1887

Microbiology Society logo

Volume 153, Issue 4

susceptibility of to thrombin-induced platelet microbicidal protein-1 (tPMP-1) is influenced by cell membrane phospholipid composition and asymmetry Free

Abstract

Thrombin-induced platelet microbicidal proteins (e.g. tPMP-1) are small cationic peptides released from mammalian platelets. As the cytoplasmic membrane (CM) is a primary target of tPMPs, distinct CM characteristics are likely to affect the cells' susceptibility profiles. In , CM surface charge and hydrophobicity are principally determined by the content and distribution of its three major phospholipid (PL) constituents: negatively charged phosphatidylglycerol (PG) and cardiolipin (CL) and positively charged lysyl-PG (LPG). PL composition profiles, and inner vs outer CM leaflet PL distributions, were compared in an isogenic tPMP-susceptible (tPMP) and -resistant (tPMP) strain pair (ISP479C vs ISP479R respectively). All PLs were asymmetrically distributed between the outer and inner CM leaflets in both strains. However, in ISP479R, the outer CM leaflet content of LPG was significantly increased vs ISP479C (27.3±11.0 % vs 18.6±7.0 % respectively; =0.05). This observation correlated with reduced binding of the cationic proteins cytochrome , poly--lysine, tPMP-1 and the tPMP-1-mimetic peptide, RP1, to tPMP-1 whole cells and to model liposomal CMs with LPG content and distribution similar to that of tPMP-1 strains. Collectively, selected CM parameters correlated with reduced staphylocidal capacities of tPMP-1 against certain strains, including relative increases in outer CM leaflet positive charge and reduced surface binding of cationic molecules. These findings offer new insights into mechanisms of antimicrobial peptide susceptibility and resistance in .

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): BHI, brain heart infusion , C6-NBD-PG, 1-palmitoyl-2-[(6-NBD-amino)hexanoyl-sn-glycero-3-[phospho-rac-(1-glycerol)]ammonium salt , CAP, cationic antimicrobial peptide , CL, cardiolipin , CM, cytoplasmic membrane , DP-LPG, 1,2-dipalmitoyl-sn-glycerol-3-(phospho-3-lysylglycerol) , DPPG, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol , LPG, lysyl-phosphatidylglycerol , NAO, 10-N-nonyl acridine orange , NBD, 7-nitro-2,1,3-benzoxadiazol-4-yl , PG, phosphatidylglycerol , PL, phospholipid , PMP, platelet microbicidal protein , tPMP-1, thrombin-induced PMP-1 , tPMPR, tPMP-resistant and tPMPS, tPMP-susceptible
SGM
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2006/003111-0
2007-04-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/micro/153/4/1187.html?itemId=/content/journal/micro/10.1099/mic.0.2006/003111-0&mimeType=html&fmt=ahah

References

  1. Angeletti C., Nichols J. W. 1998; Dithionite quenching rate measurement of the inside-outside membrane bilayer distribution of 7-nitrobenz-2-oxa-1,3-diazol-4-yl-labeled phospholipids. Biochemistry 37:15114–15119 [CrossRef]
     [Google Scholar]
  2. Balasubramanian K., Gupta C. M. 1996; Transbilayer phosphatidylethanolamine movements in yeast plasma membranes. Evidence for protein-mediated, energy-dependent mechanism. Eur J Biochem 240:798–806 [CrossRef]
     [Google Scholar]
  3. Balch C., Morris R., Brooks E., Sleight R. G. 1994; The use of N -(7-nitrobenz-2-oxa-1,3-diazole-4-yl)-labeled lipids in determining transmembrane lipid distribution. Chem Phys Lipids 70:205–212 [CrossRef]
     [Google Scholar]
  4. Bates D. M., von Eiff C., McNamara P. J., Peters G., Yeaman M. R., Bayer A. S., Proctor R. A. 2003; Staphylococcus aureus menD and hemB mutants are as infective as the parent strains, but the menadione biosynthetic mutant persists within the kidney. J Infect Dis 187:1654–1661 [CrossRef]
     [Google Scholar]
  5. Bayer A. S., Cheng D., Yeaman M. R., Corey G. R., McClelland R. S., Harrel L. J., Fowler V. G. Jr 1998; In vitro resistance to thrombin-induced platelet microbicidal protein among clinical bacteremic isolates of Staphylococcus aureus correlates with an endovascular infectious source. Antimicrob Agents Chemother 42:3169–3172
     [Google Scholar]
  6. Bayer A. S., Prasad R., Chandra J., Koul A., Smriti M., Varma A., Skurray R. A., Firth N., Brown M. H. & other authors 2000; In vitro resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein is associated with alterations in cytoplasmic membrane fluidity. Infect Immun 68:3548–3553 [CrossRef]
     [Google Scholar]
  7. Bayer A. S., McNamara P., Yeaman M. R., Lucindo N., Jones T., Cheung A. L., Sahl H. G., Proctor R. A. 2006; Transposon disruption of the complex I NADH oxidoreductase gene ( snoD ) in Staphylococcus aureus is associated with reduced susceptibility to the microbicidal activity of thrombin-induced platelet microbicidal protein 1. J Bacteriol 188:211–222 [CrossRef]
     [Google Scholar]
  8. Brogden K. A. 2005; Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?. Nat Rev Microbiol 3:238–250 [CrossRef]
     [Google Scholar]
  9. Cerbon J., Calderon V. 1995; Generation, modulation and maintenance of the plasma membrane asymmetric phospholipid composition in yeast cells during growth: their relation to surface potential and membrane protein activity. Biochim Biophys Acta 1235:100–106 [CrossRef]
     [Google Scholar]
  10. Dekkers D. W., Comfurius P., van Gool R. G., Bevers E. M., Zwaal R. F. 2000; Multidrug resistance protein 1 regulates lipid asymmetry in erythrocyte membranes. Biochem J 350:531–535 [CrossRef]
     [Google Scholar]
  11. Dhawan V. K., Yeaman M. R., Cheung A. L., Kim E., Sullam P. M., Bayer A. S. 1997; Phenotypic resistance to thrombin-induced platelet microbicidal protein in vitro is correlated with enhanced virulence in experimental endocarditis due to Staphylococcus aureus . Infect Immun 65:3293–3299
     [Google Scholar]
  12. Diaz C., Schroit A. J. 1996; Role of translocases in the generation of phosphatidylserine asymmetry. J Membr Biol 151:1–9 [CrossRef]
     [Google Scholar]
  13. Dixit B. L., Gupta C. M. 1998; Role of the actin cytoskeleton in regulating the outer phosphatidylethanolamine levels in yeast plasma membrane. Eur J Biochem 254:202–206 [CrossRef]
     [Google Scholar]
  14. Doerrler W. T., Gibbons H. S., Raetz C. R. 2004; MsbA-dependent translocation of lipids across the inner membrane of Escherichia coli . J Biol Chem 279:45102–45109 [CrossRef]
     [Google Scholar]
  15. Dogra S., Krishnamurthy S., Gupta V., Dixit B. L., Gupta C. M., Sanglard D., Prasad R. 1999; Asymmetric distribution of phosphatidylethanolamine in C. albicans : possible mediation by CDR1, a multidrug transporter belonging to ATP binding cassette (ABC) superfamily. Yeast 15:111–121 [CrossRef]
     [Google Scholar]
  16. Fadok V. A., Bratton D. L., Rose D. M., Pearson A., Ezekewitz R. A., Henson P. M. 2000; A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85–90 [CrossRef]
     [Google Scholar]
  17. Fowler V. G. Jr, McIntyre L. M., Yeaman M. R., Peterson G. E., Barth Reller L., Corey G. R., Wray D., Bayer A. S. 2000; In vitro resistance to thrombin-induced platelet microbicidal protein in isolates of Staphylococcus aureus from endocarditis patients correlates with an intravascular device source. J Infect Dis 182:1251–1254 [CrossRef]
     [Google Scholar]
  18. Gallet P. F., Maftah A., Petit J. M., Denis-Gay M., Julien R. 1995; Direct cardiolipin assay in yeast using the red fluorescence emission of 10- N -nonyl acridine orange. Eur J Biochem 228:113–119 [CrossRef]
     [Google Scholar]
  19. Gallet P. F., Petit J. M., Maftah A., Zachowski A., Julien R. 1997; Asymmetrical distribution of cardiolipin in yeast inner mitochondrial membrane triggered by carbon catabolite repression. Biochem J 324:627–634
     [Google Scholar]
  20. Grant A. M., Hanson P. K., Malone L., Nichols J. W. 2001; NBD-labeled phosphatidylcholine and phosphatidylethanolamine are internalized by transbilayer transport across the yeast plasma membrane. Traffic 2:37–50 [CrossRef]
     [Google Scholar]
  21. Haines T. H. 2001; Do sterols reduce proton and sodium leaks through lipid bilayers?. Prog Lipid Res 40:299–324 [CrossRef]
     [Google Scholar]
  22. Hakomori S. 2003; Structure, organization, and function of glycosphingolipids in membrane. Curr Opin Hematol 10:16–24 [CrossRef]
     [Google Scholar]
  23. Horsburgh M. J., Aish J. L., White I. J., Shaw L., Lithgow J. K., Foster S. J. 2002; Sigma B modulates virulence determinant expression and stress resistance: characterization of a functional rsbU strain derived from Staphylococcus aureus 8325-4. J Bacteriol 184:5457–5467 [CrossRef]
     [Google Scholar]
  24. Hrafnsdottir S., Nichols J. W., Menon A. K. 1997; Transbilayer movement of fluorescent phospholipids in Bacillus megaterium membrane vesicles. Biochemistry 36:4969–4978 [CrossRef]
     [Google Scholar]
  25. Huijbregts R. P., de Kroon A. I., de Kruijff B. 1998; Rapid transmembrane movement of newly synthesized phosphatidyl-ethanolamine across the inner membrane of Escherichia coli . J Biol Chem 273:18936–18942 [CrossRef]
     [Google Scholar]
  26. Kates M., Syz J. Y., Gosser D., Haines T. H. 1993; pH-dissociation characteristics of cardiolipin and its 2′-deoxy analogue. Lipids 28:877–882 [CrossRef]
     [Google Scholar]
  27. Kol M. A., de Kruijff B., de Kroon A. I. 2002; Phospholipid flip-flop in biogenic membranes: what is needed to connect opposite sides. Semin Cell Dev Biol 13:163–170 [CrossRef]
     [Google Scholar]
  28. Kol M. A., van Dalen A., de Kruijff B., de Kroon A. I. 2003; Translocation of phospholipids is facilitated by a subset of membrane-spanning proteins of the bacterial cytoplasmic membrane. J Biol Chem 278:24586–24593 [CrossRef]
     [Google Scholar]
  29. Kol M. A., de Kroon A. I., Killian J. A., de Kruijff B. 2004; Transbilayer movement of phospholipids in biogenic membranes. Biochemistry 43:2673–2681 [CrossRef]
     [Google Scholar]
  30. Koo S. P., Bayer A. S., Sahl H. G., Proctor R. A., Yeaman M. R. 1996a; Staphylocidal action of thrombin-induced platelet microbicidal protein is not solely dependent on transmembrane potential. Infect Immun 64:1070–1074
     [Google Scholar]
  31. Koo S. P., Yeaman M. R., Bayer A. S. 1996b; Staphylocidal action of thrombin-induced platelet microbicidal protein is influenced by microenvironment and target cell growth phase. Infect Immun 64:3758–3764
     [Google Scholar]
  32. Koo S. P., Yeaman M. R., Nast C. C., Bayer A. S. 1997; The cytoplasmic membrane is a primary target for the staphylocidal action of thrombin-induced platelet microbicidal protein. Infect Immun 65:4795–4800
     [Google Scholar]
  33. Koo S.-P., Kagan B. L., Bayer A. S., Yeaman M. R. 1999; Membrane permeabilization by thrombin-induced platelet microbicidal protein-1 is modulated by transmembrane voltage orientation and magnitude. Infect Immun 67:2475–2481
     [Google Scholar]
  34. Koo S.-P., Bayer A. S., Yeaman M. R. 2001; Diversity in antistaphylococcal mechanisms among membrane-targeting antimicrobial peptides. Infect Immun 69:4916–4922 [CrossRef]
     [Google Scholar]
  35. Koprivnjak T., Peschel A., Gelb M. H., Liang N. S., Weiss J. P. 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 [CrossRef]
     [Google Scholar]
  36. Kristian S. A., Lauth X., Nizet V., Goetz F., Neumeister B., Peschel A., Landmann R. 2003; Alanylation of teichoic acids protects Staphylococcus aureus against Toll-like receptor 2-dependent host defense in a mouse tissue cage infection model. J Infect Dis 188:414–423 [CrossRef]
     [Google Scholar]
  37. Kupferwasser L. I., Skurray R. A., Brown M. H., Firth N., Yeaman M. R., Bayer A. S. 1999; Plasmid-mediated resistance to thrombin-induced platelet microbicidal protein in staphylococci: role of the qacA locus. Antimicrob Agents Chemother 43:2395–2399
     [Google Scholar]
  38. Kupferwasser L. I., Yeaman M. R., Shapiro S. M., Nast C. C., Bayer A. S. 2002; In vitro susceptibility to thrombin-induced platelet microbicidal protein is associated with reduced disease progression and complication rates in experimental Staphylococcus aureus endocarditis: microbiological, histopathologic, and echocardiographic analyses. Circulation 105:746–752 [CrossRef]
     [Google Scholar]
  39. Lentz B. R. 2003; Exposure of platelet membrane phosphatidylserine regulates blood coagulation. Prog Lipid Res 42:423–438 [CrossRef]
     [Google Scholar]
  40. Lohner K., Blondelle S. E. 2005; Molecular mechanisms of membrane perturbation by antimicrobial peptides and the use of biophysical studies in the design of novel peptide antibiotics. Comb Chem High Throughput Screen 8:241–256 [CrossRef]
     [Google Scholar]
  41. Margolles A., Putman M., van Veen H. W., Konings W. N. 1999; The purified and functionally reconstituted multidrug transporter LmrA of Lactococcus lactis mediates the transbilayer movement of specific fluorescent phospholipids. Biochemistry 38:16298–16306 [CrossRef]
     [Google Scholar]
  42. McIntyre J. C., Sleight R. G. 1991; Fluorescence assay for phospholipid membrane asymmetry. Biochemistry 30:11819–11827 [CrossRef]
     [Google Scholar]
  43. Moore R. A., Bates N. C., Hancock R. E. 1986; Interaction of polycationic antibiotics with Pseudomonas aeruginosa lipopolysaccharide and lipid A studied by using dansyl-polymyxin. Antimicrob Agents Chemother 29:496–500 [CrossRef]
     [Google Scholar]
  44. Nishi H., Komatsuzawa H., Fujiwara T., McCallum N., Sugai M. 2004; Reduced content of lysyl-phosphatidylglycerol in the cytoplasmic membrane affects susceptibility to moenomycin, as well as vancomycin, gentamicin, and antimicrobial peptides, in Staphylococcus aureus . Antimicrob Agents Chemother 48:4800–4807 [CrossRef]
     [Google Scholar]
  45. Peschel A. 2002; How do bacteria resist human antimicrobial peptides?. Trends Microbiol 10:179–186 [CrossRef]
     [Google Scholar]
  46. Peschel A., Otto M., Jack R. W., Kalbacher H., Jung G., Gotz F. 1999; Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem 274:8405–8410 [CrossRef]
     [Google Scholar]
  47. Peschel A., Jack R. W., Otto M., Collins L. V., Staubitz P., Nicholson G., Kalbacher H., Nieuwenhuizen W. F., Jung G. & other authors 2001; Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. J Exp Med 193:1067–1076 [CrossRef]
     [Google Scholar]
  48. Petit J. M., Maftah A., Ratinaud M. H., Julien R. 1992; 10N-nonyl acridine orange interacts with cardiolipin and allows the quantification of this phospholipid in isolated mitochondria. Eur J Biochem 209:267–273 [CrossRef]
     [Google Scholar]
  49. Petit J. M., Huet O., Gallet P. F., Maftah A., Ratinaud M. H., Julien R. 1994; Direct analysis and significance of cardiolipin transverse distribution in mitochondrial inner membranes. Eur J Biochem 220:871–879 [CrossRef]
     [Google Scholar]
  50. Pokorny A., Almeida P. F. 2005; Permeabilization of raft-containing lipid vesicles by delta-lysin: a mechanism for cell sensitivity to cytotoxic peptides. Biochemistry 44:9538–9544 [CrossRef]
     [Google Scholar]
  51. Polissi A., Georgopoulos C. 1996; Mutational analysis and properties of the msbA gene of Escherichia coli , coding for an essential ABC family transporter. Mol Microbiol 20:1221–1233 [CrossRef]
     [Google Scholar]
  52. Pomorski T., Muller P., Zimmermann B., Burger K., Devaux P. F., Herrmann A. 1996; Transbilayer movement of fluorescent and spin-labeled phospholipids in the plasma membrane of human fibroblasts: a quantitative approach. J Cell Sci 109:687–698
     [Google Scholar]
  53. Pomorski T., Holthuis J. C., Herrmann A., van Meer G. 2004; Tracking down lipid flippases and their biological functions. J Cell Sci 117:805–813 [CrossRef]
     [Google Scholar]
  54. Reyes C. L., Chang G. 2005; Structure of the ABC transporter MsbA in complex with ADP.vanadate and lipopolysaccharide. Science 308:1028–1031 [CrossRef]
     [Google Scholar]
  55. Rossetti F. F., Reviakine I., Assi F., Textor M., Csúcs G., Vörös J. 2004; Interaction of poly(l-lysine)-g-poly(ethylene glycol) with supported phospholipid bilayers. Biophys J 87:1711–1721 [CrossRef]
     [Google Scholar]
  56. Satchell D. P., Sheynis T., Shirafuji Y., Kolusheva S., Ouellette A. J., Jelinek R. 2003; Interactions of mouse Paneth cell α -defensins and α -defensin precursors with membranes. Prosegment inhibition of peptide association with biomimetic membranes. J Biol Chem 278:13838–13846 [CrossRef]
     [Google Scholar]
  57. Takemura H., Kaku M., Kohno S., Hirakata Y., Tanaka H., Yoshida R., Tomono K., Koga H., Wada A. & other authors 1996; Evaluation of susceptibility of gram-positive and -negative bacteria to human defensins by using radial diffusion assay. Antimicrob Agents Chemother 40:2280–2284
     [Google Scholar]
  58. Tannert A., Pohl A., Pomorski T., Herrmann A. 2003; Protein-mediated transbilayer movement of lipids in eukaryotes and prokaryotes: the relevance of ABC transporters. Int J Antimicrob Agents 22:177–187 [CrossRef]
     [Google Scholar]
  59. Wu T., Yeaman M. R., Bayer A. S. 1994; In vitro resistance to platelet microbicidal protein correlates with endocarditis source among bacteremic staphylococcal and streptococcal isolates. Antimicrob Agents Chemother 38:729–732 [CrossRef]
     [Google Scholar]
  60. Xiong Y. Q., Yeaman M. R., Bayer A. S. 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
     [Google Scholar]
  61. Xiong Y. Q., Bayer A. S., Yeaman M. R. 2002; Inhibition of intracellular macromolecular synthesis in Staphylococcus aureus by thrombin-induced platelet microbicidal proteins. J Infect Dis 185:348–356 [CrossRef]
     [Google Scholar]
  62. Xiong Y. Q., Mukhopadhyay K., Yeaman M. R., Adler-Moore J., Bayer A. S. 2005; Functional interrelationships between cell membrane and cell wall in antimicrobial peptide-mediated killing of Staphylococcus aureus . Antimicrob Agents Chemother 49:3114–3121 [CrossRef]
     [Google Scholar]
  63. Xiong Y. Q., Bayer A. S., Elazegui L., Yeaman M. R. 2006; A synthetic congener modeled on a microbicidal domain of thrombin-induced platelet microbicidal protein-1 recapitulates staphylocidal mechanisms of the native molecule. Antimicrob Agents Chemother 50:3786–3792 [CrossRef]
     [Google Scholar]
  64. Yeaman M. R. 1997; The role of platelets in antimicrobial host defense. Clin Infect Dis 25:951–968 [CrossRef]
     [Google Scholar]
  65. Yeaman M. R., Yount N. Y. 2003; Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55:27–55 [CrossRef]
     [Google Scholar]
  66. Yeaman M. R., Sullam P. M., Dazin P. F., Bayer A. S. 1994; Platelet microbicidal protein alone and in combination with antibiotics reduces Staphylococcus aureus adherence to platelets in vitro. Infect Immun 62:3416–3423
     [Google Scholar]
  67. Yeaman M. R., Tang Y. Q., Shen A. J., Bayer A. S., Selsted M. E. 1997; Purification and in vitro activities of rabbit platelet microbicidal proteins. Infect Immun 65:1023–1031
     [Google Scholar]
  68. Yeaman M. R., Bayer A. S., Koo S. P., Foss W., Sullam P. M. 1998; Platelet microbicidal proteins and neutrophil defensin disrupt the Staphylococcus aureus cytoplasmic membrane by distinct mechanisms of action. J Clin Invest 101:178–187 [CrossRef]
     [Google Scholar]
  69. Yeaman M. R., Gank K. D., Bayer A. S., Brass E. P. 2002; Synthetic peptides that exert antimicrobial activities in whole blood and blood-derived matrices. Antimicrob Agents Chemother 46:3883–3891 [CrossRef]
     [Google Scholar]
  70. Yount N. Y., Gank K. D., Xiong Y. Q., Bayer A. S., Pender T., Welch W. H., Yeaman M. R. 2004; Platelet microbicidal protein 1: structural themes of a multifunctional antimicrobial peptide. Antimicrob Agents Chemother 48:4395–4404 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2006/003111-0
Loading
In vitro susceptibility of Staphylococcus aureus to thrombin-induced platelet microbicidal protein-1 (tPMP-1) is influenced by cell membrane phospholipid composition and asymmetry
Microbiology 153, 1187 (2007); https://doi.org/10.1099/mic.0.2006/003111-0
/content/journal/micro/10.1099/mic.0.2006/003111-0
/content/journal/micro/10.1099/mic.0.2006/003111-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error