A battle for iron: host sequestration and Staphylococcus aureus acquisition

In the paper

“upon breaching this initial site of colonization, S. aureus has the capacity to infect nearly every tissue in the human body.”

What the sources say

• Not checked yetcites [2] David, 2010, Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic, Clin. Microbiol. Rev. source

In the paper

“To combat infection vertebrates have evolved sophisticated iron sequestration systems against which, pathogenic bacteria have concomitantly evolved equally elaborate iron acquisition mechanisms.”

In the paper

“S. aureus is the most frequent cause of nosocomial infections in the United States, with the percentage of infections caused by methicillin resistant Staphylococcus aureus (MRSA) growing precipitously [3].”

What the sources say

• Not checked yetcites [3] Todd, 2006, Beyond MRSA: VISA and VRSA: what will ward off these pathogens in health care facilities?, Am. J. Nurs. source

In the paper

“Staphylococcus aureus is a Gram-positive coccoid bacterium that innocuously colonizes the anterior nares of approximately 30% of the human population [1].”

What the sources say

• Not checked yetcites [1] Kuehnert, 2006, Prevalence of Staphylococcus aureus nasal colonization in the United States, 2001-2002, J. Infect. Dis. source

In the paper

“Consequently most living organisms, including pathogenic bacteria, require iron to survive and replicate.”

In the paper

“S. aureus can cause a spectrum of ailments ranging from superficial wound infections to more severe diseases such as septicemia, toxic shock syndrome and endocarditis [2].”

What the sources say

• Not checked yetcites [2] David, 2010, Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic, Clin. Microbiol. Rev. source

In the paper

“Iron overload associated with thalassaemia patients has been implicated as a cause for the increased infections within this population [18].”

What the sources say

• Not checked yetcites [18] Rahav, 2006, Severe infections in thalassaemic patients: prevalence and predisposing factors, Br. J. Haematol. source

In the paper

“iron overload compromises the efficacy of phagocytic cells by decreasing their chemotactic capabilities and increasing the ease with which engulfed bacteria can proliferate intracellularly within macrophages [15].”

What the sources say

• Not checked yetcites [15] Khan, 2007, Association of hemochromatosis with infectious diseases: expanding spectrum, Int. J. Infect. Dis. source

In the paper

“Hemopexin binds free heme and delivers it to the liver where it can be taken up by hepatic parenchymal cells through receptor-mediated endocytosis (Fig. 1) [13].”

What the sources say

• Not checked yetcites [13] Tolosano, 2010, Heme scavenging and the other facets of hemopexin, Antioxid. Redox Sign. source

In the paper

“either iron starvation or fur inactivation leads to a significant reduction in the abundance of numerous enzymes of the TCA cycle and a simultaneous increase in the abundance of proteins within the glycolytic pathway [19].”

What the sources say

• Not checked yetcites [19] Friedman, 2006, Staphylococcus aureus redirects central metabolism to increase iron availability, PLoS Pathog. source

In the paper

“Therefore, shifting to fermentative metabolism benefits iron starved S. aureus by increasing lactate production which decreases the surrounding pH and increases the local levels of free iron.”

In the paper

“This increase in transferrin saturation decreases the bacteriostatic nature of serum as it is easier for pathogens to attain iron from transferrin [15]. Consequently HH is associated with an increased risk of both bacterial and viral infections [15].”

What the sources say

• Not checked yetcites [15] Khan, 2007, Association of hemochromatosis with infectious diseases: expanding spectrum, Int. J. Infect. Dis. source

In the paper

“the S. aureus hemoglobin receptor IsdB binds human hemoglobin more efficiently than hemoglobin from other animal species [47]. In fact the KD of the interaction between recombinant IsdB and human hemoglobin is 5.5 × 10−8 as compared to a KD of 9.8 × 10−7 for the interaction between IsdB and mouse hemoglobin.”

What the sources say

• Not checked yetcites [47] Pishchany, 2010, Specificity for human hemoglobin enhances Staphylococcus aureus infection, Cell Host Microbe source

In the paper

“Iron overload occurs in β thalassaemia due to the increased iron demand caused by dysfunctional erythropoiesis [16].”

What the sources say

• Not checked yetcites [16] Gardenghi, 2010, Hepcidin and Hfe in iron overload in beta-thalassemia, Ann. N. Y. Acad. Sci. source

In the paper

“both Δfur mutants and wildtype S. aureus grown in iron-deplete media produce markedly more lactate than wildtype bacteria grown in iron-replete conditions, leading to a decrease in the local pH [19].”

What the sources say

• Not checked yetcites [19] Friedman, 2006, Staphylococcus aureus redirects central metabolism to increase iron availability, PLoS Pathog. source

In the paper

“Transgenic mice that express human hemoglobin are more susceptible to S. aureus infection than wildtype mice demonstrating the pathophysiological relevance of these findings.”

What the sources say

• Not checked yetcites [47] Pishchany, 2010, Specificity for human hemoglobin enhances Staphylococcus aureus infection, Cell Host Microbe source

In the paper

“The overwhelming majority of iron within humans is found in the form of heme; a tetrapyrrole ring with a coordinated iron center. Heme is often bound by hemoproteins, the most abundant of which is hemoglobin.”

In the paper

“Infections are among the major causes of mortality in patients with thalassaemia (12–46%) along with cardiovascular disease and liver failure [18].”

What the sources say

• Not checked yetcites [18] Rahav, 2006, Severe infections in thalassaemic patients: prevalence and predisposing factors, Br. J. Haematol. source

In the paper

“Upon binding to ferroportin, hepcidin causes ferroportin endocytosis and subsequent proteolytic degradation decreasing the release of iron into the plasma [12].”

What the sources say

• Not checked yetcites [12] Ganz, 2011, Hepcidin and iron regulation, 10 years later, Blood source

In the paper

“S. aureus binds haptoglobin-hemoglobin complexes in vitro, suggesting that this protein complex is exploited as a source of nutrient iron [8].”

What the sources say

• Not checked yetcites [8] Dryla, 2003, Identification of a novel iron regulated staphylococcal surface protein with haptoglobin-haemoglobin binding activity, Mol. Microbiol. source

In the paper

“One such system is the iron regulated surface determinant (Isd) system which includes the cell wall anchored heme binding proteins (IsdA and IsdC), a hemoglobin receptor (IsdB), a hemoglobin-haptoglobin receptor (IsdH), a membrane transporter (IsdEF), and two cytoplasmic heme oxygenases (IsdG and IsdI) [22].”

What the sources say

• Not checked yetcites [22] Grigg, 2010, Structural biology of heme binding in the Staphylococcus aureus Isd system, J. Inorg. Biochem. source

In the paper

“As an acute-phase protein, hemopexin concentrations increase during inflammation and are regulated by the cytokines IL-6, IL-11 IL-1β, leukemia inhibitory factor, and tumor necrosis factor (TNF)-α [14]. The increase in hemopexin levels during infection counteracts the hemolytic activity of pathogenic bacteria.”

What the sources say

• Not checked yetcites [14] Tolosano, 2002, Hemopexin: structure, function, and regulation, DNA Cell Biol. source

In the paper

“β Thalassaemia is an inherited disorder affecting hemoglobin synthesis. Mutations within the β globin gene cause diverse degrees of defective β chain production, ineffective erythropoiesis, improper α/βchain ratios, iron overload, and a range of anemia [16].”

What the sources say

• Not checked yetcites [16] Gardenghi, 2010, Hepcidin and Hfe in iron overload in beta-thalassemia, Ann. N. Y. Acad. Sci. source

In the paper

“Iron levels are also limited in lymph and mucosal secretions through lactoferrin, which quickly binds all free iron. Additionally, lactoferrin is a major component within phagocytes, ensuring that engulfed pathogens have limited access to intracellular iron.”

What the sources say

• Not checked yetcites [5] Bullen, 2005, Iron and infection: the heart of the matter, FEMS Immunol, Med. Microbiol.

In the paper

“In the presence of iron, Fur binds a consensus DNA sequence referred to as a fur box located upstream of the transcriptional start site of iron-regulated genes. The binding of Fur to the fur box typically inhibits the transcription of target genes. During conditions of iron starvation, Fur repression is alleviated and transcription is activated.”

What the sources say

• Not checked yetcites [19] Friedman, 2006, Staphylococcus aureus redirects central metabolism to increase iron availability, PLoS Pathog. source

In the paper

“greater than 90% of iron within the human body is located intracellularly making it inaccessible to extracellular pathogens unless mechanisms are employed to liberate these rich sources of nutrient iron.”

In the paper

“In a murine model of pneumonia, S. aureus fur mutants induce greater neutrophil recruitment despite a decreased ability to colonize and proliferate within the lung. Interestingly, S. aureus fur mutants are still able to proliferate in the lungs of neutropenic mice suggesting that Fur controls an anti-neutrophil response that protects S. aureus during infection of the vertebrate lung [21].”

What the sources say

• Not checked yetcites [21] Torres, 2010, Staphylococcus aureus Fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia, Infect. Immun. source

In the paper

“within the United States S. aureus is responsible for more deaths than HIV [4].”

What the sources say

• Not checked yetcites [4] CDC, 2007, HIV/AIDS Surveill. Rep.

In the paper

“Iron is required by nearly all living organisms and S. aureus is no exception.”

In the paper

“induction of IL-6 production and LPS-mediated TLR4 signaling both cause increases in circulating hepcidin (Fig. 1) [12]. Inflammation-induced increases in hepcidin represent a hypoferremic response to infection which allows the host to respond to bacterial assault by further reducing available iron and preventing bacterial replication [12].”

What the sources say

• Not checked yetcites [12] Ganz, 2011, Hepcidin and iron regulation, 10 years later, Blood source

In the paper

“The N-end rule relates the half-life of a protein to the N-terminal amino acid while the SsrA tag is an eleven amino acid tag that is added to the carboxy-terminus of incompletely translated proteins relegating them to degradation [54–55].”

What the sources say

• Not checked yetcites [55] Keiler, 1996, Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA, Science source

In the paper

“While both enzymes bind and degrade heme they are differentially regulated indicating a possible rationale for encoding two paralogous heme oxygenases [46, 51].”

What the sources say

• Not checked yetcites [46] Skaar, 2004, IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus, J. Biol. Chem. source
• Not checked yetcites [51] Reniere, 2008, Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem, Mol. Microbiol. source

In the paper

“This indicates that structural differences may exist in S. lugdunensis IsdG that prevent it from being targeted for degradation.”

In the paper

“Although S. lugdunensis IsdG and S. aureus IsdG are 68% identical at the amino acid level the S. lugdunensis enzyme is stable in the absence of heme.”

What the sources say

• Not checked yetcites [50] Haley, 2011, Staphylococcus lugdunensis IsdG liberates iron from host heme, J. Bacteriol. source

In the paper

“This fact is underscored by the antimicrobial activity of acyldepsipeptides which render cytoplasmic proteases constitutively active [52].”

What the sources say

• Not checked yetcites [52] Brotz-Oesterhelt, 2005, Dysregulation of bacterial proteolytic machinery by a new class of antibiotics, Nat. Med. source

In the paper

“Different host tissues likely have varying amounts of accessible iron and therefore S. aureus may vary in its dependency on iron from heme.”

In the paper

“S. lugdunensis encodes a single IsdG-family heme oxygenase which is iron regulated.”

What the sources say

• Not checked yetcites [50] Haley, 2011, Staphylococcus lugdunensis IsdG liberates iron from host heme, J. Bacteriol. source

In the paper

“IsdG-family heme oxygenases have been characterized in S. lugdunensis, Bacillus anthracis, Bradyrhizobium japonicum, Brucella melitensis, and Mycobacterium tuberculosis [46, 50, 56–58].”

What the sources say

• Not checked yetcites [46] Skaar, 2004, IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus, J. Biol. Chem. source
• Not checked yetcites [50] Haley, 2011, Staphylococcus lugdunensis IsdG liberates iron from host heme, J. Bacteriol. source
• Not checked yetcites [56] Chim, 2010, Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis, J. Mol. Biol. source
• Not checked yetcites [57] Puri, 2006, The hmuQ and hmuD genes from Bradyrhizobium japonicum encode heme-degrading enzymes, J. Bacteriol. source
• Not checked yetcites [58] Skaar, 2006, Bacillus anthracis IsdG, a heme-degrading monooxygenase, J. Bacteriol. source

In the paper

“This unusual diheme conformation does not affect the heme degrading capabilities of MhuD, however, as the product of MhuD heme degradation has not been determined; it is unclear if the diheme active site degrades heme to staphylobilin.”

What the sources say

• Not checked yetcites [56] Chim, 2010, Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis, J. Mol. Biol. source

In the paper

“Taken together these data suggest that while both IsdG and IsdI are required for full virulence in S. aureus, and these enzymes are not functionally redundant during vertebrate infection [51].”

What the sources say

• Not checked yetcites [51] Reniere, 2008, Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem, Mol. Microbiol. source

In the paper

“While IsdG orthologs from each of these bacteria have been shown to bind and degrade heme, differences do exist.”

What the sources say

• Not checked yetcites [46] Skaar, 2004, IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus, J. Biol. Chem. source
• Not checked yetcites [50] Haley, 2011, Staphylococcus lugdunensis IsdG liberates iron from host heme, J. Bacteriol. source
• Not checked yetcites [56] Chim, 2010, Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis, J. Mol. Biol. source
• Not checked yetcites [57] Puri, 2006, The hmuQ and hmuD genes from Bradyrhizobium japonicum encode heme-degrading enzymes, J. Bacteriol. source
• Not checked yetcites [58] Skaar, 2006, Bacillus anthracis IsdG, a heme-degrading monooxygenase, J. Bacteriol. source

In the paper

“Both isdG and isdI transcript levels increase in iron-deplete conditions and are subjected to Fur-mediated regulation [51].”

What the sources say

• Not checked yetcites [51] Reniere, 2008, Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem, Mol. Microbiol. source

In the paper

“The targeted degradation of IsdG in the absence of heme does not occur through either the N-end rule or the SsrA tag as neither termini are required for proteolytic recognition [53].”

What the sources say

• Not checked yetcites [53] Reniere, 2011, The flexible loop of Staphylococcus aureus IsdG is required for its degradation in the absence of heme, Biochemistry source

In the paper

“Currently, the most well characterized mechanisms for substrate recognition by bacterial proteases are the N-end rule and the SsrA tag.”

What the sources say

• Not checked yetcites [54] Varshavsky, 1996, The N-end rule: functions, mysteries, uses, Proc. Natl. Acad. Sci. U S A source
• Not checked yetcites [55] Keiler, 1996, Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA, Science source

In the paper

“The N-end rule relates the half-life of a protein to the N-terminal amino acid while the SsrA tag is an eleven amino acid tag that is added to the carboxy-terminus of incompletely translated proteins relegating them to degradation [54–55].”

What the sources say

• Not checked yetcites [54] Varshavsky, 1996, The N-end rule: functions, mysteries, uses, Proc. Natl. Acad. Sci. U S A source

In the paper

“Each MhuD monomer binds two heme molecules with the porphyrin rings stacked 3.45 Å apart [56].”

What the sources say

• Not checked yetcites [56] Chim, 2010, Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis, J. Mol. Biol. source

In the paper

“Furthermore, none of the known staphylococcal proteases are responsible for the degradation of apo-IsdG, suggesting that S. aureus encodes an as-yet unidentified protease involved in protein turnover [53].”

What the sources say

• Not checked yetcites [53] Reniere, 2011, The flexible loop of Staphylococcus aureus IsdG is required for its degradation in the absence of heme, Biochemistry source

In the paper

“In fact, some of these IsdG-containing bacteria are considered extremophiles, occupying some of the earth's harshest environments.”

What the sources say

• Not checked yetcites [50] Haley, 2011, Staphylococcus lugdunensis IsdG liberates iron from host heme, J. Bacteriol. source

In the paper

“Interestingly, while both S. aureus ΔisdG and S. aureus ΔisdI are attenuated for virulence in murine hearts, only S. aureus ΔisdG is attenuated for virulence within murine kidneys.”

What the sources say

• Not checked yetcites [51] Reniere, 2008, Staphylococcus aureus haem oxygenases are differentially regulated by iron and haem, Mol. Microbiol. source

In the paper

“Together this suggests that staphyloferrin A contributes to staphylococcal transferrin-iron acquisition but is not the predominant means by which S. aureus procures iron from transferrin.”

In the paper

“Orthologous HrtAB systems have been identified in a number of species including L. monocytogenes, Bacillus thuringiensis,Bacillus cereus, Lactococcus lactis, Streptococcus agalactiae and S. epidermidis indicating that alleviation of heme toxicity is a common obstacle faced by many Gram positive bacteria [63, 66–67].”

What the sources say

• Not checked yetcites [63] Torres, 2007, A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence, Cell Host Microbe source
• Not checked yetcites [66] Pedersen, 2008, Impact of aeration and heme-activated respiration on Lactococcus lactis gene expression: identification of a heme-responsive operon, J. Bacteriol. source
• Not checked yetcites [67] Fernandez, 2010, Two coregulated efflux transporters modulate intracellular heme and protoporphyrin IX availability in Streptococcus agalactiae, PLoS Pathog. source

In the paper

“Both HssR and HssS are required for heme adaptation and inactivating either hssR or hssS results in hyper-susceptibility to the lethal effects of heme.”

What the sources say

• Not checked yetcites [64] Stauff, 2007, Signaling and DNA-binding activities of the Staphylococcus aureus HssR-HssS two-component system required for heme sensing, J. Biol. Chem. source

In the paper

“Like NreBC, HssRS is a paradigmatic two component system consisting of a histidine kinase (HssS) and a response regulator (HssR) [64].”

What the sources say

• Not checked yetcites [64] Stauff, 2007, Signaling and DNA-binding activities of the Staphylococcus aureus HssR-HssS two-component system required for heme sensing, J. Biol. Chem. source

In the paper

“Siderophore production is Fur-regulated and consequently increases when the bacteria experience iron stress [19, 60].”

What the sources say

• Not checked yetcites [19] Friedman, 2006, Staphylococcus aureus redirects central metabolism to increase iron availability, PLoS Pathog. source
• Not checked yetcites [60] Lindsay, 1994, Staphylococcal iron requirements, siderophore production, and iron-regulated protein expression, Infect. Immun. source

In the paper

“The hemoglobin binding protein IsdB plays a pivotal role during infection and is surface exposed establishing this protein as a viable vaccine candidate [47].”

What the sources say

• Not checked yetcites [47] Pishchany, 2010, Specificity for human hemoglobin enhances Staphylococcus aureus infection, Cell Host Microbe source

In the paper

“The protective effect of the vaccine is likely due to the production of anti-IsdB antibodies as mice with higher anti-IsdB titers had a greater probability of surviving than those with low anti-IsdB titers [68].”

What the sources say

• Not checked yetcites [68] Kuklin, 2006, A novel Staphylococcus aureus vaccine: iron surface determinant B induces rapid antibody responses in rhesus macaques and specific increased survival in a murine S. aureus sepsis model, Infect. Immun. source

In the paper

“Upon binding iron, both staphyloferrin A and staphyloferrin B are transported into the cytoplasm through the ABC transporters HtsABC and the staphylococcal iron regulated transporter (SirABC), respectively [61].”

What the sources say

• Not checked yetcites [61] Beasley, 2010, Siderophore-mediated iron acquisition in the staphylococci, J. Inorg. Biochem. source

In the paper

“The HrtAB system is comprised of an ATPase (HrtA) and a permease (HrtB).”

In the paper

“Within these nodules B. japonicum acquires heme from leghemoglobin, a plant hemoglobin with structural properties similar to animal hemoglobins that can comprise up to 30% of the total soluble protein within plant nodules [59].”

What the sources say

• Not checked yetcites [59] Noya, 1997, Heme compounds as iron sources for nonpathogenic Rhizobium bacteria, J. Bacteriol. source

In the paper

“A S. aureus sbn mutant strain has impaired growth in serum, but achieves wildtype cell densities after extensive incubation, presumably due to the production of staphyloferrin A [62].”

What the sources say

• Not checked yetcites [62] Beasley, 2009, Characterization of staphyloferrin A biosynthetic and transport mutants in Staphylococcus aureus, Mol. Microbiol. source

In the paper

“Since this ABC-type transporter is dramatically increased in response to heme it has been termed the heme regulated transporter (hrtAB) [19].”

What the sources say

• Not checked yetcites [19] Friedman, 2006, Staphylococcus aureus redirects central metabolism to increase iron availability, PLoS Pathog. source

In the paper

“However, in some species of coagulase-negative staphylococci the sfa locus is believed to be constitutively expressed [60, 62].”

What the sources say

• Not checked yetcites [60] Lindsay, 1994, Staphylococcal iron requirements, siderophore production, and iron-regulated protein expression, Infect. Immun. source
• Not checked yetcites [62] Beasley, 2009, Characterization of staphyloferrin A biosynthetic and transport mutants in Staphylococcus aureus, Mol. Microbiol. source

In the paper

“Staphyloferrin B is structurally distinct from staphyloferrin A but like staphyloferrin A is a hydrophilic NIS siderophore.”

What the sources say

• Not checked yetcites [61] Beasley, 2010, Siderophore-mediated iron acquisition in the staphylococci, J. Inorg. Biochem. source

In the paper

“The sfa locus contains four genes, the three gene operon sfaABC and a divergently transcribed sfaD [60, 62].”

What the sources say

• Not checked yetcites [60] Lindsay, 1994, Staphylococcal iron requirements, siderophore production, and iron-regulated protein expression, Infect. Immun. source
• Not checked yetcites [62] Beasley, 2009, Characterization of staphyloferrin A biosynthetic and transport mutants in Staphylococcus aureus, Mol. Microbiol. source

In the paper

“The ATPase activity of HrtA is influenced by many cellular factors including ATP concentrations, temperature, pH, and metal concentrations [65].”

What the sources say

• Not checked yetcites [65] Stauff, 2008, Staphylococcus aureus HrtA is an ATPase required for protection against heme toxicity and prevention of a transcriptional heme stress response, J. Bacteriol. source

In the paper

“Heme exposure leads to the autophosphorylation of HssS which subsequently transphosphorylates the response regulator HssR.”

What the sources say

• Not checked yetcites [64] Stauff, 2007, Signaling and DNA-binding activities of the Staphylococcus aureus HssR-HssS two-component system required for heme sensing, J. Biol. Chem. source

In the paper

“The genes encoding the enzymatic machinery required for staphyloferrin B synthesis lie within the sbn locus which has a consensus fur box within the operator region for the operon [61].”

What the sources say

• Not checked yetcites [61] Beasley, 2010, Siderophore-mediated iron acquisition in the staphylococci, J. Inorg. Biochem. source

In the paper

“Additionally, HtsBC has been found to transport heme into the cytoplasm suggesting that HtsABC may serve as a dual iron/heme transporter [37].”

What the sources say

• Not checked yetcites [37] Skaar, 2004, Iron-source preference of Staphylococcus aureus infections, Science source

In the paper

“S. aureus encodes for two siderophores, staphyloferrin A and staphyloferrin B, and both are synthesized through the NIS pathway and then secreted into the extracellular milieu.”

What the sources say

• Not checked yetcites [61] Beasley, 2010, Siderophore-mediated iron acquisition in the staphylococci, J. Inorg. Biochem. source

In the paper

“To circumvent the iron sequestration of the host, pathogenic bacteria have evolved multi-faceted iron acquisition systems to extract iron from host proteins and gain access to intracellular pools of iron.”

In the paper

“This raises the interesting possibility that antibodies against IsdB provide protection by inhibiting iron acquisition through the Isd system.”

In the paper

“Iron acquisition is a critical determinant in staphylococcal pathogenesis and one that is exploited by vertebrates through nutritional immunity.”

In the paper

“Gram-positive bacteria are typically resistant to complement mediated lysis, therefore host clearance of S. aureus requires opsonophagocytic killing by immune cells [69].”

What the sources say

• Not checked yetcites [69] Kim, 2010, IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge, Vaccine source