Miniature on-chip detection of unpurified methicillin-resistant Staphylococcus aureus (MRSA) DNA using real-time PCR.

This paper evaluates the ability to detect three forms of methicillin-resistant Staphylococcus aureus (MRSA) in a microfluidic system. The MRSA was prepared off-chip by varying levels of sample preparation: one containing purified genomic DNA, another containing the supernatant of a crude preparation using simple reagents, and a third through boiled culture preparation without any additional reagents. Polydimethylsiloxane (PDMS) microfluidic chips were fabricated using soft lithography and then bonded to a 22mmx22mmx0.

Staphylococcus aureus fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia.

The tremendous success of Staphylococcus aureus as a pathogen is due to the controlled expression of a diverse array of virulence factors. The effects of host environments on the expression of virulence factors and the mechanisms by which S. aureus adapts to colonize distinct host tissues are largely unknown.

Acinetobacter baumannii increases tolerance to antibiotics in response to monovalent cations.

Acinetobacter baumannii is well adapted to the hospital environment, where infections caused by this organism are associated with significant morbidity and mortality. Genetic determinants of antimicrobial resistance have been described extensively, yet the mechanisms by which A. baumannii regulates antibiotic resistance have not been defined.

Nutritional immunity beyond iron: a role for manganese and zinc.

Vertebrates sequester iron from invading pathogens, and conversely, pathogens express a variety of factors to steal iron from the host. Recent work has demonstrated that in addition to iron, vertebrates sequester zinc and manganese both intracellularly and extracellularly to protect against infection. Intracellularly, vertebrates utilize the ZIP/ZnT families of transporters to manipulate zinc levels, as well as Nramp1 to manipulate manganese levels.

Assessing the contribution of heme-iron acquisition to Staphylococcus aureus pneumonia using computed tomography.

Background: S. aureus acquires heme-iron using the iron regulated surface determinant (Isd) system and the heme transport system (Hts) with both systems showing critical importance in systemic models of infection. The contribution of heme-iron acquisition to staphylococcal pneumonia has not yet been elucidated.

The heme sensor system of Staphylococcus aureus.

The important human pathogen Staphylococcus aureus is able to satisfy its nutrient iron requirement by acquiring heme from host hemoglobin in the context of infection. However, heme acquisition exposes S. aureus to heme toxicity.

A precious metal heist.

Nearly all bacterial pathogens require iron to successfully infect their vertebrate hosts. The host molecule lipocalin-2 exploits this by sequestering bacterial siderophores as a mechanism of protection against infection. Raffatellu et al.

Bacillus anthracis HssRS signalling to HrtAB regulates haem resistance during infection.

Bacillus anthracis proliferates to high levels within vertebrate tissues during the pathogenesis of anthrax. This growth is facilitated by the acquisition of nutrient iron from host haem. However, haem acquisition can lead to the accumulation of toxic amounts of haem within B.

Subcellular localization of the Staphylococcus aureus heme iron transport components IsdA and IsdB.

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.

Ruffling of metalloporphyrins bound to IsdG and IsdI, two heme-degrading enzymes in Staphylococcus aureus.

IsdG and IsdI are paralogous proteins that are intracellular components of a complex heme uptake system in Staphylococcus aureus. IsdG and IsdI were shown previously to reductively degrade hemin. Crystal structures of the apoproteins show that these proteins belong to a newly identified heme degradation family distinct from canonical eukaryotic and prokaryotic heme oxygenases.

Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem.

Iron acquisition is a vital process for most pathogenic bacteria, as iron is a limiting nutrient during infection. Staphylococcus aureus, an increasingly important pathogen, acquires iron from host haem via elaboration of the iron-regulated surface determinant system (Isd). IsdG and IsdI are haem oxygenases that have been proposed to degrade exogenous haem in the bacterial cytoplasm as a mechanism to liberate free iron for use as a nutrient source.

Staphylococcus aureus HrtA is an ATPase required for protection against heme toxicity and prevention of a transcriptional heme stress response.

During systemic infection, Staphylococcus aureus acquires nutrient iron from heme, the cofactor of vertebrate myoglobin and hemoglobin. Upon exposure to heme, S. aureus up-regulates the expression of the heme-regulated transporter, HrtAB.

Metal chelation and inhibition of bacterial growth in tissue abscesses.

Bacterial infection often results in the formation of tissue abscesses, which represent the primary site of interaction between invading bacteria and the innate immune system. We identify the host protein calprotectin as a neutrophil-dependent factor expressed inside Staphylococcus aureus abscesses. Neutrophil-derived calprotectin inhibited S.

Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus.

In recent years, there has been a dramatic increase in the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. MW2 (pulsed-field type USA400), the prototype CA-MRSA strain, is highly virulent and has enhanced ability to evade killing by neutrophils. Although progress has been made, the molecular basis for enhanced virulence of CA-MRSA remains incompletely defined.

A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence.

Staphylococcus aureus, a bacterium responsible for tremendous morbidity and mortality, exists as a harmless commensal in approximately 25% of humans. Identifying the molecular machinery activated upon infection is central to understanding staphylococcal pathogenesis. We describe the heme sensor system (HssRS) that responds to heme exposure and activates expression of the heme-regulated transporter (HrtAB).

Signaling and DNA-binding activities of the Staphylococcus aureus HssR-HssS two-component system required for heme sensing.

For the important human pathogen Staphylococcus aureus, host heme is a vital source of nutrient iron during infection. Paradoxically, heme is also toxic at high concentrations and is capable of killing S. aureus.

Intracellular metalloporphyrin metabolism in Staphylococcus aureus.

The bacterial pathogen Staphylococcus aureus is responsible for a significant amount of human morbidity and mortality, and the ability of S. aureus to cause disease is absolutely dependent on the acquisition of iron from the host. The most abundant iron source to invading staphylococci is in the form of the porphyrin heme.

Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron utilization.

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.

Staphylococcus aureus redirects central metabolism to increase iron availability.

Staphylococcus aureus pathogenesis is significantly influenced by the iron status of the host. However, the regulatory impact of host iron sources on S. aureus gene expression remains unknown.

Bacillus anthracis IsdG, a heme-degrading monooxygenase.

Bacillus anthracis, the causative agent of anthrax, utilizes hemin and hemoglobin for growth in culture, suggesting that these host molecules serve as sources for the nutrient iron during bacterial infection. Bioinformatic analyses of the B. anthracis genome revealed genes with similarity to the iron-regulated surface determinant (isd) system responsible for heme uptake in Staphylococcus aureus.

Analysis of the Piv recombinase-related gene family of Neisseria gonorrhoeae.

Neisseria gonorrhoeae (the gonococcus) is an obligate human pathogen and the causative agent of the disease gonorrhea. The gonococcal pilus undergoes antigenic variation through high-frequency recombination events between unexpressed pilS silent copies and the pilin expression locus pilE. The machinery involved in pilin antigenic variation identified to date is composed primarily of genes involved in homologous recombination.

Staphylococcus aureus IsdG and IsdI, heme-degrading enzymes with structural similarity to monooxygenases.

Heme-degrading enzymes are involved in human diseases ranging from stroke, cancer, and multiple sclerosis to infectious diseases such as malaria, diphtheria, and meningitis. All mammalian and microbial enzymes identified to date are members of the heme oxygenase superfamily and assume similar monomeric structures with an all alpha-helical fold. Here we describe the crystal structures of IsdG and IsdI, two heme-degrading enzymes from Staphylococcus aureus.

Iron-source preference of Staphylococcus aureus infections.

Although bacteria use different iron compounds in vitGro, the possibility that microbes distinguish between these iron sources during infection has hitherto not been examined. We applied stable isotope labeling to detect source-specific iron by mass spectrometry and show that Staphylococcus aureus preferentially imports heme iron over transferrin iron. By combining this approach with computational genome analysis, we identified hts (heme transport system), a gene cluster that promotes preferred heme iron import by S.

Iron-regulated surface determinants (Isd) of Staphylococcus aureus: stealing iron from heme.

Cell-wall sorted proteins of the Staphylococcus aureus iron-regulated surface determinant system bind human hemoproteins, remove the heme molecule, and transport heme through the cell wall and plasma membrane for accumulation in the bacterial cytoplasm. Once inside the cell, the porphyrin ring of heme is degraded by heme degrading monooxygenases, leading to the formation of free iron for use by the bacterium as a nutrient source.

IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus.

Staphylococcus aureus requires iron for growth and utilizes heme as a source of iron during infection. Staphylococcal surface proteins capture hemoglobin, release heme from hemoglobin and transport this compound across the cell wall envelope and plasma membrane into the bacterial cytoplasm. Here we show that Staphylococcus aureus isdG and isdI encode cytoplasmic proteins with heme binding properties.