scholarly journals Staphylococcus aureus IsdB Is a Hemoglobin Receptor Required for Heme Iron Utilization

2006 ◽  
Vol 188 (24) ◽  
pp. 8421-8429 ◽  
Author(s):  
Victor J. Torres ◽  
Gleb Pishchany ◽  
Munir Humayun ◽  
Olaf Schneewind ◽  
Eric P. Skaar
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Stable Isotope ◽  
Heme Iron ◽  
Bacterial Surface ◽  
Heme Transport ◽  
Hemoglobin Binding ◽  
Human Infections ◽  
Host Tissues ◽  
Iron Utilization

ABSTRACT The pathogenesis of human infections caused by the gram-positive microbe Staphylococcus aureus has been previously shown to be reliant on the acquisition of iron from host hemoproteins. The iron-regulated surface determinant system (Isd) encodes a heme transport apparatus containing three cell wall-anchored proteins (IsdA, IsdB, and IsdH) that are exposed on the staphylococcal surface and hence have the potential to interact with human hemoproteins. Here we report that S. aureus can utilize the host hemoproteins hemoglobin and myoglobin, but not hemopexin, as iron sources for bacterial growth. We demonstrate that staphylococci capture hemoglobin on the bacterial surface via IsdB and that inactivation of isdB, but not isdA or isdH, significantly decreases hemoglobin binding to the staphylococcal cell wall and impairs the ability of S. aureus to utilize hemoglobin as an iron source. Stable-isotope-tracking experiments revealed removal of heme iron from hemoglobin and transport of this compound into staphylococci. Importantly, mutants lacking isdB, but not isdH, display a reduction in virulence in a murine model of abscess formation. Thus, IsdB-mediated scavenging of iron from hemoglobin represents an important virulence strategy for S. aureus replication in host tissues and for the establishment of persistent staphylococcal infections.

scholarly journals Distribution of Protein A on the Surface of Staphylococcus aureus

2007 ◽  
Vol 189 (12) ◽  
pp. 4473-4484 ◽  
Author(s):  
Andrea C. DeDent ◽  
Molly McAdow ◽  
Olaf Schneewind
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Laser Scanning ◽  
Protein A ◽  
Surface Proteins ◽  
Laser Scanning Microscopy ◽  
Subsequent Growth ◽  
Cross Bridges ◽  
Human Infections ◽  
Chemical Linkage

ABSTRACT Surface proteins of Staphylococcus aureus fulfill many important roles during the pathogenesis of human infections and are anchored to the cell wall envelope by sortases. Although the chemical linkage of proteins to cell wall cross bridges is known, the mechanisms whereby polypeptides are distributed on the staphylococcal surface have not been revealed. We show here that protein A, the ligand of immunoglobulin, is unevenly distributed over the staphylococcal surface. Upon removal with trypsin, newly synthesized polypeptide is deposited at two to four discrete foci. During subsequent growth, protein A appears to be slowly distributed from these sites. When viewed through multiple focal planes by laser scanning microscopy, protein A foci are arranged in a circle surrounding the bacterial cell. This pattern of distribution requires the LPXTG sorting signal of protein A as well as sortase A, the transpeptidase that anchors polypeptides to cell wall cross bridges. A model is presented whereby protein A deposition at discrete sites coupled with cell wall synthesis enables distribution of protein A on the staphylococcal surface.

scholarly journals Inhibition of the Autolytic System by Vancomycin Causes Mimicry of Vancomycin-Intermediate Staphylococcus aureus-Type Resistance, Cell Concentration Dependence of the MIC, and Antibiotic Tolerance in Vancomycin-Susceptible S. aureus

2006 ◽  
Vol 50 (2) ◽  
pp. 527-533 ◽  
Author(s):  
Krzysztof Sieradzki ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Separation ◽  
Cell Concentration ◽  
Active Form ◽  
Normal Growth ◽  
Biologically Active ◽  
Bacterial Surface ◽  
Gradual Disappearance ◽  
Treated Culture

ABSTRACT Treatment of the fully vancomycin-susceptible Staphylococcus aureus strain COL with subinhibitory concentrations of vancomycin allowed its continued growth but generated a phenotype reminiscent of some S. aureus isolates with vancomycin-intermediate S. aureus (VISA)-type resistance: the bacteria grew in multicellular clusters; electron microscopy showed inhibition of cell separation and accumulation of amorphous cell wall-like material at the bacterial surface. Titration of free vancomycin showed a gradual disappearance of the drug from the medium, which—eventually—coincided with an increase in the growth rate, burst in viable titer, and dispersal of cellular clusters. Addition of inhibitory concentrations of vancomycin to the same strain at a higher cell concentration caused a very different—antibiotic-tolerant—response: an immediate halt in growth, followed by a prolonged lag, during which there was neither a loss of viable titer or optical density nor a change in cell morphology but a gradual removal of vancomycin from the medium to the cell wall of the bacterium, from which the antibiotic could be recovered in a biologically active form. Eventually, the drug-treated culture resumed normal growth. The transient appearance of both the VISA phenotype and vancomycin tolerance could be traced to the inhibition of the autolytic system of the bacterium by vancomycin molecules attached to the cell wall, blocking the access of a staphylococcal murein hydrolase(s) to its cell wall substrate.

scholarly journals A short sequence within subdomain N1 of region A of the Staphylococcus aureus MSCRAMM clumping factor A is required for export and surface display

Microbiology ◽  
2014 ◽  
Vol 160 (4) ◽  
pp. 659-670 ◽  
Author(s):  
Niamh McCormack ◽  
Timothy J. Foster ◽  
Joan A. Geoghegan
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cytoplasmic Membrane ◽  
Signal Sequence ◽  
Surface Display ◽  
Surface Protein ◽  
Covalent Attachment ◽  
Bacterial Surface ◽  
Fibrinogen Binding ◽  
Fibronectin Binding

Clumping factor A (ClfA) is the archetypal fibrinogen-binding surface protein of Staphylococcus aureus and a member of the microbial surface component recognizing adhesive matrix molecules (MSCRAMM) family. An N-terminal signal sequence directs export of the MSCRAMM by the Sec pathway and the C-terminal cell wall-anchoring domain allows covalent attachment of ClfA to peptidoglycan by sortase. Region A of ClfA comprises three independently folded subdomains N1, N2 and N3. Subdomains N2N3 comprise IgG-like folds and promote fibrinogen binding. Nothing is known about the structure or function of subdomain N1. Here we demonstrate an unexpected role for N1 in the export and surface localization of ClfA. Attempted expression of a ClfA variant lacking subdomain N1 resulted in impaired growth of S. aureus and accumulation of ClfA protein in the cytoplasm and cytoplasmic membrane. The presence of residues 211–228 of N1 was required to allow display of ClfA on the bacterial surface. The importance of this region was confirmed when a ClfA variant lacking residues 211–220 was also mislocalized to the cytoplasm and cytoplasmic membrane. However, these residues were not required for export of ClfA lacking the Ser-Asp repeats that link region A to the wall-anchoring domain. Similarly, subdomain N1 of a related MSCRAMM fibronectin-binding protein B was required for export and surface display of the full-length protein, but not a derivative lacking fibronectin-binding repeats. In summary, we demonstrate that residues in the N1 subdomain are required for export and cell wall localization of S. aureus MSCRAMM proteins.

scholarly journals The iron-regulated surface proteins IsdA,IsdB, and IsdH are not required for heme iron utilization in Staphylococcus aureus

2012 ◽  
Vol 329 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Alexander F. Hurd ◽  
Jorge Garcia-Lara ◽  
Yvonne Rauter ◽  
Michaël Cartron ◽  
Ramlan Mohamed ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Heme Iron ◽  
Surface Proteins ◽  
Iron Utilization

scholarly journals Staphylococcus aureus FepA and FepB Proteins Drive Heme Iron Utilization in Escherichia coli

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e56529 ◽  
Author(s):  
Evelyne Turlin ◽  
Michel Débarbouillé ◽  
Katarzyna Augustyniak ◽  
Anne-Marie Gilles ◽  
Cécile Wandersman
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Heme Iron ◽  
Iron Utilization

scholarly journals Subcellular Localization of the Staphylococcus aureus Heme Iron Transport Components IsdA and IsdB

2009 ◽  
Vol 77 (7) ◽  
pp. 2624-2634 ◽  
Author(s):  
Gleb Pishchany ◽  
Susan E. Dickey ◽  
Eric P. Skaar
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Iron Transport ◽  
Iron Acquisition ◽  
Iron Status ◽  
Heme Iron ◽  
Global Public Health ◽  
Iron Starvation ◽  
Discrete Location ◽  
Surface Receptor

ABSTRACT Staphylococcus aureus is a human pathogen that represents a tremendous threat to global public health. An important aspect of S. aureus pathogenicity is the ability to acquire iron from its host during infection. In vertebrates, iron is sequestered predominantly within heme, the majority of which is bound by hemoglobin. To acquire iron, S. aureus binds hemoglobin, removes heme, and transports it into the cytoplasm, where heme is degraded. This process is carried out by the iron-regulated surface determinant system (Isd); however, the mechanism by which hemoglobin recognition occurs is not completely understood. Here we report that the surface receptor components of the Isd system, IsdA and IsdB, physically interact with each other and are anchored to a discrete location within the cell wall. This organized localization pattern is dependent upon the iron status of the bacterium. Furthermore, we have found that hemoglobin colocalizes with IsdB at discrete sites within the cell wall. Virulence studies revealed that IsdB is required for the efficient colonization of the heart and that IsdB is differentially expressed within infected organs, suggesting that S. aureus experiences various degrees of iron starvation depending on the site of infection. These findings significantly expand our understanding of hemoglobin iron acquisition and demonstrate an orchestrated pattern of regulation and localization for the S. aureus heme iron acquisition system.

scholarly journals Rhodomyrtone Accumulates in Bacterial Cell Wall and Cell Membrane and Inhibits the Synthesis of Multiple Cellular Macromolecules in Epidemic Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 543
Author(s):  
Ozioma F. Nwabor ◽  
Sukanlaya Leejae ◽  
Supayang P. Voravuthikunchai
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Membrane ◽  
Bacterial Cell ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Options ◽  
Bacterial Cell Wall ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Inhibitor Compounds

As the burden of antibacterial resistance worsens and treatment options become narrower, rhodomyrtone—a novel natural antibiotic agent with a new antibacterial mechanism—could replace existing antibiotics for the treatment of infections caused by multi-drug resistant Gram-positive bacteria. In this study, rhodomyrtone was detected within the cell by means of an easy an inexpensive method. The antibacterial effects of rhodomyrtone were investigated on epidemic methicillin-resistant Staphylococcus aureus. Thin-layer chromatography demonstrated the entrapment and accumulation of rhodomyrtone within the bacterial cell wall and cell membrane. The incorporation of radiolabelled precursors revealed that rhodomyrtone inhibited the synthesis of macromolecules including DNA, RNA, proteins, the cell wall, and lipids. Following the treatment with rhodomyrtone at MIC (0.5–1 µg/mL), the synthesis of all macromolecules was significantly inhibited (p ≤ 0.05) after 4 h. Inhibition of macromolecule synthesis was demonstrated after 30 min at a higher concentration of rhodomyrtone (4× MIC), comparable to standard inhibitor compounds. In contrast, rhodomyrtone did not affect lipase activity in staphylococci—both epidemic methicillin-resistant S. aureus and S. aureus ATCC 29213. Interfering with the synthesis of multiple macromolecules is thought to be one of the antibacterial mechanisms of rhodomyrtone.

Sign in / Sign up

Export Citation Format

Share Document