staphylococcal protein a


Summary: A protein present in the cell wall of most Staphylococcus aureus strains. The protein selectively binds to the Fc region of human normal and myeloma-derived IMMUNOGLOBULIN G. It elicits antibody activity and may cause hypersensitivity reactions due to histamine release; has also been used as cell surface antigen marker and in the clinical assessment of B lymphocyte function.

Top Publications

  1. Dutta P, Sawoo S, Ray N, Bouloussa O, Sarkar A. Engineering bioactive surfaces with Fischer carbene complex: protein A on self-assembled monolayer for antibody sensing. Bioconjug Chem. 2011;22:1202-9 pubmed publisher
    ..Rabbit IgG could be removed from protein A coated surface by pH adjustment. The regenerated protein A surface was reused three times without loss of activity. ..
  2. Moodley A, Stegger M, Ben Zakour N, Fitzgerald J, Guardabassi L. Tandem repeat sequence analysis of staphylococcal protein A (spa) gene in methicillin-resistant Staphylococcus pseudintermedius. Vet Microbiol. 2009;135:320-6 pubmed publisher
    A putative staphylococcal protein A (spa) gene was discovered in the genome of Staphylococcus pseudintermedius and used for developing a species-specific spa typing protocol. Thirty-one clinical methicillin-resistant S...
  3. Bosch T, de Neeling A, Schouls L, van der Zwaluw K, Kluytmans J, Grundmann H, et al. PFGE diversity within the methicillin-resistant Staphylococcus aureus clonal lineage ST398. BMC Microbiol. 2010;10:40 pubmed publisher
    ..The adjustments in the PFGE protocol using Cfr9I are easy to implement to study the ST398 clonal lineage in laboratories which already have a PFGE facility. ..
  4. Cheng A, Dedent A, Schneewind O, Missiakas D. A play in four acts: Staphylococcus aureus abscess formation. Trends Microbiol. 2011;19:225-32 pubmed publisher
    ..Protein A and coagulases are distinctive virulence attributes for S. aureus, and humoral immune responses specific for these polypeptides provide protection against abscess formation in animal models of staphylococcal disease...
  5. Cheng V, Chan J, Lau E, Yam W, Ho S, Yau M, et al. Studying the transmission dynamics of meticillin-resistant Staphylococcus aureus in Hong Kong using spa typing. J Hosp Infect. 2011;79:206-10 pubmed publisher
    ..Proactive screening of MRSA in patients from elderly care homes and targeted isolation of these patients, especially those carrying spa types with high transmissibility, are important for the control of MRSA in hospitals. ..
  6. Kim H, Kim H, Schneewind O, Missiakas D. Identifying protective antigens of Staphylococcus aureus, a pathogen that suppresses host immune responses. FASEB J. 2011;25:3605-12 pubmed publisher
    ..Genetic vaccinology is particularly useful for microbes that do not elicit natural protective immunity during infection. ..
  7. Sangvik M, Olsen R, Olsen K, Simonsen G, Furberg A, Sollid J. Age- and gender-associated Staphylococcus aureus spa types found among nasal carriers in a general population: the Tromso Staph and Skin Study. J Clin Microbiol. 2011;49:4213-8 pubmed publisher
    ..This may provide valuable clues to the multifactorial mechanisms, among them bacterial factors, involved in nasal colonization with S. aureus. ..
  8. Konrad A, Karlström A, Hober S. Covalent immunoglobulin labeling through a photoactivable synthetic Z domain. Bioconjug Chem. 2011;22:2395-403 pubmed publisher
    ..This feature has been used for directed labeling of immunoglobulins and subsequent use of these in different assays. ..
  9. Reddy P, Shekar A, Kingston J, Sripathy M, Batra H. Evaluation of IgY capture ELISA for sensitive detection of alpha hemolysin of Staphylococcus aureus without staphylococcal protein A interference. J Immunol Methods. 2013;391:31-8 pubmed publisher
    b>Staphylococcal protein A (Spa) secreted by all Staphylococcus aureus strains is the major hindrance in development of specific immunoassays for detecting S...

More Information


  1. Hogwood C, Tait A, Koloteva Levine N, Bracewell D, Smales C. The dynamics of the CHO host cell protein profile during clarification and protein A capture in a platform antibody purification process. Biotechnol Bioeng. 2013;110:240-51 pubmed publisher
  2. Claro T, Widaa A, O Seaghdha M, Miajlovic H, Foster T, O Brien F, et al. Staphylococcus aureus protein A binds to osteoblasts and triggers signals that weaken bone in osteomyelitis. PLoS ONE. 2011;6:e18748 pubmed publisher
    ..This new information may pave the way for the development of new and improved therapeutic agents to treat this disease. ..
  3. Kim H, Emolo C, Dedent A, Falugi F, Missiakas D, Schneewind O. Protein A-specific monoclonal antibodies and prevention of Staphylococcus aureus disease in mice. Infect Immun. 2012;80:3460-70 pubmed publisher
    ..The envelope of S. aureus is decorated with staphylococcal protein A (SpA), which captures the Fc? portion of immunoglobulins to prevent opsonophagocytosis and associates ..
  4. Iijima M, Kadoya H, Hatahira S, Hiramatsu S, Jung G, Martin A, et al. Nanocapsules incorporating IgG Fc-binding domain derived from Staphylococcus aureus protein A for displaying IgGs on immunosensor chips. Biomaterials. 2011;32:1455-64 pubmed publisher
    ..The BNC-coated sensor chip is very stable, and should prove useful for various immunosensor applications due to oriented immobilization of antibodies. ..
  5. Grundmann H, Aanensen D, van den Wijngaard C, Spratt B, Harmsen D, Friedrich A. Geographic distribution of Staphylococcus aureus causing invasive infections in Europe: a molecular-epidemiological analysis. PLoS Med. 2010;7:e1000215 pubmed publisher
  6. Jelsbak L, Hemmingsen L, Donat S, Ohlsen K, Boye K, Westh H, et al. Growth phase-dependent regulation of the global virulence regulator Rot in clinical isolates of Staphylococcus aureus. Int J Med Microbiol. 2010;300:229-36 pubmed publisher
    ..We propose that variation in global regulatory networks contribute considerably to the phenotypic variation observed between S. aureus isolates. ..
  7. Falugi F, Kim H, Missiakas D, Schneewind O. Role of protein A in the evasion of host adaptive immune responses by Staphylococcus aureus. MBio. 2013;4:e00575-13 pubmed publisher
    ..aureus SpA were abolished in µMT mice lacking mature B cells and antibodies. Thus, while wild-type S. aureus escapes host immune surveillance, the spaKKAA variant elicits adaptive responses that protect against recurrent infection...
  8. Fessler A, Kadlec K, Hassel M, Hauschild T, Eidam C, Ehricht R, et al. Characterization of methicillin-resistant Staphylococcus aureus isolates from food and food products of poultry origin in Germany. Appl Environ Microbiol. 2011;77:7151-7 pubmed publisher
  9. Ho P, Chow K, Lo P, Lee K, Lai E. Changes in the epidemiology of methicillin-resistant Staphylococcus aureus associated with spread of the ST45 lineage in Hong Kong. Diagn Microbiol Infect Dis. 2009;64:131-7 pubmed publisher
    ..Two other epidemic clones, EMRSA-16 (ST36/SCCmec II) and CC398 (ST1277/SCCmec V), were detected as sporadic isolates for the first time in Hong Kong. ..
  10. Kim H, Cheng A, Kim H, Missiakas D, Schneewind O. Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice. J Exp Med. 2010;207:1863-70 pubmed publisher
    ..Prior infection with S. aureus is not associated with protective immunity. This phenomenon involves staphylococcal protein A (SpA), an S...
  11. Moiani D, Salvalaglio M, Cavallotti C, Bujacz A, Redzynia I, Bujacz G, et al. Structural characterization of a Protein A mimetic peptide dendrimer bound to human IgG. J Phys Chem B. 2009;113:16268-75 pubmed publisher
    ..The electrostatic and van der Waals energies of the complex were monitored during the MD simulations and confirmed the energetic stability of the two interactions. ..
  12. Iijima M, Matsuzaki T, Kadoya H, Hatahira S, Hiramatsu S, Jung G, et al. Bionanocapsule-based enzyme-antibody conjugates for enzyme-linked immunosorbent assay. Anal Biochem. 2010;396:257-61 pubmed publisher
    ..Thus, ZZ-BNC is expected to increase the performance of various conventional immunoassays. ..
  13. Huang B, Liu F, Dong X, Sun Y. Molecular mechanism of the affinity interactions between protein A and human immunoglobulin G1 revealed by molecular simulations. J Phys Chem B. 2011;115:4168-76 pubmed publisher
    ..Finally, the binding motif of SpA is constructed, which would help design novel high-affinity ligands of IgG. ..
  14. Hasman H, Moodley A, Guardabassi L, Stegger M, Skov R, Aarestrup F. Spa type distribution in Staphylococcus aureus originating from pigs, cattle and poultry. Vet Microbiol. 2010;141:326-31 pubmed publisher
    ..In conclusion, strains of MSSA CC398 were commonly present in pigs but not present at all in the other reservoirs tested. ..
  15. Holm L, Moody P, Howarth M. Electrophilic affibodies forming covalent bonds to protein targets. J Biol Chem. 2009;284:32906-13 pubmed publisher
    ..Thus electrophilic affibodies combined good specificity with improved detection of protein targets. ..
  16. Lund L, Christensen T, Toone E, Houen G, Staby A, St Hilaire P. Exploring variation in binding of Protein A and Protein G to immunoglobulin type G by isothermal titration calorimetry. J Mol Recognit. 2011;24:945-52 pubmed publisher
    ..In contrast to PrtA, PrtG bound to F(ab')(2) fragment with a Ka value of 5.1 × 10(5) M(-1) ; thus underscoring the usefulness of PrtA as a preferred ligand for generic antibody purification processes. ..
  17. Zhang M, Lute S, Norling L, Hong C, Safta A, O Connor D, et al. A novel, Q-PCR based approach to measuring endogenous retroviral clearance by capture protein A chromatography. Biotechnol Bioeng. 2009;102:1438-47 pubmed publisher
    ..Overall, our results demonstrate that protein A chromatography is a robust retrovirus removal step and CHO retrovirus removal can be directly measured at large scale using Q-PCR assays. ..
  18. Maisuradze G, Liwo A, Ołdziej S, Scheraga H. Evidence, from simulations, of a single state with residual native structure at the thermal denaturation midpoint of a small globular protein. J Am Chem Soc. 2010;132:9444-52 pubmed publisher
    The folding of the B-domain of staphylococcal protein A has been studied by coarse-grained canonical and multiplexed replica-exchange molecular dynamics simulations with the UNRES force field in a broad range of temperatures (270 K < ..
  19. Sisodiya V, Lequieu J, Rodriguez M, McDonald P, Lazzareschi K. Studying host cell protein interactions with monoclonal antibodies using high throughput protein A chromatography. Biotechnol J. 2012;7:1233-41 pubmed publisher
    ..The reduction in the level of host cell proteins differed between antibodies suggesting that the interaction likely varies between individual antibodies but encompasses both an electrostatic and hydrophobic component. ..
  20. Huang B, Liu F, Dong X, Sun Y. Molecular mechanism of the effects of salt and pH on the affinity between protein A and human immunoglobulin G1 revealed by molecular simulations. J Phys Chem B. 2012;116:424-33 pubmed publisher
    ..0. The dissociation mechanism is then used to refine the binding model of SpA to hIgG1. The model is expected to help design high-affinity peptide ligands of IgG. ..
  21. Boi C, Busini V, Salvalaglio M, Cavallotti C, Sarti G. Understanding ligand-protein interactions in affinity membrane chromatography for antibody purification. J Chromatogr A. 2009;1216:8687-96 pubmed publisher
    ..The simulations enabled to elucidate how the interactions of surface, spacer and ligand with IgG, contribute to the formation of the bond between protein and affinity membrane. ..
  22. Kock R, Siam K, Al Malat S, Christmann J, Schaumburg F, Becker K, et al. Characteristics of hospital patients colonized with livestock-associated meticillin-resistant Staphylococcus aureus (MRSA) CC398 versus other MRSA clones. J Hosp Infect. 2011;79:292-6 pubmed publisher
    ..The differences in patient characteristics could explain, at least in part, the relatively low rates of transmission and infection associated with MRSA CC398 in the healthcare setting. ..
  23. Jelsbak L, Ingmer H, Valihrach L, Cohn M, Christiansen M, Kallipolitis B, et al. The chaperone ClpX stimulates expression of Staphylococcus aureus protein A by Rot dependent and independent pathways. PLoS ONE. 2010;5:e12752 pubmed publisher
    ..The current findings emphasize that ClpX has a central role in fine-tuning virulence regulation in S. aureus. ..
  24. Iijima M, Matsuzaki T, Yoshimoto N, Niimi T, Tanizawa K, Kuroda S. Fluorophore-labeled nanocapsules displaying IgG Fc-binding domains for the simultaneous detection of multiple antigens. Biomaterials. 2011;32:9011-20 pubmed publisher
  25. Tackett A, DeGrasse J, Sekedat M, Oeffinger M, Rout M, Chait B. I-DIRT, a general method for distinguishing between specific and nonspecific protein interactions. J Proteome Res. 2005;4:1752-6 pubmed
    ..I-DIRT will be of broad value for studying protein complexes in biological systems that can be metabolically labeled. ..
  26. Huntzinger E, Boisset S, Saveanu C, Benito Y, Geissmann T, Namane A, et al. Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression. EMBO J. 2005;24:824-35 pubmed
    ..Our results further suggest that RNase III is recruited for targeting the paired RNAs. These findings add further complexity to the expression of the S. aureus virulon. ..
  27. Vila J, Ripoll D, Scheraga H. Atomically detailed folding simulation of the B domain of staphylococcal protein A from random structures. Proc Natl Acad Sci U S A. 2003;100:14812-6 pubmed
    The conformational space of the 10-55 fragment of the B-domain of staphylococcal protein A has been investigated by using the electrostatically driven Monte Carlo (EDMC) method...
  28. Sagawa T, Oda M, Morii H, Takizawa H, Kozono H, Azuma T. Conformational changes in the antibody constant domains upon hapten-binding. Mol Immunol. 2005;42:9-18 pubmed
    ..Similar evidence of conformational change upon hapten-binding was also obtained using SpG as a probe. ..
  29. Gomez M, O Seaghdha M, Magargee M, Foster T, Prince A. Staphylococcus aureus protein A activates TNFR1 signaling through conserved IgG binding domains. J Biol Chem. 2006;281:20190-6 pubmed
  30. Mellmann A, Friedrich A, Rosenkötter N, Rothganger J, Karch H, Reintjes R, et al. Automated DNA sequence-based early warning system for the detection of methicillin-resistant Staphylococcus aureus outbreaks. PLoS Med. 2006;3:e33 pubmed
    ..Rapid MRSA outbreak detection, based on epidemiological and spa typing data, is a suitable alternative for classical approaches and can assist in the identification of potential sources of infection. ..
  31. Gustafsson E, Karlsson S, Oscarsson J, Sögård P, Nilsson P, Arvidson S. Mathematical modelling of the regulation of spa (protein A) transcription in Staphylococcus aureus. Int J Med Microbiol. 2009;299:65-74 pubmed publisher
    ..We believe that this mathematical model can be used to evaluate the significance of other putative interactions in the regulatory network governing spa transcription. ..
  32. Faria N, Carriço J, Oliveira D, Ramirez M, De Lencastre H. Analysis of typing methods for epidemiological surveillance of both methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains. J Clin Microbiol. 2008;46:136-44 pubmed
  33. Sato S, Religa T, Daggett V, Fersht A. Testing protein-folding simulations by experiment: B domain of protein A. Proc Natl Acad Sci U S A. 2004;101:6952-6 pubmed
    ..There is a continuing need for combining simulation with experiment to describe folding pathways, and of continued testing to improve predictive methods. ..
  34. Henning P, Magnusson M, Gunneriusson E, Hong S, Boulanger P, Nygren P, et al. Genetic modification of adenovirus 5 tropism by a novel class of ligands based on a three-helix bundle scaffold derived from staphylococcal protein A. Hum Gene Ther. 2002;13:1427-39 pubmed
    ..coding sequence for a disulfide bond-independent three-helix bundle scaffold Z, derived from domain B of Staphylococcal protein A and capable of binding to the Fc portion of immunoglobulin (Ig) G1, could be incorporated into modified ..
  35. Kuhn G, Francioli P, Blanc D. Double-locus sequence typing using clfB and spa, a fast and simple method for epidemiological typing of methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2007;45:54-62 pubmed
    ..The genetic differences found between isolate pairs of long-term carriers and among highly related isolates indicated clonal evolution. A typing scheme based on 500-bp 3' partial sequences of clfB and spa is proposed. ..
  36. Nagaoka M, Akaike T. Single amino acid substitution in the mouse IgG1 Fc region induces drastic enhancement of the affinity to protein A. Protein Eng. 2003;16:243-5 pubmed
    ..This result suggests that a direct and simple modification allows the efficient purification of monoclonal antibody and of fusion protein containing mouse IgG Fc region. ..
  37. Wang H, Liu Y, Yang Y, Deng T, Shen G, Yu R. A protein A-based orientation-controlled immobilization strategy for antibodies using nanometer-sized gold particles and plasma-polymerized film. Anal Biochem. 2004;324:219-26 pubmed
    ..A HP serum concentration as low as 0.41 nM can be determined by this new system. Regenerated simply by rinsing in the acid buffer, the proposed sensor can achieve up to 11 assay cycles without significant loss of sensitivity. ..
  38. Favrin G, Irbäck A, Wallin S. Folding of a small helical protein using hydrogen bonds and hydrophobicity forces. Proteins. 2002;47:99-105 pubmed
    ..amino acid types is developed and tested on a three-helix-bundle protein, a 46-amino acid fragment from staphylococcal protein A. The model does not rely on the widely used Go approximation, which ignores non-native interactions...
  39. Saha K, Bender F, Gizeli E. Comparative study of IgG binding to proteins G and A: nonequilibrium kinetic and binding constant determination with the acoustic waveguide device. Anal Chem. 2003;75:835-42 pubmed
    ..The promise of this detection method is shown by providing quick determination of binding constants with low sample volumes. ..
  40. Ghose S, Hubbard B, Cramer S. Binding capacity differences for antibodies and Fc-fusion proteins on protein A chromatographic materials. Biotechnol Bioeng. 2007;96:768-79 pubmed
  41. Zheng D, Aramini J, Montelione G. Validation of helical tilt angles in the solution NMR structure of the Z domain of Staphylococcal protein A by combined analysis of residual dipolar coupling and NOE data. Protein Sci. 2004;13:549-54 pubmed
    b>Staphylococcal protein A (SpA) is a virulence factor from Staphylococcus aureus that is able to bind to immunoglobulins...
  42. Normark B, Normark S, Norrby Teglund A. Staphylococcal protein A inflames the lungs. Nat Med. 2004;10:780-1 pubmed
  43. Viau M, Longo N, Lipsky P, Zouali M. Staphylococcal protein a deletes B-1a and marginal zone B lymphocytes expressing human immunoglobulins: an immune evasion mechanism. J Immunol. 2005;175:7719-27 pubmed
    ..Since the two B lymphocyte subsets targeted are involved in innate immune functions, our data suggest that crippling of humoral immunity by S. aureus represents an immune evasion mechanism that may aggravate recurrent infections. ..
  44. Itoh K, Sasai M. Flexibly varying folding mechanism of a nearly symmetrical protein: B domain of protein A. Proc Natl Acad Sci U S A. 2006;103:7298-303 pubmed
    ..Such sensitivity in multiple transition state ensembles is a natural consequence of symmetry-breaking in a nearly symmetrical protein. ..
  45. Somerville G, Beres S, Fitzgerald J, Deleo F, Cole R, Hoff J, et al. In vitro serial passage of Staphylococcus aureus: changes in physiology, virulence factor production, and agr nucleotide sequence. J Bacteriol. 2002;184:1430-7 pubmed
    ..aureus undergoes significant phenotypic and genotypic changes during serial passage and suggest that vigilance should be used when extrapolating data obtained from the study of high-passage strains. ..
  46. Silverman G, Goodyear C. Confounding B-cell defences: lessons from a staphylococcal superantigen. Nat Rev Immunol. 2006;6:465-75 pubmed
    ..Agents designed to emulate the properties of B-cell superantigens might also provide new approaches for the treatment of B-cell-mediated autoimmune and neoplastic diseases. ..
  47. Lute S, Norling L, Hanson M, Emery R, Stinson D, Padua K, et al. Robustness of virus removal by protein A chromatography is independent of media lifetime. J Chromatogr A. 2008;1205:17-25 pubmed publisher
    ..Overall, virus clearance by protein A chromatography appears to be extremely robust with respect to media age. ..
  48. Tsutsui Y, Tomizawa K, Nagita M, Michiue H, Nishiki T, Ohmori I, et al. Development of bionanocapsules targeting brain tumors. J Control Release. 2007;122:159-64 pubmed
    ..Moreover, we confirmed the specific delivery of the hybrid BNCs to brain tumors in an in vivo brain tumor model. These results suggest that this new approach using BNCs is a promising system for brain tumor-targeted drug delivery. ..
  49. G mez M, Seaghdha M, Prince A. Staphylococcus aureus protein A activates TACE through EGFR-dependent signaling. EMBO J. 2007;26:701-9 pubmed publisher
    ..Thus, staphylococci exploit the ubiquitous and multifunctional EGFR to regulate the availability of TNFR1 on mucosal and immune cells...
  50. Strommenger B, Kettlitz C, Weniger T, Harmsen D, Friedrich A, Witte W. Assignment of Staphylococcus isolates to groups by spa typing, SmaI macrorestriction analysis, and multilocus sequence typing. J Clin Microbiol. 2006;44:2533-40 pubmed
    ..aureus epidemiology, especially because of ease of use and the advantages of unambiguous sequence analysis as well as reproducibility and exchange of typing data. ..
  51. Jang S, Kim E, Shin S, Pak Y. Ab initio folding of helix bundle proteins using molecular dynamics simulations. J Am Chem Soc. 2003;125:14841-6 pubmed
    ..formation of nativelike structures for the 36-residue villin headpiece and the 46-residue fragment B of Staphylococcal protein A. An implicit solvent model combined with high-temperature MD makes it possible to perform direct folding ..
  52. Foster T. Immune evasion by staphylococci. Nat Rev Microbiol. 2005;3:948-58 pubmed
    ..In contrast, Staphylococcus epidermidis must rely primarily on cell-surface polymers and the ability to form a biolfilm to survive in the host. ..
  53. Hadji Ghasemi F, Gharagozlou S, Ghods R, Roohi A, Khoshnoodi J, Shokri F. Generation and characterization of a mouse monoclonal antibody with specificity similar to staphylococcal protein A (SPA). Hybrid Hybridomics. 2003;22:33-9 pubmed
    ..specificities of human IgG subclasses is binding of Fc fragment of IgG(1), 2, and 4 but, not IgG(3) to staphylococcal protein A (SPA)...