Participation of Bacterial Lipases, Sphingomyelinases, and Phospholipases in Gram-Positive Bacterial Pathogenesis

  • Howard GoldfineEmail author
Living reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)


A growing number of both Gram-positive and Gram-negative bacteria are now known to produce lipases, sphingomyelinases, and phospholipases, and many of these enzymes have been shown to be involved in bacterial pathogenesis. In this review, lipases, sphingomyelinases, and phospholipases from Gram-positive bacteria are described and their roles in furthering the entry into and growth within host cells and tissues are discussed. The importance of phospholipases and sphingomyelinases in infections caused by Clostridium perfringens and Listeria monocytogenes have been demonstrated by many studies on the wild type and mutant forms of these enzymes. The significance of lipases, sphingomyelinases, and phospholipases for other infectious organisms including Staphylococcus aureus, Bacillus anthracis, and Mycobacterium tuberculosis is also discussed.


  1. Alberti-Segui C, Goeden KR, Higgins DE (2007) Differential function of Listeria monocytogenes listeriolysin O and phospholipases C in vacuolar dissolution following cell-to-cell spread. Cell Microbiol 9:179–195PubMedCrossRefGoogle Scholar
  2. Awad MM, Bryant AE, Stevens DL, Rood JI (1995) Virulence studies on chromosomal alpha-toxin and theta-toxin mutants constructed by allelic exchange provide genetic evidence for the essential role of alpha-toxin in Clostridium perfringens-mediated gas gangrene. Mol Microbiol 15:191–202PubMedCrossRefGoogle Scholar
  3. Birmingham CL, Canadieni V, Gouin E, Troy EB, Yoshimori T, Cossart P, Higgins DE, Brumell JH (2007) Listeria monocytogenes evades killing by autophagy during colonization of host cells. Autophagy 3:442–451PubMedCrossRefGoogle Scholar
  4. Birmingham CL, Canadien V, Kaniuk NA, Steinberg BE, Higgins DE, Brumell JH (2008) Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles. Nature 451:350–U13PubMedCrossRefGoogle Scholar
  5. Bryant AE, Chen RYZ, Nagata Y, Wang Y, Lee CH, Finegold S, Guth PH, Stevens DL (2000) Clostridial gas gangrene. I. Cellular and molecular mechanisms of microvascular dysfunction induced by exotoxins of Clostridium perfringens. J Infect Dis 182:799–807PubMedCrossRefGoogle Scholar
  6. Callegan MC, Cochran DC, Kane ST, Gilmore MS, Gominet M, Lereclus D (2002a) Contribution of membrane-damaging toxins to Bacillus endophthalmitis pathogenesis. Infect Immun 70:5381–5389PubMedPubMedCentralCrossRefGoogle Scholar
  7. Callegan MC, Kane ST, Cochran DC, Gilmore MS (2002b) Molecular mechanisms of Bacillus endophthalmitis pathogenesis. DNA Cell Biol 21:367–373PubMedCrossRefPubMedCentralGoogle Scholar
  8. Camilli A, Goldfine H, Portnoy DA (1991) Listeria monocytogenes mutants lacking phosphatidylinositol-specific phospholipase C are avirulent. J Exp Med 173:751–754PubMedCrossRefGoogle Scholar
  9. Camilli A, Tilney LG, Portnoy DA (1993) Dual roles of plcA in Listeria monocytogenes pathogenesis. Mol Microbiol 8:143–157PubMedPubMedCentralCrossRefGoogle Scholar
  10. Chen W, Goldfine H, Ananthanarayanan B, Cho W, Roberts MF (2009) Listeria monocytogenes phosphatidylinositol-specific phospholipase C: kinetic activation and homing in on different interfaces. Biochemistry 48:3578–3592PubMedPubMedCentralCrossRefGoogle Scholar
  11. Dedieu L, Serveau-Avesque C, Canaan S (2013) Identification of residues involved in substrate specificity and cytotoxicity of two closely related Cutinases from Mycobacterium tuberculosis. PLoS One 8:e66913PubMedPubMedCentralCrossRefGoogle Scholar
  12. Deretic V, Saitoh T, Akira S (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13:722–737PubMedPubMedCentralCrossRefGoogle Scholar
  13. Flores-Diaz M, Alape-Giron A (2003) Role of Clostridium perfringens phospholipase C in the pathogenesis of gas gangrene. Toxicon 42:979–986PubMedCrossRefPubMedCentralGoogle Scholar
  14. Flores-Diaz M, Alape-Giron A, Clark G, Catimel B, Hirabayashi Y, Nice E, Gutierrez JM, Titball R (2005) A cellular deficiency of gangliosides causes hypersensitivity to Clostridium perfringens phospholipase C. J Biol Chem 280:26680–26689PubMedCrossRefPubMedCentralGoogle Scholar
  15. Flores-Diaz M, Monturiol-Gross L, Naylor C, Alape-Giron A, Flieger A (2016) Bacterial sphingomyelinases and phospholipases as virulence factors. Microbiol Mol Biol Rev 80:597–628PubMedPubMedCentralCrossRefGoogle Scholar
  16. Forster BM, Bitar AP, Slepkov ER, Kota KJ, Sondermann H, Marquis H (2011) The metalloprotease of Listeria monocytogenes is regulated by pH. J Bacteriol 193:5090–5097PubMedPubMedCentralCrossRefGoogle Scholar
  17. Freitag NE, Rong L, Portnoy DA (1993) Regulation of the prfA transcriptional activator of Listeria monocytogenes: multiple promoter elements contribute to intracellular growth and cell-to-cell spread. Infect Immun 61:2537–2544PubMedPubMedCentralGoogle Scholar
  18. Gaillard JL, Berche P, Sansonetti P (1986) Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes. Infect Immun 52:50–55PubMedPubMedCentralGoogle Scholar
  19. Gaillard J-L, Berche P, Mounier J, Richard S, Sansonetti P (1987) In vitro model of penetration and intracellular growth of Listeria monocytogenes in the human enterocyte-like cell line Caco-2. Infect Immun 55:2822–2829PubMedPubMedCentralGoogle Scholar
  20. Gandhi AJ, Perussia B, Goldfine H (1993) Listeria monocytogenes phosphatidylinositol (PI)-specific phospholipase C has low activity on glycosyl-PI anchored proteins. J Bacteriol 175:8014–8017PubMedPubMedCentralCrossRefGoogle Scholar
  21. Geoffroy C, Raveneau J, Beretti J-L, Lecroisey A, Vazquez-Boland J-A, Alouf JE, Berche P (1991) Purification and characterization of an extracellular 29-kilodalton phospholipase C. From Listeria monocytogenes. Infect Immun 59:2382–2388PubMedPubMedCentralGoogle Scholar
  22. Giese B, Glowinski F, Paprotka K, Dittmann S, Steiner T, Sinha B, Fraunholz MJ (2011) Expression of delta-toxin by Staphylococcus aureus mediates escape from phago-endosomes of human epithelial and endothelial cells in the presence of beta-toxin. Cell Microbiol 13:316–329PubMedCrossRefGoogle Scholar
  23. Goldfine H, Knob C (1992) Purification and characterization of Listeria monocytogenes phosphatidylinositol-specific phospholipase C. Infect Immun 60:4059–4067PubMedPubMedCentralGoogle Scholar
  24. Goldfine H, Marquis H (2007) Escape of Listeria monocytogenes from a vacuole. In: Goldfine H, Shen H (eds) Listeria monocytogenes: pathogenesis and host response. Springer, New YorkCrossRefGoogle Scholar
  25. Goni FM, Montes LR, Alonso A (2012) Phospholipases C and sphingomyelinases: lipids as substrates and modulators of enzyme activity. Prog Lipid Res 51:238–266PubMedCrossRefGoogle Scholar
  26. Gonzalez-Zorn B, Dominguez-Bernal G, Suarez M, Ripio MT, Vega Y, Novella S, Rodriguez A, Chico I, Tierrez A, Vazquez-Boland JA (2000) SmcL, a novel membrane-damaging virulence factor in Listeria. Int J Med Microbiol 290:369–374PubMedCrossRefGoogle Scholar
  27. Heffernan BJ, Thomason B, Herring-Palmer A, Shaughnessy L, McDonald R, Fisher N, Huffnagle GB, Hanna P (2006) Bacillus anthracis phospholipases C facilitate macrophage-associated growth and contribute to virulence in a murine model of inhalation anthrax. Infect Immun 74:3756–3764PubMedPubMedCentralCrossRefGoogle Scholar
  28. Heffernan BJ, Thomason B, Herring-Palmer A, Hanna P (2007) Bacillus anthracis anthrolysin O and three phospholipases C are functionally redundant in a murine model of inhalation anthrax. FEMS Microbiol Lett 271:98–105PubMedCrossRefGoogle Scholar
  29. Heinz DW, Ryan M, Smith MP, Weaver LH, Keana JFW, Griffith OH (1996) Crystal structure of phosphatidylinositol-specific phospholipase C from Bacillus cereus in complex with glucosaminyl(α1-->6)-D- myo-inositol, an essential fragment of GPI anchors. Biochemistry 35:9496–9504PubMedCrossRefPubMedCentralGoogle Scholar
  30. Huang Q, Gershenson A, Roberts MF (2016) Recombinant broad-range phospholipase C from Listeria monocytogenes exhibits optimal activity at acidic pH. Biochim Biophys Acta 1864:697–705PubMedPubMedCentralCrossRefGoogle Scholar
  31. Huseby M, Shi K, Brown CK, Digre J, Mengistu F, Seo KS, Bohach GA, Schlievert PM, Ohlendorf DH, Earhart CA (2007) Structure and biological activities of beta toxin from Staphylococcus aureus. J Bacteriol 189:8719–8726PubMedPubMedCentralCrossRefGoogle Scholar
  32. Huseby MJ, Kruse AC, Digre J, Kohler PL, Vocke JA, Mann EE, Bayles KW, Bohach GA, Schlievert PM, Ohlendorf DH, Earhart CA (2010) Beta toxin catalyzes formation of nucleoprotein matrix in staphylococcal biofilms. Proc Natl Acad Sci U S A 107:14407–14412PubMedPubMedCentralCrossRefGoogle Scholar
  33. Ikezawa H, Yamanegi M, Taguchi R, Miyashita T, Ohyabu T (1976) Studies on phosphatidylinositol phosphodiesterase (phospholipase C type) of Bacillus cereus I Purification, properties and phosphatase-releasing activity. Biochim Biophys Acta 450:154–164PubMedCrossRefGoogle Scholar
  34. Johansen KA, Gill RE, Vasil ML (1996) Biochemical and molecular analysis of phospholipase C and phospholipase D activity in mycobacteria. Infect Immun 64:3259–3266PubMedPubMedCentralGoogle Scholar
  35. Johnson G (2017) The alpha/beta hydrolase fold proteins of Mycobacterium tuberculosis, with reference to their contribution to virulence. Curr Protein Pept Sci 18:190–210PubMedCrossRefGoogle Scholar
  36. Kathariou S, Metz P, Hof H, Goebel W (1987) Tn916-induced mutations in the hemolysin determinant affecting virulence of Listeria monocytogenes. J Bacteriol 169:1291–1297PubMedPubMedCentralCrossRefGoogle Scholar
  37. Klichko VI, Miller J, Wu A, Popov SG, Alibek K (2003) Anaerobic induction of Bacillus anthracis hemolytic activity. Biochem Biophys Res Commun 303:855–862PubMedCrossRefGoogle Scholar
  38. Lam GY, Fattouh R, Muise AM, Grinstein S, Higgins DE, Brumell JH (2011) Listeriolysin O suppresses phospholipase C-mediated activation of the Microbicidal NADPH oxidase to promote Listeria monocytogenes infection. Cell Host Microbe 10:627–634PubMedPubMedCentralCrossRefGoogle Scholar
  39. Le Chevalier F, Cascioferro A, Frigui W, Pawlik A, Boritsch EC, Bottai D, Majlessi L, Herrmann JL, Brosch R (2015) Revisiting the role of phospholipases C in virulence and the lifecycle of Mycobacterium tuberculosis. Sci Rep 5:16918PubMedPubMedCentralCrossRefGoogle Scholar
  40. Leimeister-Wächter M, Haffner C, Domann E, Goebel W, Chakraborty T (1990) Identification of a gene that positively regulates expression of listeriolysin, the major virulence factor of Listeria monocytogenes. Proc Natl Acad Sci U S A 87:8336–8340PubMedPubMedCentralCrossRefGoogle Scholar
  41. Leimeister-Wächter M, Domann E, Chakraborty T (1991) Detection of a gene encoding a phosphatidylinositol specific phospholipase C that is co-ordinately expressed with listeriolysin in Listeria monocytogenes. Mol Microbiol 5:361–366PubMedCrossRefPubMedCentralGoogle Scholar
  42. Lorber B (2007) Listeriosis. In: Goldfine H, Shen H (eds) Listeria monocytogenes: pathogenesis and host response. Springer, New YorkGoogle Scholar
  43. Low MG, Finean JB (1977) Release of alkaline phosphatase from membranes by a phosphatidylinositol-specific phospholipase C. Biochem J 167:281–284PubMedPubMedCentralCrossRefGoogle Scholar
  44. Macfarlane MG, Knight BCJG (1941) The biochemistry of bacterial toxins. I The lecithinase activity of Cl welchii toxins. Biochem J 35:884PubMedPubMedCentralCrossRefGoogle Scholar
  45. Marquis H, Doshi V, Portnoy DA (1995) Broad range phospholipase C and metalloprotease mediate Listeriolysin O-independent escape of Listeria monocytogenes from a primary vacuole in human epithelial cells. Infect Immun 63:4531–4534PubMedPubMedCentralGoogle Scholar
  46. Marquis H, Hager EJ (2000) pH-regulated activation and release of a bacteria-associated phospholipase C during intracellular infection by Listeria monocytogenes. Mol Microbiol 35:289–298PubMedPubMedCentralCrossRefGoogle Scholar
  47. Mengaud J, Braun-Breton C, Cossart P (1991a) Identification of phosphatidylinositol-specific phospholipase C activity in Listeria monocytogenes: a novel type of virulence factor. Mol Microbiol 5:367–372PubMedCrossRefPubMedCentralGoogle Scholar
  48. Mengaud J, Dramsi S, Gouin E, Vazquez-Boland J-A, Milon G, Cossart P (1991b) Pleiotropic control of Listeria monocytogenes virulence factors by a gene that is autoregulated. Mol Microbiol 5:2273–2283PubMedCrossRefPubMedCentralGoogle Scholar
  49. Miner MD, Port GC, Freitag NE (2007) Regulation of Listeria monocytogenes virulence genes. In: Goldfine H, Shen H (eds) Listeria monocytogenes: pathogenesis and host response. Springer, New YorkGoogle Scholar
  50. Mitchell G, Ge L, Huang QY, Chen C, Kianian S, Roberts MF, Schekman R, Portnoy DA (2015) Avoidance of autophagy mediated by PlcA or ActA is required for Listeria monocytogenes growth in macrophages. Infect Immun 83:2175–2184PubMedPubMedCentralCrossRefGoogle Scholar
  51. Mitchell G, Cheng MI, Chen C, Nguyen BN, Whiteley AT, Kianian S, Cox JS, Green DR, McDonald KL, Portnoy DA (2018) Listeria monocytogenes triggers noncanonical autophagy upon phagocytosis, but avoids subsequent growth-restricting xenophagy. Proc Natl Acad Sci U S A 115:E210–E217PubMedCrossRefPubMedCentralGoogle Scholar
  52. Monturiol-Gross L, Flores-Diaz M, Pineda-Padilla MJ, Castro-Castro AC, Alape-Giron A (2014) Clostridium perfringens phospholipase C induced ROS production and cytotoxicity require PKC, MEK1 and NF kappa B activation. PLoS One 9:e86475PubMedPubMedCentralCrossRefGoogle Scholar
  53. Moser J, Gerstel B, Meyer JEW, Chakraborty T, Wehland J, Heinz DW (1997) Crystal structure of the phosphatidylinositol-specific phospholipase C from the human pathogen Listeria monocytogenes. J Mol Biol 273:269–282PubMedCrossRefPubMedCentralGoogle Scholar
  54. O’Brien DK, Melville SB (2004) Effects of Clostridium perfringens alpha-toxin (PLC) and perfringolysin O (PFO) on cytotoxicity to macrophages, on escape from the phagosomes of macrophages, and on persistence of C-perfringens in host tissues. Infect Immun 72:5204–5215PubMedPubMedCentralCrossRefGoogle Scholar
  55. Ochi S, Miyawaki T, Matsuda H, Oda M, Nagahama M, Sakurai J (2002) Clostridium perfringens alpha-toxin induces rabbit neutrophil adhesion. Microbiology-Sgm 148:237–245CrossRefGoogle Scholar
  56. Oda M, Hashimoto M, Takahashi M, Ohmae Y, Seike S, Kato R, Fujita A, Tsuge H, Nagahama M, Ochi S, Sasahara T, Hayashi S, Hirai Y, Sakurai J (2012a) Role of sphingomyelinase in infectious diseases caused by Bacillus cereus. PLoS One 7:e38054PubMedPubMedCentralCrossRefGoogle Scholar
  57. Oda M, Shiihara R, Ohmae Y, Kabura M, Takagishi T, Kobayashi K, Nagahama M, Inoue M, Abe T, Setsu K, Sakurai J (2012b) Clostridium perfringens alpha-toxin induces the release of IL-8 through a dual pathway via TrkA in A549 cells. BBA-Mol Basis Dis 1822:1581–1589CrossRefGoogle Scholar
  58. Oda M, Imagawa H, Kato R, Yabiku K, Yoshikawa T, Takemoto T, Takahashi H, Yamamoto H, Nishizawa M, Sakurai J, Nagahama M (2014) Novel inhibitor of bacterial sphingomyelinase, SMY-540, developed based on three-dimensional structure analysis. J Enzyme Inhib Med Chem 29:303–310PubMedCrossRefPubMedCentralGoogle Scholar
  59. Paulick MG, Bertozzi CR (2008) The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins. Biochemistry 47:6991–7000PubMedPubMedCentralCrossRefGoogle Scholar
  60. Portnoy DA, Jacks PS, Hinrichs DJ (1988) Role of hemolysin for the intracellular growth of Listeria monocytogenes. J Exp Med 167:1459–1471PubMedCrossRefPubMedCentralGoogle Scholar
  61. Poussin MA, Leitges M, Goldfine H (2009) The ability of Listeria monocytogenes PI-PLC to facilitate escape from the macrophage phagosome is dependent on host PKC beta. Microb Pathog 46:1–5PubMedCrossRefGoogle Scholar
  62. Poyart C, Abachin E, Razafimanantsoa I, Berche P (1993) The zinc metalloprotease of Listeria monocytogenes is required for maturation of phosphatidylcholine phospholipase C: direct evidence obtained by gene complementation. Infect Immun 61:1576–1580PubMedPubMedCentralGoogle Scholar
  63. Py BF, Lipinski MM, Yuan JY (2007) Autophagy limits Listeria monocytogenes intracellular growth in the early phase of primary infection. Autophagy 3:117–125PubMedCrossRefGoogle Scholar
  64. Radoshevich L, Cossart P (2018) Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis. Nat Rev Microbiol 16:32–46PubMedCrossRefGoogle Scholar
  65. Raynaud C, Guilhot C, Rauzier J, Bordat Y, Pelicic V, Manganelli R, Smith I, Gicquel B, Jackson M (2002) Phospholipases C are involved in the virulence of Mycobacterium tuberculosis. Mol Microbiol 45:203–217PubMedCrossRefGoogle Scholar
  66. Read TD, Peterson SN, Tourasse N, Baillie LW, Paulsen IT, Nelson KE, Tettelin H, Fouts DE, Eisen JA, Gill SR, Holtzapple EK, Okstad OA, Helgason E, Rilstone J, Wu M, Kolonay JF, Beanan MJ, Dodson RJ, Brinkac LM, Gwinn M, Deboy RT, Madpu R, Daugherty SC, Durkin AS, Haft DH, Nelson WC, Peterson JD, Pop M, Khouri HM, Radune D, Benton JL, Mahamoud Y, Jiang LX, Hance IR, Weidman JF, Berry KJ, Plaut RD, Wolf AM, Watkins KL, Nierman WC, Hazen A, Cline R, Redmond C, Thwaite JE, White O, Salzberg SL, Thomason B, Friedlander AM, Koehler TM, Hanna PC, Kolsto AB, Fraser CM (2003) The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria. Nature 423:81–86PubMedCrossRefGoogle Scholar
  67. Rezanka T, Padrova K, Sigler K (2017) Regioisomeric and enantiomeric analysis of triacylglycerols. Anal Biochem 524:3–12PubMedCrossRefGoogle Scholar
  68. Rich KA, Burkett C, Webster P (2003) Cytoplasmic bacteria can be targets for autophagy. Cell Microbiol 5:455–468PubMedCrossRefGoogle Scholar
  69. Roberts MF, Khan HM, Goldstein R, Reuter N, Gershenson A (2018) Search and subvert: minimalist bacterial phosphatidylinositol-specific phospholipase C enzymes. Chem Rev 118:8435–8473PubMedCrossRefGoogle Scholar
  70. Schlüter D, Domann E, Buck C, Hain T, Hof H, Chakraborty T, Deckert-Schlüter M (1998) Phosphatidylcholine-specific phospholipase c from Listeria monocytogenes is an important virulence factor in murine cerebral listeriosis. Infect Immun 66:5930–5938PubMedPubMedCentralGoogle Scholar
  71. Schue M, Maurin D, Dhouib R, N'goma JCB, Delorme V, Lambeau G, Carriere F, Canaan S (2010) Two cutinase-like proteins secreted by Mycobacterium tuberculosis show very different lipolytic activities reflecting their physiological function. FASEB J 24:1893–1903PubMedCrossRefGoogle Scholar
  72. Schwarzer N, Nöst R, Seybold J, Parida SK, Fuhrmann O, Krüll M, Schmidt R, Newton R, Hippenstiel S, Domann E, Chakraborty T, Suttorp N (1998) Two distinct phospholipases C of Listeria monocytogenes induce ceramide generation, nuclear factor-kappaB activation, and E- selectin expression in human endothelial cells. J Immunol 161:3010–3018PubMedGoogle Scholar
  73. Shannon JG, Ross CL, Koehler TM, Rest RF (2003) Characterization of anthrolysin O, the Bacillus anthracis cholesterol-dependent cytolysin. Infect Immun 71:3183–3189PubMedPubMedCentralCrossRefGoogle Scholar
  74. Sibelius U, Chakraborty T, Krögel B, Wolf J, Rose F, Schmidt R, Wehland J, Seeger W, Grimminger F (1996) The listerial exotoxins listeriolysin and phosphatidylinositol- specific phospholipase C synergize to elicit endothelial cell phosphoinositide metabolism. J Immunol 157:4055–4060PubMedGoogle Scholar
  75. Sibelius U, Schulz EC, Rose F, Hattar K, Jacobs T, Weiss S, Chakraborty T, Seeger W, Grimminger F (1999) Role of Listeria monocytogenes exotoxins listeriolysin and phosphatidylinositol-specific phospholipase C in activation of human neutrophils. Infect Immun 67:1125–1130PubMedPubMedCentralGoogle Scholar
  76. Smith GA, Marquis H, Jones S, Johnston NC, Portnoy DA, Goldfine H (1995) The two distinct phospholipases C of Listeria monocytogenes have overlapping roles in escape from a vacuole and cell-to-cell spread. Infect Immun 63:4231–4237PubMedPubMedCentralGoogle Scholar
  77. Stevens DL, Titball RW, Jepson M, Bayer CR, Hayes-Schroer SM, Bryant AE (2004) Immunization with the C-domain of alpha -toxin prevents lethal infection, localizes tissue injury, and promotes host response to challenge with Clostridium perfringens. J Infect Dis 190:767–773PubMedCrossRefGoogle Scholar
  78. Stonehouse MJ, Cota-Gomez A, Parker SK, Martin WE, Hankin JA, Murphy RC, Chen WB, Lim KB, Hackett M, Vasil AI, Vasil ML (2002) A novel class of microbial phosphocholine-specific phospholipases C. Mol Microbiol 46:661–676PubMedCrossRefGoogle Scholar
  79. Tajima A, Iwase T, Shinji H, Seki K, Mizunoe Y (2009) Inhibition of endothelial Interleukin-8 production and neutrophil transmigration by Staphylococcus aureus Beta-Hemolysin. Infect Immun 77:327–334PubMedCrossRefGoogle Scholar
  80. Takagishi T, Takehara M, Seike S, Miyamoto K, Kobayashi K, Nagahama M (2017) Clostridium perfringens alpha-toxin impairs erythropoiesis by inhibition of erythroid differentiation. Sci Rep 7:11CrossRefGoogle Scholar
  81. Tattoli I, Sorbara MT, Yang C, Tooze SA, Philpott DJ, Girardin SE (2013) Listeria phospholipases subvert host autophagic defenses by stalling pre-autophagosomal structures. EMBO J 32:3066–3078PubMedPubMedCentralCrossRefGoogle Scholar
  82. Tilney LG, Portnoy DA (1989) Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes. J Cell Biol 109:1597–1608PubMedCrossRefPubMedCentralGoogle Scholar
  83. Urbina P, Collado MI, Alonso A, Goni FM, Flores-Diaz M, Alape-Giron A, Ruysschaert JM, Lensink MF (2011) Unexpected wide substrate specificity of C. perfringens alpha-toxin phospholipase C. BBA-Biomembranes 1808:2618–2627PubMedCrossRefPubMedCentralGoogle Scholar
  84. Vázquez-Boland JA, Kuhn M, Berche P, Chakraborty T, Domínguez-Bernal G, Goebel W, González-Zorn B, Wehland J, Kreft J (2001) Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev 14:584–640PubMedPubMedCentralCrossRefGoogle Scholar
  85. Volwerk JJ, Wetherwax PB, Evans LM, Kuppe A, Griffith OH (1989) Phosphatidylinositol-specific phospholipase C from Bacillus cereus: improved purification, amino acid composition, and amino terminal sequence. J Cell Biochem 39:315–325PubMedCrossRefPubMedCentralGoogle Scholar
  86. Wadsworth SJ, Goldfine H (1999) Listeria monocytogenes phospholipase C-dependent calcium signaling modulates bacterial entry into J774 macrophage-like cells. Infect Immun 67:1770–1778PubMedPubMedCentralGoogle Scholar
  87. Wadsworth SJ, Goldfine H (2002) Mobilization of protein kinase C in macrophages induced by Listeria monocytogenes affects its internalization and escape from the phagosome. Infect Immun 70:4650–4660PubMedPubMedCentralCrossRefGoogle Scholar
  88. Wei Z, Schnupf P, Poussin MA, Zenewicz LA, Shen H, Goldfine H (2005a) Characterization of Listeria monocytogenes expressing anthrolysin O and phosphatidylinositol-specific phospholipase C from Bacillus anthracis. Infect Immun 73:6639–6646PubMedPubMedCentralCrossRefGoogle Scholar
  89. Wei Z, Zenewicz LA, Goldfine H (2005b) Listeria monocytogenes phosphatidylinositol-specific phospholipase C has evolved for virulence by greatly reduced activity of GPI anchors. Proc Natl Acad Sci U S A 102:12927–12931PubMedPubMedCentralCrossRefGoogle Scholar
  90. Yeung PSM, Zagorski N, Marquis H (2005) The metalloprotease of Listeria monocytogenes controls cell wall translocation of the broad-range phospholipase c. J Bacteriol 187:2601–2608PubMedPubMedCentralCrossRefGoogle Scholar
  91. Yeung PSM, Na YJ, Kreuder AJ, Marquis H (2007) Compartmentalization of the broad-range phospholipase C activity to the spreading vacuole is critical for Listeria monocytogenes virulence. Infect Immun 75:44–51PubMedCrossRefPubMedCentralGoogle Scholar
  92. Zenewicz LA, Skinner JA, Goldfine H, Shen H (2004) Listeria monocytogenes virulence proteins induce surface expression of Fas ligand on T lymphocytes. Mol Microbiol 51:1483–1492PubMedCrossRefPubMedCentralGoogle Scholar
  93. Zenewicz LA, Wei Z, Goldfine H, Shen H (2005) Phosphatidylinositol-specific phospholipase C of Bacillus anthracis down-modulates the immune response. J Immunol 174:8011–8016PubMedCrossRefPubMedCentralGoogle Scholar
  94. Zückert WR, Marquis H, Goldfine H (1998) Modulation of enzymatic activity and biological function of Listeria monocytogenes broad-range phospholipase C by amino acid substitutions and by replacement with the Bacillus cereus ortholog. Infect Immun 66:4823–4831PubMedPubMedCentralGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of MicrobiologyPerelman School of Medicine of the University of PennsylvaniaPhiladelphiaUSA

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