroxycarboxylate class, the unique structural features of each receptor provides an explanation for their distinct specificity