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Chapter 45 : Cellular and Extracellular Defenses against Staphylococcal Infections

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Cellular and Extracellular Defenses against Staphylococcal Infections, Page 1 of 2

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Abstract:

Breaches of the skin and mucosal barriers greatly increase the likelihood of invasive staphylococcal infections, affirming the importance of these peripheral barriers in maintaining a normally asymptomatic host-bacterial relationship. Deficiencies in the mobilization or function of polymorphonuclear leukocytes (PMN) are associated with increased susceptibility to infection by many extracellular bacterial pathogens, including staphylococci. However, more recent studies have revived interest in secretion-based extracellular defenses against staphylococci and other gram-positive bacteria. Secreted antistaphylococcal agents may act alone, providing host defense against bacteria that resist or exceed phagocyte-based defenses, and may also act in concert with resident and mobilized phagocytes to increase antibacterial cytotoxicity of host defenses. In general, the action of PMN at extravascular sites of infection requires a highly regulated series of PMN responses resulting in the directed migration of PMN from blood to sites of infection, sequestration of bacterial prey, and intracellular cytotoxic action. Staphylococcal infections in chronic granulomatous disease (CGD) are overwhelmingly of extravascular nature. This is consistent with the retention of normal clearance function of phagocytes in this disease but also raises the possibility that other mechanisms of host defense against intravascular infections are operative. The acute inflammatory response mobilizes both PMN and extracellular antistaphylococcal activity at the site of bacterial invasion. The chapter focuses on the agents whose mechanism of action against has been most extensively studied. These agents are group IIA phospholipase A2 (PLA2), platelet microbicidal proteins (PMPs) and platelet kinocidins, defensins, and cathelicidins.

Citation: Weiss J, Bayer A, Yeaman M. 2006. Cellular and Extracellular Defenses against Staphylococcal Infections, p 544-559. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch45

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Figures

Image of FIGURE 1
FIGURE 1

Schematic representation of PMN engaged in phagocytosis: attachment and internalization of bacterial prey into the phagocytic vacuole, fusion of cytoplasmic granules with the phagosome to deliver antibacterial peptides and proteins, and mobilization of assembled NADPH oxidase within the phagolysosome. Also indicated are K and H fluxes induced by electrogenic effects of oxidase activation. See text for additional details.

Citation: Weiss J, Bayer A, Yeaman M. 2006. Cellular and Extracellular Defenses against Staphylococcal Infections, p 544-559. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch45
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Image of FIGURE 2
FIGURE 2

Schematic representation of platelets before and after activation. Note changes upon cell activation in cell architecture and surface receptors that facilitate platelet adherence and degranulation. Also note the presence of antimicrobial peptides and proteins (e.g., platelet microbicidal proteins [PMPs], thrombin-induced PMPs [tPMPs], and group IIA PLA2) believed to be stored in the alpha granule. (B) Cross-talk between vascular endothelium, platelets (PLT), and PMN in response to localized infection. Infected endothelium expresses products that either directly (e.g., platelet activating factor [PAF] and interleukin-8 [IL-8]) or indirectly (tissue factor) trigger platelet and PMN recruitment and activation and up-regulate surface receptors for (activated) platelets and PMN. (C) Recruitment, adherence, and activation of platelets and PMN (and endothelium) in juxtaposition to adherent bacteria. Degranulation and activation of respiratory burst in PMN and NO production by endothelium (not shown) lead to localized extracellular mobilization of antimicrobial peptides and proteins and toxic oxygen and nitrogen metabolites. Note that products of platelet degranulation include proteins known (e.g., platelet factor IV) or believed (e.g., tPMPs, PMPs, PLA2) to recruit and/or potentiate antimicrobial functions of PMN. Thus, secreted products may provide mechanisms for extracellular killing of (adherent) bacteria that are refractory to phagocytosis and for enhanced uptake and intracellular destruction of bacteria still susceptible to phagocytosis.

Citation: Weiss J, Bayer A, Yeaman M. 2006. Cellular and Extracellular Defenses against Staphylococcal Infections, p 544-559. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch45
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Image of FIGURE 3
FIGURE 3

Synergy between PMN and extracellular group IIA PLA2 in digestion of phospholipids of during phagocytosis by human PMN. Shown are profiles of metabolically labeled bacterial lipids ( ), resolved by thin-layer chromatography, after incubation for 2 h as indicated. Note that appreciable bacterial phospholipid degradation, at concentration of PLA2 tested, occurs only in combined presence of PLA2 and PMN. Note also substantial conversion of bacterial PG→CL, indicative of a stress response induced shortly after phagocytosis. See text and reference for more details.

Citation: Weiss J, Bayer A, Yeaman M. 2006. Cellular and Extracellular Defenses against Staphylococcal Infections, p 544-559. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch45
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References

/content/book/10.1128/9781555816513.chap45
1. Babior, B. 1999. Review: NADPH oxidase: an update. Blood 93: 1464 1476.
2. Bayer, A. S.,, D. Cheng,, M. R. Yeaman,, G. R. Corey,, R. S. McClelland,, L. J. Harrel,, and V. G. Fowler, Jr. 1998. In vitro resistance to thrombin-induced microbicidal protein among clinical bacteremic isolates of Staphylococcus aureus correlates with an endovascular infectious source. Antimicrob. Agents Chemother. 42: 3169 3172.
3. Bayer, A. S.,, M. D. Ramos,, B. E. Menzies,, M. R. Yeaman,, A. Shen,, and A. L. Cheung. 1997. Hyperproduction of alpha-toxin by Staphylococcus aureus results in paradoxically reduced virulence in experimental endocarditis—host defense role for platelet microbicidal proteins. Infect. Immun. 65: 4652 4660.
4. Beekhuizen, H.,, J. S. van de Gevel,, B. Olsson,, I. J. van Benten,, and R. van Furth. 1997. Infection of human vascular endothelial cells with Staphylococcus aureus induces hyperadhesiveness for human monocytes and granulocytes. J. Immunol. 158: 774 782.
5. Beers, S. A.,, A. G. Buckland,, R. S. Koduri,, W. Cho,, M. H. Gelb,, and D. C. Wilton. 2002. The antibacterial properties of secreted phospholipases A2: a major physiological role for the group IIA enzyme that depends on the very high pI of the enzyme to allow penetration of the bacterial cell wall. J. Biol. Chem. 277: 1788 1793.
6. Belaaouaj, A.,, R. McCarthy,, M. Baumann,, Z. Gao,, T. Ley,, S. Abraham,, and S. Shapiro. 1998. Mice lacking neutrophil elastase reveal impaired host defense against gram-negative bacterial sepsis. Nat. Med. 4: 615 618.
7. Bera, A.,, S. Herbert,, A. Jakob,, W. Vollmer,, and F. Götz. Why are pathogenic staphylococci so lysozyme resistant? The peptidoglycan O-acetyltransferase OatA is the major determinant for lysozyme resistance of Staphylococcus aureus. Mol. Microbiol. 55: 778 787.
8. Brinkmann, V.,, U. Reichard,, C. Goosmann,, B. Fauler,, Y. Uhlemann,, D. S. Weiss,, Y. Weinrauch,, and A. Zychlinsky. 2004. Neutrophil extracellular traps kill bacteria. Science 303: 1532 1535.
9. Buckland, A. G.,, and D. C. Wilton. 2000. The antibacterial properties of secreted phospholipases A(2). Biochim. Biophys. Acta 14880: 71 82.
10. Chapman, A. L.,, M. B. Hampton,, R. Senthilmohan,, C. C. Winterbourn,, and A. J. Kettle. 2002. Chlorination of bacterial and neutrophil proteins during phagocytosis and killing of Staphylococcus aureus. J. Biol. Chem. 277: 9757 9762.
11. Chertov, O.,, D. F. Michiel,, L. Xu,, J. M. Wang,, K. Tani,, W. J. Murphy,, D. L. Longo,, D. D. Taub,, and J. J. Oppenheim. 1996. Identification of defensin-1, defensin-2 and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J. Biol. Chem. 271: 2935 2940.
12. Chevakis, T.,, M. Hussain,, S. M. Kanse,, G. Peters,, R. G. Bretzel,, J. L. Flock,, M. Herrmann,, and K. T. Preissner. 2002. Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes. Nat. Med. 8: 687 693.
13. Clarke, A. J.,, and C. Dupont. 1991. O-acetylated peptidoglycan: its occurrence, pathobiologic significance, and biosynthesis. Can. J. Microbiol. 38: 85 91.
14. Clements, M. O.,, and S. J. Foster. 1999. Stress resistance in Staphylococcus aureus. Trends Microbiol. 7: 458 462.
15. Cole, A. M.,, S. Tahk,, A. Oren,, D. Yoshioka,, Y. H. Kim,, A. Park,, and T. Ganz. 2001. Determinants of Staphylococcus aureus nasal carriage. Clin. Diagn. Lab. Immunol. 8: 1064 1069.
16. Cole, A. M.,, T. Ganz,, A. M. Liese,, M. D. Burdick,, L. Liu,, and R. M. Strieter. 2001. IFN-inducible ELRCXC chemokines display defensin-like antimicrobial activity. J. Immunol. 167: 623 627.
17. Collins, L. V.,, S. A. Kristian,, C. Weidenmaier,, M. Faigle,, K. P. M. van Kessel,, J. A. G. van Strijp,, F. Götz,, B. Neumeister,, and A. Peschel. 2002. Staphylococcus aureus strains lacking D-alanine modifications of teichoic acids are highly susceptible to human neutrophil killing and are virulence attenuated in mice. J. Infect. Dis. 186: 214 219.
18. Cunnion, K. M.,, J. C. Lee,, and M. M. Frank. 2001. Capsule production and growth phase influence binding of complement to Staphylococcus aureus. Infect. Immun. 69: 6796 6803.
19. Cunnion, K. M.,, H. M. Zhang,, and M. M. Frank. 2003. Availability of complement bound to Staphylococcus aureus to interact with membrane complement receptors influences efficiency of phagocytosis. Infect. Immun. 71: 656 662.
20. Dankert, J. 1988. Role of platelets in early pathogenesis of viridans group streptococcal endocarditis: a study of thrombodefensins. Ph.D. thesis. University of Groningen, Groningen, The Netherlands.
21. Dankert, J.,, J. van der Werff,, S. A. J. Zaat,, W. Joldersma,, D. Klein,, and J. Hess. 1995. Involvement of bactericidal factors from thrombin-stimulated platelets in clearance of adherent viridans streptococci in experimental infective endocarditis in rabbits. Infect. Immun. 63: 663 671.
22. de Haas, C. J. C.,, K. E. Veldkamp,, A. Peshel,, F. Weerkamp,, W. J. B. van Wamel,, E. C. J. M. Heezius,, M. J. J. G. Poppelier,, K. P. M. van Kessel,, and J. A. G. van Strijp. 2004. Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial anti-inflammatory agent. J. Exp. Med. 199: 687 695.
23. De Kimpe, S. J.,, M. Kengatharan,, C. Thiemermann,, and J. R. Vane. 1995. The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure. Proc. Natl. Acad. Sci. USA 92: 10359 10363.
24. Dhawan, V. G.,, A. S. Bayer,, and M. R. Yeaman. 1998. Influence of in vitro susceptibility to thrombin-induced platelet microbicidal protein on the progression of experimental Staphylococcus aureus endocarditis. Infect. Immun. 66: 3476 3479.
25. Diamond, G.,, J. P. Russell,, and C. L. Bevins. 1996. Inducible expression of an antibiotic peptide gene in lipopolysaccharide-challenged tracheal epithelial cells. Proc. Natl. Acad. Sci. USA 93: 5156 5160.
26. Dinauer, M. C.,, W. M. Nauseef,, and P. E. Newburger,. 2001. Inherited disorders of phagocyte killing, p. 4857 4887. In C. R. Scriver,, A. L. Beaudet,, W. S. Sly,, D. Valle,, B. Childs,, K. W. Kinzler,, and >B. Vogelstein (ed.), The Metabolic and Molecular Bases of Inherited Diseases. McGraw-Hill, New York, N.Y.
27. Dominiecki, M. E.,, and J. Weiss. 1999. Antibacterial action of extracellular mammalian group IIA phospholipase A2 against grossly clumped Staphylococcus aureus. Infect. Immun. 67: 2299 2305.
28. Donaldson, D. M.,, and J. G. Tew. 1977. Beta-lysin of platelet origin. Bacteriol. Rev. 41: 501 513.
29. Eisenhauer, P. B.,, and R. I. Lehrer. 1992. Mouse neutrophils lack defensins. Infect. Immun. 60: 3446 3447.
30. Elsbach, P.,, J. Weiss,, and O. Levy,. 1999. Oxygen-independent antimicrobial systems of phagocytes, p. 801 817. In J. I. Gallin,, R. Snyderman,, and C. Nathan (ed.), Inflammation. Basic Principles and Clinical Correlates, 3rd ed. Lippincott-Raven, New York, N.Y.
31. Fang, F. 2004. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat. Rev. Microbiol. 2: 820 832.
32. Faurschou, M., and Borregaard, N. 2003. Neutrophil granules and secretory vesicles in inflammation. Microbes Infect. 5: 1317 1328.
33. Femling, J. K.,, W. M. Nauseef,, and J. P. Weiss. 2005. Synergy between extracellular group IIA phospholipase A2 and phagocyte NADPH oxidase in digestion of phospholipids of Staphylococcus aureus ingested by human neutrophils. J. Immunol. 175: 4653 4661.
34. Ferrante, A.,, A. J. Martin,, E. J. Bates,, D. H. B. Goh,, D. P. Harvey,, D. Parsons,, D. A. Rathjen,, G. Russ,, and J.-M. Dayer. 1993. Killing of Staphylococcus aureus by tumor necrosis factor-α-activated neutrophils. J. Immunol. 151: 4821 4828.
35. Foreman-Wykert, A. K. 1999. Determinants of the bactericidal action of mammalian 14 kDa group IIA phospholipase A2 against gram-positive bacteria, p. 113. In Microbiology. New York University, New York, N.Y.
36. Foreman-Wykert, A. K.,, Y. Weinrauch,, P. Elsbach,, and J. Weiss. 1999. Cell-wall determinants of the bactericidal action of group IIA phospholipase A2 against Gram-positive bacteria. J. Clin. Investig. 103: 715 721.
37. Fowler, V. G., Jr.,, G. Sakoulas,, L. M. McIntyre,, V. G. Meka,, R. D. Arbeit,, C. H. Cabell,, M. E. Stryjewski,, G. M. Eliopoulos,, L. B. Reller,, G. R. Corey,, T. Jones,, N. Lucindo,, M. R. Yeaman,, and A. S. Bayer. 2004. Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein. J. Infect. Dis. 190: 1140 1149.
38. Frohm, M.,, H. Gunne,, A. C. Bergman,, B. Agerberth,, T. Bergman,, A. Boman,, S. Liden,, H. Jornvall,, and H. G. Boman. 1996. Biochemical and antibacterial analysis of human wound and blister fluid. Eur. J. Biochem. 237: 86 92.
39. Ganz, T. 1994. Biosynthesis of defensins and other antimicrobial peptides. Ciba Found. Symp. 186: 62 71.
40. Ginsburg, I.,, and M. Lahav. 1983. How are bacterial cells degraded by leukocytes in vivo? An enigma. Clin. Immunol. Newsl. 4: 147 153.
41. Ginsburg, I. 2002. The role of bacteriolysis in the pathophysiology of inflammation, infection and post-infectious sequelae. APMIS 110: 753 770.
42. Goldman, M. J.,, G. M. Anderson,, E. D. Stolzenberg,, U. P. Kari,, M. Zasloff,, and J. M. Wilson. 1997. Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88: 553 560.
43. Gresham, H. D.,, J. H. Lowrance,, T. E. Caver,, B. S. Wilson,, A. L. Cheung,, and F. P. Lindberg. 2000. Survival of Staphylococcus aureus inside neutrophils contributes to infection. J. Immunol. 164: 3713 3722.
44. Hampton, M. B.,, A. J. Kettle,, and C. C. Winterbourn. 1996. Involvement of superoxide and myeloperoxidase in oxygen-dependent killing of Staphylococcus aureus by neutrophils. Infect. Immun. 64: 3512 3517.
45. Hampton, M. B.,, A. J. Kettle,, and C. C. Winterbourn. 1998. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92: 3007 3017.
46. Harwig, S. S.,, T. Ganz,, and R. I. Lehrer. 1994. Neutrophil defensins. Purification, characterization and antimicrobial testing. Methods Enzymol. 236: 160 176.
47. Harwig, S. S.,, L. Tan,, X. D. Qu,, Y. Cho,, P. B. Eisenhauer,, and R. I. Lehrer. 1995. Bactericidal properties of a murine intestinal phospholipase A2. J. Clin. Investig. 95: 603 610.
48. Heumann, D.,, C. Barras,, A. Severin,, M. P. Glauser,, and A. Tomasz. 1994. Gram-positive cell walls stimulate synthesis of tumor necrosis factor alpha and interleukin-6 by human monocytes. Infect. Immun. 62: 2715 2721.
49. Hristova, K.,, M. E. Selsted,, and S. H. White. 1996. Interactions of monomeric rabbit neutrophil defensin with bilayers: comparison with dimeric human defensin HNP-2. Biochemistry 35: 11888 11894.
50. Hubbard, R. C.,, F. Ogushi,, G. A. Fells,, A. M. Cantin,, S. Jallat,, M. Courtney,, and R. G. Crystal. 1987. Oxidants spontaneously released by alveolar macrophages of cigarette smokers can inactivate the active site of alpha 1-antitrypsin, rendering it ineffective as an inhibitor of neutrophil elastase. J. Clin. Investig. 80: 1289 1295.
51. Hultgren, O.,, H.-P. Eugster,, J. D. Sedgwick,, H. Körner,, and A. Tarkowski. 1998. TNF/lymphotoxin-α double mutant mice resist septic arthritis but display increased mortality in response to Staphylococcus aureus. J. Immunol. 161: 5937 5942.
52. Ing, M. B.,, L. Baddour,, and A. S. Bayer,. 1997. Staphylococcal bacteremia and infective endocarditis—pathogenesis, diagnosis and complications. In G. Archer, and K. Crossley (ed.), Staphylococci and Staphylococcal Diseases. Churchill-Livingstone Publishers, New York, N.Y.
53. Jackson, S. H.,, J. I. Gallin,, and S. M. Holland. 1995. The p47phox mouse knock-out model of chronic granulomatous disease. J. Exp. Med. 182: 751 758.
54. Kallajoki, M.,, and T. J. Nevalainen,. 1997. Expression of Group II phospholipase A2 in human tissues, p. 8 16. In W. Uhl,, T. J. Nevalainen,, and M. W. Buchler (ed.), Phospholipase A2: Basic and Clinical Aspects in Inflammatory Diseases, vol. 24. S. Karger, Basel, Switzerland.
55. Kapral, F. A. 1966. Clumping of Staphylococcus aureus in the peritoneal cavity of mice. J. Bacteriol. 92: 1188 1195.
56. Karakawa, W. W.,, A. Sutton,, R. Schneerson,, A. Karpas,, and W. F. Vann. 1988. Capsular antibodies induce typespecific phagocytosis of capsulated Staphylococcus aureus by human polymorphonuclear leukocytes. Infect. Immun. 56: 1090 1095.
57. Katz, S. S.,, Y. Weinrauch,, R. S. Munford,, P. Elsbach,, and J. Weiss. 1999. Lipopolysaccharide deacylation following extracellular or intracellular killing of Escherichia coli by rabbit inflammatory peritoneal exudates. J. Biol. Chem. 274: 36579 36584.
58. Koo, S.-P.,, A. S. Bayer,, R. A. Proctor,, H.-G. Sahl,, and M. R. Yeaman. 1996. Staphylocidal action of platelet microbicidal protein is not solely dependent on intact transmembrane potential. Infect. Immun. 60: 1070 1074.
59. Koo, S.-P.,, M. R. Yeaman,, and A. S. Bayer. 1996. Staphylocidal action of platelet microbicidal protein is modified by microenvironment and target cell growth phase. Infect. Immun. 64: 3758 3764.
60. Koo, S.-P.,, M. R. Yeaman,, C. C. Nast,, and A. S. Bayer. 1997. The bacterial cell membrane is a principal target for the staphylocidal action of thrombin-induced platelet microbicidal protein. Infect. Immun. 65: 4795 4800.
61. Koprivnjak, T.,, A. Peschel,, M. H. Gelb,, N. S. Liang,, and J. P. Weiss. 2002. Role of charge properties of bacterial envelope in bactericidal action of human group IIA phospholipase A2 against Staphylococcus aureus. J. Biol. Chem. 277: 47636 47644.
62. Kristian, S. A.,, M. Dürr,, J. A. G. Van Strijp,, B. Neumeister,, and A. Peschel. 2003. MprF-mediated lysinylation of phospholipids in Staphylococcus aureus leads to protection against oxygen-independent neutrophil killing. Infect. Immun. 71: 546 549.
63.. Kudo, I.,, and M. Murakami. 2002. Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat. 68-69: 3 58.
64. Kusonoki, T.,, E. Hailman,, T. S. C. Juan,, H. S. Lichenstein,, and S. D. Wright. 1995. Molecules from Staphylococcus aureus that bind CD14 and stimulate innate immune responses. J. Exp. Med. 182: 1673 1682.
65. Laine, V. J.,, D. S. Grass,, and T. J. Nevalainen. 1999. Protection by group II phospholipase A2 against Staphylococcus aureus. J. Immunol. 162: 7402 7408.
66. Lee, J. C. 1996. The prospects for developing a vaccine against Staphylococcus aureus. Trends Microbiol. 4: 162 166.
67. Lee, J. C.,, J.-S. Park,, S. E. Shepherd,, V. Carey,, and A. Fattom. 1997. Protective efficacy of antibodies to the Staphylococcus aureus type 5 capsular polysaccharide in a modified model of endocarditis in rats. Infect. Immun. 65: 4146 4151.
68. Lehrer, R. I. 2004. Primate defensins. Nat. Rev. Microbiol. 2: 727 738.
69. Levy, O.,, C. E. Ooi,, J. Weiss,, R. I. Lehrer,, and P. Elsbach. 1994. Individual and synergistic effects of rabbit granulocyte proteins on Escherichia coli. J. Clin. Investig. 94: 672 682.
70. Lowy, F. D. 1998. Medical progress: Staphylococcus aureus infections. N. Engl. J. Med. 339: 520 532.
71. Madsen, L. M.,, M. Inada,, and J. Weiss. 1996. Determinants of activation by complement of group II phospholipase A2 acting against Escherichia coli. Infect. Immun. 64: 2425 2430.
72. Mandell, G. L. 1975. Catalase, superoxide dismutase, and virulence of Staphylococcus aureus. In vitro and in vivo studies with emphasis on staphylococcal—leukocyte interaction. J. Clin. Investig. 55: 561 566.
73. McInnes, I. B.,, B. Leung,, X. Q. Wei,, C. C. Gemmell,, and F. Y. Liew. 1998. Septic arthritis following Staphylococcus aureus infection in mice lacking inducible nitric oxide synthase. J. Immunol. 160: 308 315.
74. Melly, M. A.,, J. B. Thomison,, and D. E. Rogers. 1960. Fate of staphylococci within human leukocytes. J. Exp. Med. 112: 1121 1130.
75. Menzies, B. E.,, and I. Kourteva. 1998. Internalization of Staphylococcus aureus by endothelial cells induces apoptosis. Infect. Immun. 66: 5994 5998.
76. Messina, C. G. M.,, E. P. Reeves,, J. Roes,, and A. W. Segal. 2002. Catalase negative Staphylococcus aureus retain virulence in mouse model of chronic granulomatous disease. FEBS Lett. 518: 107 110.
77. Midorikawa, K.,, K. Ouhara,, H. Komatsuzawa,, T. Kawai,, S. Yamada,, T. Fujiwara,, K. Yamazaki,, K. Sayama,, M. A. Taubman,, H. Kurihara,, K. Hashimoto,, and M. Sugai. 2003. Staphylococcus aureus susceptibility to innate antimicrobial peptides, β-defensins and CAP18, expressed by human keratinocytes. Infect. Immun. 71: 3730 3739.
78. Morath, S.,, A. Geyer,, and T. Hartung. 2001. Structure-activity relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus. J. Exp. Med. 193: 393 397.
79. Murakami, M.,, Y. Nakatani,, and I. Kudo. 1996. Type II secretory phospholipase A2 associated with cell surfaces via C-terminal heparin-binding lysine residues augments stimulus-initiated delayed prostaglandin generation. J. Biol. Chem. 271: 30041 30051.
80. Murdoch, C.,, and A. Finn. 2000. Chemokine receptors and their role in inflammation and infectious diseases. Blood 95: 3032 3043.
81. Nathan, C.,, and M. U. Shiloh. 2000. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc. Natl. Acad. Sci. USA 97: 8841 8848.
82. Nauseef, W. M. 2004. Assembly of the phagocyte NADPH oxidase. Histochem. Cell Biol. 122: 277 291.
83. Neth, O.,, D. L. Jack,, M. Johnson,, N. J. Klein,, and M. W. Turner. 2002. Enhancement of complement activation and opsonophagocytosis by complexes of mannose-binding lectin with mannose-binding lectin-associated serine protease after binding to Staphylococcus aureus. J. Immunol. 169: 4430 4436.
84. Nilsdotter-Augustinsson, A.,, A. Wilsson,, J. Larsson,, O. Stendahl,, L. Öhman,, and H. Lundqvist-Gustafsson. 2004. Staphylococcus aureus, but not Staphylococcus epidermidis, modulates the oxidative response and induces apoptosis in human neutrophils. APMIS 112: 109 118.
85. Ong, P. Y.,, T. Ohtake,, C. Brandt,, I. Strickland,, M. Boguniewicz,, T. Ganz,, R. L. Gallo,, and D. Y. M. Leung. 2002. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N. Engl. J. Med. 347: 1151 1160.
86. O’Riordan, K.,, and J. C. Lee. 2004. Staphylococcus aureus capsular polysaccharides. Clin. Microbiol. Rev. 17: 218 234.
87. Patti, J. M. 2004. A humanized monoclonal antibody targeting Staphylococcus aureus. Vaccine 22S: S39 S43.
88. Peschel, A. 2002. How do bacteria resist human antimicrobial peptides? Trends Microbiol. 10: 179 186.
89. Peterson, P. K.,, B. J. Wilkinson,, Y. Kim,, D. Schmeling,, S. D. Douglas,, P. G. Quie,, and J. Verhoef. 1978. The key role of peptidoglycan in the opsonization of Staphylococcus aureus. J. Clin. Investig. 61: 597 609.
90. Pollock, J. D.,, D. A. Williams,, M. A. Gifford,, L. L. Li,, X. Du,, J. Fisherman,, S. H. Orkin,, C. M. Doerschuk,, and M. C. Dinauer. 1995. Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production. Nat. Genet. 9: 202 209.
91. Proctor, R. A.,, J. M. Balwit,, and O. Vesga. 1994. Variant subpopulations of Staphylococcus aureus as a cause of persistent infections. Infect. Agents Dis. 3: 302 312.
92. Qu, X. D.,, and R. I. Lehrer. 1998. Secretory phospholipase A2 is the principal bactericide for staphylococci and other gram-positive bacteria in human tears. Infect. Immun. 66: 2791 2797.
93. Quie, P. G.,, J. G. White,, B. Holmes,, and R. A. Good. 1967. In vitro bactericidal capacity of human polymorphonuclear leukocytes: diminished activity in chronic granulomatous disease of childhood. J. Clin. Investig. 46: 668 679.
94. Reeves, E. P.,, H. Lu,, H. L. Jacobs,, C. G. Messina,, S. Bolsover,, G. Gabella,, E. O. Potma,, A. Warley,, J. Roes,, and A. W. Segal. 2002. Killing activity of neutrophils is mediated through activation of proteases by K + flux. Nature 416: 291 297.
95. Reeves, E. P.,, M. Nagl,, J. Godovac-Zimmermann,, and A. W. Segal. 2003. Reassessment of the microbicidal activity of reactive oxygen species and hypochlorous acid with reference to the phagocytic vacuole of the neutrophil granulocyte. J. Med. Microbiol. 52: 643 651.
96. Rennermalm, A.,, M. Nilsson,, and J. I. Flock. 2004. The fibrinogen binding protein of Staphylococcus epidermidis is target for opsonic antibodies. Infect. Immun. 72: 3081 3083.
97. Schonwetter, B. S.,, E. D. Stolzenberg,, and M. A. Zasloff. 1995. Epithelial antibiotics induced at sites of inflammation. Science 267: 1645 1648.
98. Segal, A. W.,, A. M. Harper,, R. C. Garcia,, and D. Merzbach. 1982. The action of cells from patients with chronic granulomatous disease on Staphylococcus aureus. J. Med. Microbiol. 15: 441 449.
99. Shafer, W. M.,, and V. C. Onunka. 1989. Mechanism of staphylococcal resistance to non-oxidative antimicrobial action of neutrophils: importance of pH and ionic strength in determining the bactericidal action of cathepsin G. J. Gen. Microbiol. 135: 825 830.
100. Shi, L.,, K. Takahashi,, J. Dundee,, S. Shahroor-Karni,, S. Thie,, C. Jensenius,, F. Gad,, M. R. Hamblin,, K. N. Sastry,, and R. A. B. Ezekowitz. 2004. Mannose-binding lectin-deficient mice are susceptible to infection with Staphylococcus aureus. J. Exp. Med. 199: 1379 1390.
101. Shimoda, M.,, K. Ohki,, Y. Shimamota,, and O. Kohashi. 1995. Morphology of defensin-treated Staphylococcus aureus. Infect. Immun. 63: 2886 2891.
102. Singh, P. K.,, B. F. Tack,, P. B. McCray, Jr.,, and M. J. Welsh. 2000. S ynergistic and additive killing by antimicrobial factors found in human airway surface liquid. Am. J. Physiol. Lung Cell Mol. Physiol. 279: L799 L805.
103. Six, D. A.,, and E. A. Dennis. 2000. The expanding superfamily of phospholipase A(2) enzymes: classification and characterization. Biochim. Biophys. Acta 1488: 1 19.
104. Sorensen, O. E.,, P. Follin,, A. H. Jonhsen,, J. Calafat,, G. S. Tjabringa,, P. S. Hiemstra,, and N. Borregaard. 2001. Human cathelicidin, hCAP18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 97: 3951 3959.
105. Staudinger, B. J.,, M. A. Oberdoerster,, P. J. Lewis,, and H. Rosen. 2002. mRNA expression profiles for Escherichia coli ingested by normal and phagocyte-oxidase-deficient human neutrophils. J. Clin. Investig. 110: 1151 1163.
106. Sullam, P. M.,, U. Frank,, M. G. Tauber,, M. Yeaman,, A. Bayer,, and H. F. Chambers. 1993. Effect of thrombocytopenia on the early course of streptococcal endocarditis. J. Infect. Dis. 168: 910 914.
107. Tang, Y. Q.,, M. R. Yeaman,, and M. E. Selsted. 2002. Antimicrobial peptides from human platelets. Infect. Immun. 70: 6524 6533.
108. Territo, M. C.,, T. Ganz,, M. E. Selsted,, and R. Lehrer. 1989. Monocyte-chemotactic activity of defensins from human neutrophils. J. Clin. Investig. 84: 2017 2020.
109. Thakker, M.,, J.-S. Park,, V. Carey,, and J. C. Lee. 1998. Staphylococcus aureus serotype 5 capsular polysaccharide is antiphagocytic and enhances bacterial virulence in a murine bacteremia model. Infect. Immun. 66: 5183 5189.
110. Trier, D.,, K. D. Gank,, A. S. Bayer,, and M. R. Yeaman. 2000. Staphylococcus aureus elicits platelet antimicrobial responses via an ADP-dependent pathway. Program Abstr. 40th Intersci. Conf. Antimicrob. Agents Chemother. abstr. 1010. American Society for Microbiology, Washington, D.C.
111. Valore, E. V.,, E. Martin,, S. S. Harwig,, and T. Ganz. 1996. Intramolecular inhibition of human defensin HNP-1 by its propiece. J. Clin. Investig. 97: 1624 1629.
112. Vaudaux, P. E.,, G. Zulian,, E. Huggler,, and F. A. Waldvogel. 1985. Attachment of Staphylococcus aureus to polymethymethacrylate increases its resistance to phagocytosis in foreign body infection. Infect. Immun. 50: 472 477.
113. Verbrugh, H. A.,, P. K. Peterson,, B. Y. Nguyen,, S. P. Sisson,, and Y. Kim. 1982. Opsonization of encapsulated Staphylococcus aureus: the role of specific antibody and complement. J. Immunol. 129: 1681 1687.
114. Verdrengh, M.,, T. A. Springer,, J.-C. Gutierrez,, and A. Tarkowski. 1996. A role of intercellular adhesion molecule 1 in pathogenesis of staphylococcal arthritis and in host defense against staphylococcal bacteremia. Infect. Immun. 64: 2804 2807.
115. Voyich, J. M.,, K. R. Braughton,, D. E. Sturdevant,, C. Vuong,, S. D. Kobayashi,, S. F. Porcella,, M. Otto,, J. M. Musser,, and F. R. DeLeo. 2004. Engagement of the pathogen survival response used by group A Streptococcus to avert destruction by innate host defense. J. Immunol. 173: 1194 1201.
116. Waldvogel, F. A. 1999. New resistance in Staphylococcus aureus. N. Engl. J. Med. 340: 556 557.
117. Walton, E. 1978. The preparation, properties and action on Staphylococcus aureus of purified fractions from the cationic proteins of rabbit polymorphonuclear leukocytes. Br. J. Exp. Pathol. 59: 416 431.
118. Weinrauch, Y.,, C. Abad,, N. S. Liang,, S. F. Lowry,, and J. Weiss. 1998. Mobilization of potent plasma bactericidal activity during systemic bacterial challenge: role of group IIA phospholipase A2. J. Clin. Investig. 102: 633 638.
119. Weinrauch, Y.,, P. Elsbach,, L. M. Madsen,, A. Foreman,, and J. Weiss. 1996. The potent anti- Staphylococcus aureus activity of a sterile rabbit inflammatory fluid is due to a 14-kD phospholipase A2. J. Clin. Investig. 97: 250 257.
120. Weinrauch, Y.,, S. S. Katz,, R. S. Munford,, P. Elsbach,, and J. Weiss. 1999. Deacylation of purified lipopolysaccharide by cellular and extracellular components of a sterile rabbit peritoneal inflammatory exudate. Infect. Immun. 67: 3376 3382.
121. Weiss, J.,, L. Kao,, M. Victor,, and P. Elsbach. 1987. Respiratory burst facilitates the digestion of Escherichia coli killed by polymorphonuclear leukocytes. Infect. Immun. 55: 2142 2147.
122. Weiss, J.,, M. Inada,, P. Elsbach,, and R. M. Crowl. 1994. Structural determinants of the action against Escherichia coli of a human inflammatory fluid phospholipase A2 in concert with polymorphonuclear leukocytes. J. Biol. Chem. 269: 26331 26337.
123. Weiss, J.,, M. Victor,, O. Stendahl,, and P. Elsbach. 1982. Killing of Gram-negative bacteria by polymorphonuclear leukocytes: the role of an O2-independent bactericidal system. J. Clin. Investig. 69: 959 970.
124. Welling, M. M.,, P. S. Hiemstra,, M. T. van den Barselaar,, A. Paulusma-Annema,, P. H. Nibbering,, E. K. J. Pauwels,, and W. Calame. 1998. Antibacterial activity of human neutrophil defensins in experimental infections in mice is accompanied by increased leukocyte accumulation. J. Clin. Investig. 102: 1583 1590.
125. White, S. H.,, W. C. Wimley,, and M. E. Selsted. 1995. Structure, function, and membrane integration of defensins. Curr. Opin. Struct. Biol. 5: 521 527.
126. Woodman, R.,, R. Erickson,, J. Rae,, H. Jaffe,, and J. Curnutte. 1992. Prolonged recombinant interferon-γ therapy in chronic granulomatous disease: evidence against enhanced neutrophil oxidase activity. Blood 79: 1558 1562.
127. Wright, G.,, C. E. Ooi,, J. Weiss,, and P. Elsbach. 1990. Purification of a cellular (granulocyte) and an extracellular (serum) phospholipase A2 that participate in the destruction of Escherichia coli in a rabbit inflammatory exudate. J. Biol. Chem. 265: 6675 6681.
128. Wright, G. C.,, J. Weiss,, K.-S. Kim,, H. Verheij,, and P. Elsbach. 1990. Bacterial phospholipid hydrolysis enhances the destruction of Escherichia coli ingested by rabbit neutrophils. Role of cellular and extracellular phospholipases. J. Clin. Investig. 85: 1925 1935.
129. Wu, T.,, M. R. Yeaman,, and A. S. Bayer. 1994. Resistance to platelet microbicidal protein in vitro among bacteremic staphylococcal and viridans streptococcal isolates correlates with an endocarditis source. Antimicrob. Agents Chemother. 38: 729 732.
130. Xiong, Y. Q.,, M. R. Yeaman,, and A. S. Bayer. 1999. In vitro antibacterial activities of platelet microbicidal protein and neutrophil defensin against Staphylococcus aureus are influenced by antibiotics differing in mechanism of action. Antimicrob Agents Chemother. 43: 1111 1117.
131. Yang, D.,, Q. Chen,, D. M. Hoover,, P. Staley,, K. D. Tucker,, J. Lubkowski,, and J. J. Oppenheim. 2003. Many chemokines including CCL20 / MIP-3 alpha display antimicrobial activity. J. Leukoc. Biol. 74: 448 455.
132. Yao, L.,, V. Bengualid,, F. D. Lowy,, J. J. Gibbons,, V. B. Hatcher,, and J. W. Berman. 1995. Internalization of Staphylococcus aureus by endothelial cells induces cytokine gene expression. Infect. Immun. 63: 1835 1839.
133. Yeaman, M. R. 1997. The role of platelets in antimicrobial host defense. Clin. Infect. Dis. 25: 951 970.
134. Yeaman, M. R.,, A. S. Bayer,, S.-P. Koo,, W. Foss,, and P. M. Sullam. 1998. Platelet microbicidal proteins and neutrophil defensin disrupt the Staphylococcus aureus cytoplasmic membrane by distinct mechanisms of action. J. Clin. Investig. 101: 178 187.
135. Yeaman, M. R.,, A. S. Ibrahim,, J. E. Edwards,, A. S. Bayer,, and M. A. Ghannoum. 1993. Thrombin-induced platelet microbicidal protein is fungicidal in vitro. Antimicrob. Agents Chemother. 37: 546 553.
136. Yeaman, M. R.,, D. C. Norman,, and A. S. Bayer. 1992. Platelet microbicidal protein enhances the bactericidal and post-antibiotic effects in Staphylococcus aureus. Antimicrob. Agents Chemother. 36: 1665 1660.
137. Yeaman, M. R.,, A. Shen,, Y. Tang,, A. S. Bayer,, and M. A. Selsted. 1997. Isolation and antimicrobial activity of microbicidal proteins from rabbit platelets. Infect. Immun. 65: 1023 1031.
138. Yeaman, M. R.,, P. R. Sullam,, P. F. Dazin,, and A. S. Bayer. 1994. Platelet microbicidal protein alone and in combination with antibiotics reduces adherence of Staphylococcus aureus to platelets in vitro. Infect. Immun. 62: 3416 3423.
139. Yount, N. Y.,, K. D. Gank,, Y. Q. Xiong,, A. S. Bayer,, T. Pender,, W. H. Welch,, and M. R. Yeaman. 2004. Platelet microbicidal protein 1: structural themes of a multifunctional antimicrobial peptide. Antimicrob. Agents Chemother. 48: 4395 4404.
140. Yount, N. Y.,, and M. R. Yeaman. 2004. Multidimensional signatures in antimicrobial peptides. Proc. Natl. Acad. Sci. USA 101: 7363 7368.
141. Zanetti, M. 2004. Cathelicidin, multifunctional proteins of the innate immunity. J. Leukoc. Biol. 75: 39 48.
142. Zarember, K. A.,, S. S. Katz,, B. F. Tack,, L. Doukhan,, J. Weiss,, and P. Elsbach. 2002. Host defense functions of proteolytically processed and parent (unprocessed) cathelicidins of rabbit granulocytes. Infect. Immun. 70: 569 576.
143. Zhao, C.,, I. Wang,, and R. I. Lehrer. 1996. Widespread expression of beta-defensin hB D-1 in human secretory glands and epithelial cells. FEBS Lett. 396: 319 322.
144. Zimmermann, G. R.,, P. Legault,, M. E. Selsted,, and A. Pardi. 1995. Solution structure of bovine neutrophil beta-defensin-12: the peptide fold of the beta-defensin is identical to that of the classical defensins. Biochemistry 34: 13663 13671.

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